Healthcare Professional Question Database

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Date Question  
Jan. 31, 2017What is the safety profile of Estrosmart? details
 

Response: The recommended dose by the manufacturer is 4 capsules per day. If taking 4 capsules of Estrosmart daily, the intake will include:
3,3'-Methylenebis-1H-indole (common name = indole-3-carbinol [I3C]): 100 mg
3-Hydroxymethylindole (common name = diindolylmethane [DIM]): 300 mg
Broccoli: 400 mcg
Green Tea (50% EGCG, no caffeine): 200 mg
Turmeric: 100 mg
Calcium D-glutarate 300 mg
Rosemary 50 mg

Safety with respect to dose/amount of each active ingredient:
The only evidence of broccoli is from dietary intake so there is no relevant safety information. No dosing recommendations are available for calcium-D glutarate.(4)
Some evidence suggests doses of I3C <200 mg daily can be used safely for up to 15 months.
Two studies have looked at DIM: the first used 2 mg/kg/day x 12 weeks with no problem.(1) The 2nd was a dose escalation study starting at 75 mg PO BID and ending with 300 mg PO BID.(2) Adverse effects were mild, though 2 of 4 patients taking 300 mg BID developed asymptomatic hyponatremia. As such, 225 mg PO BID was considered the appropriate dose for phase II trials; the amount in estrosmart is well below this amount.
The amounts of turmeric and rosemary in the recommended daily dose are much lower than usual doses (1g daily and 4-6g daily, respectively).(4)
Similarly with green tea, products tend to provide 75-400 mg epigallocatechin-3-gallate EGCG daily; this product’s EGCG content is 25 mg (50%). (4)
Adverse Effects(4)
The ingredients are well-tolerated.(4) Rash has been reported following I3C. Note the asymptomatic hyponatremia discussed above with DIM. Gastrointestinal adverse effects such as dyspepsia, diarrhea, and GERD have been associated with turmeric, though the low dose in this product will likely reduce incidence of these. Most adverse effects of green tea are on account of the caffeine content and this product is caffeine-free. No general adverse effects are documented for calcium-D glutarate or rosemary.
Interactions (4)
Due to the potential hyponatremic effect of DIM, use with caution in combination with diuretics or other drugs that can cause/exacerbate hyponatremia. Green tea (catechins), turmeric, and rosemary potentially have anticoagulant/antiplatelet effects. The interactions are theoretical, and this product contains very low doses of these ingredients, so they may not be as great of a concern. Green tea and rosemary may reduce absorption of dietary iron; the one study incorporated the extracts into the food and seems to exert the effect on release of heme-iron from the food.(3) Theoretically calcium-D glutarate may increase the clearance of drugs that undergo glucuronidation (e.g. acetaminophen, atorvastatin, diazepam, digoxin, lamotrigine, lorazepam, lovastatin, morphine, oxazepam).
Efficacy
The effectiveness of these ingredients has been made by extrapolating in vitro data.
References: 1.Del Priore G., Gudipudi, D. K., Montemarano, N., Restivo, A. M., Malanowska-Stega, J., and Arslan, A. A. Oral diindolylmethane (DIM): pilot evaluation of a nonsurgical treatment for cervical dysplasia. Gynecol.Oncol. 2010;116(3):464-467.
2.Heath, E. I., Heilbrun, L. K., Li, J., Vaishampayan, U., Harper, F., Pemberton, P., and Sarkar, F. H. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3'- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am.J.Transl.Res. 2010;2(4):402-411.
3.Samman S, Sandstrom B, Toft MB, et al. Green tea or rosemary extract added to foods reduces nonheme-iron absorption. Am J Clin Nutr 2001;73:607-12.
4. Ulbricht K, Basch E, editors. Online Natural Medicines[Internet]. Somerville (MA); c2017 [cited 14 Feb 2017]. Available from: https://naturalmedicines.therapeuticresearch.com/ Subscription required.

Feb. 8, 2017What are some potential reasons why phenytoin levels may increase or decrease? What is the best way to achieve a dose between 300mg-400mg daily using the 100mg capsules only? details
 

Patient Age: 83
Patient Sex: M
Medical Problems: Seizure disorder - last documented seizure 4 years ago
Serum albumin: 35 g/L
Total phenytoin: 30 umol/L
Medication History: Dilantin capsules 300 mg daily
spironolactone, furosemide, venlafaxine, warfarin, lorazepam
Response: Some potential factors causing reduced phenytoin levels might include (3):
- non-adherence
- ethanol intake; while it is thought acute heavy intake of ethanol will cause enzyme inhibition (and potentially increased phenytoin levels), this was not demonstrated in a single-dose kinetic study. (5) In terms of reduced levels, a kinetic study has demonstrated patients who drink at least 200g ethanol daily require higher phenytoin doses to maintain the same serum concentrations as non-drinkers. (5) However, this would mean the patient just recently started drinking heavily (upwards of 14 drinks per day) (6) on a daily basis.

Every other day dosing such as 300 mg alternating with 400 mg is a viable option.(4) As an alternative, give 3 x 400 mg doses per week on M, W, F with 300 mg given on the remaining days. A Monday morning trough level should give the trough of the whole week (since it's the only day with two consecutive days of 300 mg doses).
References: 1. http://www.globalrph.com/conv_si.htm#Parathyroid
2. http://clincalc.com/phenytoin/correction.aspx
3. http://mentalhealth.com/home/rx/phenytoin.html
4. Bauer LA. Phenytoin/Fosphenytoin. In: Bauer LA. eds. Applied Clinical Pharmacokinetics, 3e. New York, NY: McGraw-Hill; 2015. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1374§ionid=74720536. Accessed February 09, 2017.
5. Stockley's
6. https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/what-standard-drink

Feb. 8, 2017What is the dosing regimen for amoxicillin, omeprazole, and clarithromycin for treating H. pylori in a child? details
 

Patient Age: 10
Medical Problems: H Pylori
Response: Amoxicillin:
25 mg/kg BID (max 2000 mg per day) (1,3)
Clarithromycin:
7.5 mg/kg BID (1) or
10 mg/kg BID (max 500 mg) (3)
Omeprazole:
0.5-1 mg/kg BID (max 20 mg) (1,3)
Best to treat children for 14 days. (2)
References: 1) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724145/table/t3-pch09709/
2) http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Hpylori.pdf
3) Lexi-peds

Feb. 8, 2017How do you treat arthritic pain in a hemochromatosis patient who has a contraindication for medications extensively metabolized by the liver (such as acetaminophen)? Would Gabapentin be a potential option? details
 

Patient Age: 58
Patient Sex: F
Medical Problems: hemochromatosis - told to avoid APAP but has not been told has any actual liver disease/damage
Response: Arthropathy is a common manifestation of hemochromatosis (HC) (1,4,12,13) that is generally not relieved by phlebotomy. (2, 6,12,13,15,16) The only information regarding treatment are statements in review articles in which options for arthritis are considered: NSAIDs (2,6,15) and intra-articular glucocorticosteroids (2,6,15,16). Colchicine may be used acutely as well if the cause of pain is seemingly pseudogout (6,15), and possibly at low dose for maintenance. (2,15,16) Short term systemic steroids are also considered. (2) APAP was only specifically listed in one paper, (15) though other papers refer to use of usual analgesics in general. (2,6,16) Toxicity from APAP occurs when there is not enough glutathione to bind to the intermediate and toxic metabolite, NAPQI. (8) Nothing directly states that APAP should not be used in HC; however, some preliminary research in animals suggests APAP toxicity may be potentiated by higher iron levels. (11) A clinical trial of anakinra for HC arthritis requires patients to have used and failed/not tolerated at least one month of maximal dose weak opioids, NSAID, colchicine, steroid injection, or a combination of the treatments. (13)
As for gabapentin, considering these are arthropathies, neuropathic agents would not be expected to be effective; there was no mention of use of neuropathic agents in any of the readings.
Therefore, if the arthropathy is akin to pseudogout, colchine would be reasonable for both acute attacks and long term. Also considered for acute attacks can be NSAIDs and intra-articular steroid injections. For non-pseudogout arthropathy, NSAIDs, intra-articular steroid injections (if confined to minimal joints), or short-term systemic steroids may be possibilities. Certainly each of these can cause long-term adverse effects; the lowest possible dose taken as infrequently as possible should be used.
References: 1. UTD - Clinical manifestations and diagnosis of hereditary hemochromatosis
2. UTD - Rheumatic manifestations of hereditary hemochromatosis
4. Lawrie PW. Hemochromatosis. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e. New York, NY: McGraw-Hill; 2015. http://accessmedicine.mhmedical.com/content.aspx?bookid=1130§ionid=79754178. Accessed February 08, 2017.
6. https://www.hindawi.com/journals/arthritis/2014/375202/
7. https://gi.org/guideline/diagnosis-and-management-of-idiosyncratic-drug-induced-liver-injury/
8. http://emedicine.medscape.com/article/169814-overview#showall
11. https://academic.oup.com/toxsci/article/118/1/119/1661933/Iron-Potentiates-Acetaminophen-Induced-Oxidative
12. http://www.academia.edu/17265556/Arthritis_of_hemochromatosis
13. https://clinicaltrials.gov/ct2/show/NCT02263638
15. http://www.physicianspractice.com/articles/identifying-and-managing-hemochromatosis-arthropathy
16. Miscellaneous non-inflammatory musculoskeletal conditions. Haemochromatosis: the bone and the joint. Guggenbuhl P, Brissot P, Loréal O. Best Pract Res Clin Rheumatol. 2011 Oct;25(5):649-64. doi: 10.1016/j.berh.2011.10.014. Review. PMID: 22142745

Feb. 9, 2017If a patient has experienced anaphylactic reaction to ibuprofen in the past and has now been prescribed sulfasalazine, is there a potential for a cross-reaction? details
 

Response: There has only been one case report of sulfasalazine use in a patient with reported NSAID (ibuprofen) allergy.(4) Unfortunately, the details of the reported allergy were not documented and the child was not provided a challenge dose of sulfasalazine, rather they pre-emptively desensitized; as such, it cannot be known if the child would have also reacted to a therapeutic dose of sulfasalazine.(4) Considering ASA/NSAID reactions are related to COX inhibition, subsequent release of histamine, and synthesis of leukotrienes, a mechanistic phenomenon that has not been observed with 5-ASA is by inhibiting prostaglandin E2 and leukotrienes. (4) Furthermore, if this were a true IgE mediated reaction, it is specific to ibuprofen. (4,5) However, because the absence of reports does not prove it is not possible, to be prudent, a supervised test dose is a reasonable strategy. (4,5)
References: 4. Poh J, Knowles S. Safety of 5-Aminosalicylic Acid Derivatives in Patients with Sensitivity to Acetylsalicylic Acid and Nonsteroidal Anti-inflammatory Drugs. The Canadian Journal of Hospital Pharmacy. 2014;67(1):35-38. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3952906/
5. https://www.aaaai.org/ask-the-expert/mesalamine-nsaid

Feb. 9, 2017Is Cymbalta a good choice for treating anxiety with concurrent chronic pain in multiple sites? details
 

Patient Sex: F
Medical Problems: chronic pain
anxiety
Response: There is some literature of duloxetine in adolescents and pieced together, it seems a reasonable agent to trial.
Three fairly large trials have been conducted in adolescents for the treatment of depression. (6,8,9) These trials used placebo and fluoxetine comparators, included over 1000 adolescents (n=476 received duloxetine, n= 234 received fluoxetine) and assessed efficacy, safety, and pharmacokinetics.
Pharmacokinetics: conclusions from the study in 72 children between the ages of 7 and 17 were that "adjustment of total daily dose based on body weight or age is not warranted for pediatric patients, and different total daily doses may not be warranted for pediatric patients relative to adults." (6)
In terms of safety: no changes in ECG (8), blood pressure (9) or laboratory abnormalities were identified. (8,9) Pulse did increase on average 4 bpm in the duloxetine group compared to a reduction of 1.3 bpm in the fluoxetine group in the second trial. (9) Furthermore, a total of five patients in the duloxetine group sustained elevations in blood pressure compared to none in the fluoxetine group. (9) No differences in suicidal ideation (9) or worsening suicidal ideation (8) were reported compared to placebo. (8) However, in the first study, 2.7% in the duloxetine compared to 0.9% and 0.8% in the fluoxetine and placebo groups, respectively, had treatment-emergent suicidal behaviour during the 36 week study; (8) no differences were found in the second study. (9) Treatment-emergent adverse effects (not detailed) and drop outs due to adverse effects occurred more frequently in the duloxetine 60 mg group, but not the duloxetine 30 mg group in the first trial. (8) Conversely, no differences in these outcomes were reported in the second trial. (9)
In terms of efficacy: neither duloxetine nor fluoxetine demonstrated effectiveness compared to placebo. (8) However, keep in mind these trials were in pediatric depression. One trial in generalized anxiety has been conducted that enrolled 272 youth aged 7 through 17 years (n=135 duloxetine). (7) This trial included a 10 week placebo-controlled phase followed by an 18 week open-label extension. Following the first 10 weeks, duloxetine demonstrated a statistically significant improvement in GAD compared to placebo. This trial was designed for flexible dosing (30 mg-120 mg daily); the mean dose in the acute phase was 53.6 mg and 63.2 mg in the extension phase.
There appear to be no trials assessing the use of duloxetine for pediatric pain. Three case reports are available in which duloxetine (final doses of 40 mg (4) and 60 mg (5)) seemed to provide significant benefit for pain in a 13(4), 14(4) and 10 year old(5), respectively.
References: 1. UTD - Evaluation and management of pain in children
2. UTD - Pharmacotherapy for anxiety disorders in children and adolescents
3. UTD - Pediatric unipolar depression and pharmacotherapy: Choosing a medication
4. Meighen KG. Duloxetine treatment of pediatric chronic pain and co-morbid major depressive disorder. J Child Adolesc Psychopharmacol 2007; 17:121. PMID 17343560
5. Desarkar P, Das A, Sinha VK. Duloxetine for childhood depression with pain and dissociative symptoms. Eur Child Adolesc Psychiatry 2006; 15:496. PMID 16732464
6. Clin Pharmacokinet. 2014 Aug;53(8):731-40. doi: 10.1007/s40262-014-0149-y. Pharmacokinetics of orally administered duloxetine in children and adolescents with major depressive disorder. Lobo ED1, Quinlan T, Prakash A. PMID 24989060
7. Strawn JR, Prakash A, Zhang Q, et al. A randomized, placebo-controlled study of duloxetine for the treatment of children and adolescents with generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry. 2015 Apr;54(4):283-93. doi: 10.1016/j.jaac.2015.01.008. Epub 2015 Jan 29. PMID 25791145
8. Emslie G, Prakash A, Zhang Q, et al. A double-blind, efficacy and safety study of duloxetine fixed doses in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014;24(4):170–9.
9. Atkinson SD, Prakash A, Zhang Q, et al. A double-blind, efficacy and safety study of duloxetine flexible dosing in children and adolescents with major depressive disorder. J Child Adolesc Psychopharmacol. 2014;24(4):180–9.

Feb. 9, 2017What are potential iatrogenic causes of anisocoria? details
 

Medical Problems: diffuse large B cell lymphoma
anisocoria x couple of months (may have been just noticed today)
atrial fibrillation
propranolol --> metoprolol Feb 2
loperamide new
apixaban --> Jan 17
a fib (relatively recent diagnosis)
Medication History: tazocin (feb 3), Vancomycin (Feb 7)
alendronate/Vit D weekly, apixaban (started Jan 17), Dilaudid, folic acid, metoprolol(switched from propranolol Feb 2), mirabegron 50 mg, pantoprazole, perindopril, prednisone 10 mg od, pregabalin
PRNs: APAP (none recently), dimenhydrinate, Buscopan (just started today), loperamide (had a few doses post-chemo), lorazepam, metoclopramide, Zofran
Post archop (day 22)
Response: Drug-induced anisocoria has been reported, and it is often due to anticholinergic drugs. (3,4,6) Most cases follow direct contact with the eye (3,14), such as removing a scopolamine patch and touching the eye (9,11) or several cases of misdirected ipratropium nebulization contacting one eye only. (7,10,12) There is one case in which perioperative systemic anticholinergic administration of IV butylscopolamine appeared to be the cause of anisocoria; though the author of this report was unsure as to why only one pupil had been dilated, not both. (13)
If the anisocoria occurs more in light environments, the large pupil is abnormal; if no ptosis/ophthalmoplegia, application of graded pilocarpine to the dilated eye can help confirm pharmacological causes. The recommendation is to use 0.1% first, and if there is no constriction, apply 1%. If there is still no or minimal constriction, it is likely pharmacological anisocoria. (3,14)
References: 1. http://sideeffects.embl.de/se/C0003079/
2. DrugDex
3. UTD - Approach to the patient with anisocoria
4. http://emedicine.medscape.com/article/1158571-clinical#b5
6.https://www.google.com/url?q=http://www.aaopt.org/sites/default/files/userfiles/outlines/outline25402.DOC&sa=U&ved=0ahUKEwj92cKmlobSAhUE2WMKHT94DxM4FBAWCBMwBw&client=internal-uds-cse&usg=AFQjCNENOjWGtTI55L_Zg6dxTwfZCm05zA
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3159376/
9. Acute pupil asymmetry in a 6-month-old boy. Diagnosis: pharmacologic anisocoria. Osorio MJ, Zuckerbraun NS, Painter M. Pediatr Ann. 2009 Nov;38(11):622-4, 627. doi: 10.3928/00904481-20091016-07. No abstract available. PMID: 19968207
11. Transdermal scopolamine and perioperative anisocoria in craniofacial surgery: a report of 3 patients. Lee DT, Jenkins NL, Anastasopulos AJ, Volpe AG, Lee BT, Lalikos JF.
J Craniofac Surg. 2013 Mar;24(2):470-2. doi: 10.1097/SCS.0b013e318275ec4a. PMID: 23524718
12. PubMed: "anisocoria anticholinergic"
13. Transient anisocoria after intravenous administration of butylscopolamine. Kiyama S. Anesth Analg. 1991 Jul;73(1):97-8. No abstract available. PMID: 1859001
14. Anisocoria after open reduction and internal fixation of a mandible fracture under general anesthesia: a case report. Jarmoc M, Shastri K, Davis F. J Oral Maxillofac Surg. 2010 Apr;68(4):898-901. doi: 10.1016/j.joms.2009.02.010. No abstract available. PMID: 20022156

Feb. 10, 2017Zoloft is contraindicated in those with closed-angle glaucoma. Are there any other safer SSRIs for use in patients with CAG? details
 

Medical Problems: closed-angle glaucoma
hyperthyroidism
Response: SSRIs/SNRIs appear on lists of drugs that can exacerbate CAG.(1,2) One article suggests it is due to anticholinergic properties.(2) Antidepressants without anticholinergic activity include bupropion, trazodone, venlafaxine, fluvoxamine, sertraline(3) though they all have a warning to evaluate patients for narrow-glaucoma if they have not had an iridectomy. (4)
More information is required. If the patient is at risk of CAG or for some reason the patient has CAG but cannot have surgery or patient is waiting for surgery, buprioprion may be suggested as it was not included in the lists of antidepressants associated with CAG close monitoring. (1, 2)
References: 1. UTD - Angle-closure glaucoma Table - Medications associated with acute angle-closure glaucoma (AACG)
2. A review of drug-induced acute angle closure glaucoma for non-ophthalmologists. Ah-Kee EY, Egong E, Shafi A, Lim LT, Yim JL. Qatar Med J. 2015 May 10;2015(1):6. doi: 0.5339/qmj.2015.6. Review. PMID: 26535174
3. Clinical Handbook of Psychotropic Drugs, pg 60
4. Lexicomp

Feb. 10, 2017We have rx for nitrofurantoin for a breastfeeding woman with UTI. My research suggests nitrofurantoin may be of concern. Is there any more data? What alternatives are available. details
 

Medical Problems: infant = 10 days old, 5 days out of NICU
NKA
maternal UTI
Medication History: nothing, no antibiotics in last year
Response: While it appears nitrofurantoin may be safe for maternal use in breastfeeding infants at least 8 days' old (1), this infant is just on the cusp and spent his first 5 days in NICU. Based on information below, consider trimethoprim alone or cephalexin.

Alternatives and safety in nursing:
Fosfomycin is 1st line, (2,3) however, due to limited information about use in breastfeeding infants, it is considered to be “likely safe,” especially if infant is 2 months old. (1)
Cephalexin is an alternative for 1st time cystitis with no antibiotic exposure in the last 6 months. (2) There are low levels detected in breastmilk, but it can possibly cause diarrhea/thrush in the breastfeeding infant. (1,3)
TMP/SMX is an alternative for 1st time cystitis and no antibiotic exposure within last 6 months. (2) It is acceptable after the newborn period (i.e. 1 month of age). (1)
Ciprofloxacin is an alternative for 1st time cystitis and no antibiotic exposure within last 6 months. (2)It is traditionally not used because of concerns regarding infant joint development. It's possible the calcium in the breastmilk may bind ciprofloxacin, thereby reducing exposure to the infant. Use in nursing mothers is acceptable with monitoring of the infant for diarrhea or thrush, and avoiding breastfeeding for 3-4 hours after a dose to decrease the exposure. (1)
Trimethoprim is found in low levels in breastmilk; it is not a concern.(1,3)
References: 1. Lactmed
2. Bugs and Drugs app
3. MUMS app

Feb. 10, 2017My patient with MS (who takes Tecfidera) is wondering if it's safe to use CBD hemp oil. details
 

Patient Age: 41
Patient Sex: F
Medical Problems: M.S.
Anxiety
stomach problems
Medication History: Tecfidera
Response: Currently, there is no evidence for a drug-drug interaction between Tecfidera and hemp oil. (1,2,3). Potentially an interaction could occur and hemp oil should be used with caution. Tecfidera causes immunosuppression and hemp oil studies in mice have also shown some immunosuppressive properties. (2) Therefore we may suspect potentially greater immunosuppression with the combination. Safety data currently says hemp oil use is likely safe in adults, but there is no evidence to suggest efficacy in treating any condition. (2) There may be greater risk than benefit in this case. Depending on what the hemp oil is being used for, it may be more appropriate to consider alternative therapy.
References: 1. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 13 Feb 2017
2. Ulbricht K, Basch E, editors. Online Natural Medicines[Internet]. Somerville (MA); c2017 [cited 13 Feb 2017]. Available from: https://naturalmedicines.therapeuticresearch.com/ Subscription required.
3. Ogbru O, Abedin S, editors. RxList. San Clemente, CA: WebMD; c2017 [cited 13 Feb 2017]. Available from: http://www.rxlist.com

Feb. 10, 2017My patient would like information on treatment options for primary progressive multiple sclerosis, including ocrelizumab, and stem cell transplant information. details
 

Patient Age: 37
Patient Sex: M
Medical Problems: primary progressive multiple sclerosis dianosed last year
Medication History: n/a
Response: Primary progressive MS lacks effective medical treatment, potentially due to the absence of inflammation, unlike relapsing MS (1). There are currently no approved medications for PPMS however some medications have shown potential including methotrexate, rituximab, ocrelizumab, and stem cell therapy. (2, 3)

A. Methotrexate has ambiguous evidence for use in PPMS and evidence stems from a single RCT. (4, 5, 6) Based on the single RCT, it is possible that methotrexate may slightly improve the disease course of PPMS through alteration of the immune system. (5, 7) However a Cochrane review, limited to the single RCT, concluded that there was a non-significant trend in reducing disability progression and number of relapses. (7) More research needs to be completed to determine if the efficacy of methotrexate in PPMS outweighs its side effects.

B. Rituximab may delay disease progression in patients less than 51 years old with PPMS. (3) The examination of rituximab in MS is referred to as the OLYMPUS trial and a subgroup analysis of patients less than 51 years old showed a delay in confirmed disease progression. (8) The proportion of patients with confirmed disease progression at 96 weeks was 30.2% rituximab vs. 38.5% placebo (rituximab n= 272 vs placebo n= 147). (4, 8)

C. Ocrelizumab is the first drug to show a significant reduced risk of disability progression among patients with PPMS as in the ORATORIO trial. The trial has shown modest reduction of disability progression (ARR 6% at 12 and 24 weeks, compared to placebo), slowed deterioration from baseline of a timed 25-foot walk, and improvements in MRI T2 lesion volume and whole brain volume loss. Compared to placebo, Ocrelizumab has been associated with more neoplasms, infusion reactions, upper respiratory tract infections, and oral herpes. (9) Ocrelizumab is not currently available in Canada and a phase 3 trial is expected to finish in 2021. (10)

D. Stem cell therapy has been used experimentally in those with aggressive or unresponsive MS. It has shown some evidence slowing MS disease activity and repairing damage in the CNS. However stem cell therapy has been shown to increase mortality by 1-2%. The procedure includes collecting patient stem cells followed by exposure to chemotherapy to deplete the immune system, as immune system dysfunction is thought to be causing the MS damage. There is currently no approved stem cell therapy treatment for MS and there needs to be further analysis on the risks vs benefits of SC treatment. (11)

Impairment due to MS, such as spasticity, mobility, tremor, pain, fatigue, urinary symptoms, depression, and anxiety may be managed through nonpharmacological and pharmacological therapy when needed. (3)
References: References:
1. MS Society of Canada. Progressive MS.[homepage on the internet] Toronto Ont: MS Society of Canada; [updated NA; cited 2017 Feb 13] Available from : https://mssociety.ca/hot-topics/progressive-multiple-sclerosis
2. Hoffman La-Roche. Media release: FDA extends review of application for OCREVUS [homepage on the internet]. Switzerland, Hoffmann La-Roche; [updated NA; cited Feb 13, 2017]. Available from: http://www.roche.com/media/store/releases/med-cor-2016-12-20.htm
3. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 116285, Multiple sclerosis (MS); [updated 2017 Jan 27, cited Saskatoon, Feb 13 2017]; [about 35 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116285&site=dynamed-live&scope=site. Registration and login required.
4. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 905968, Disease-modifying therapies for multiple sclerosis; [updated 2017 Feb 03, cited Saskatoon, Feb 13 2017]; [about 29 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=905968&site=dynamed-live&scope=site. Registration and login required.
5. Goodin D, Frohman E, Garmany G, Halper J, Likosky W, Lublin F et al. Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology. 2002;58(2):169-178.
6. Goodkin DE, Rudick RA, VanderBrug Medendorp S, Daughtry MM, Schwetz KM, Fischer J, Van Dyke C. Low dose (7.5mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Annals of Neurology 1995;37:30-40
7. Gray O, McDonnell GV, Forbes RB. Methotrexate for multiple sclerosis. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD003208. DOI: 10.1002/14651858.CD003208.pub2
8. Hawker K, O'Connor P, Freedman M, Calabresi P, Antel J, Simon J et al. Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Annals of Neurology. 2009;66(4):460-471.
9. Olek, Michael J. Treatment of progressive multiple sclerosis in adults. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 13 Feb 2017. Available from www.uptodate.com. Subscription and login required
10. Clinicaltrials.gov. A study of ocrelizumab in participants with primary progressive multiple sclerosis [homepage on the internet]: Bethesda, MD: Clinicaltrials.gov. [updated Jan 6 2017: cited Feb 13 2017]. Available from: https://clinicaltrials.gov/ct2/show/study/NCT01194570?term=ocrelizumab&rank=6&show_locs=Y#locn
11. MS Society of Canada. Stem Cells. [homepage on the internet]. Toronto Ont: MS Society of Canada; [updated NA; cited 2017 Feb 13] Available from: https://mssociety.ca/hot-topics/stem-cells

Feb. 10, 2017If a patient has failed to have clinical success on a 10-day course of amoxicillin for Scarlet fever, and erythromycin is unavailable as an alternative, what may be some other alternative options for therapy? details
 

Patient Sex: 5
Medical Problems: NKA
no meds
20.8 kg
Medication History: Amoxicillin x 10 days, rash, sore throat persist
Response: While there would be no reason to continue treatment based on the rash alone (1), considering the continued presence of sore throat, further treatment may be warranted. Azithromycin and clindamycin are alternative treatments (2) though resistance is consdierable in Canada.(3) Cephalopsorins are also an alternative, but considering it is another beta-lactam, it may not be the best choice.
Suggest
Azithromycin 20 mg/kg/d x 3 days (2,3) or 12 mg/kg.d x 5 days (2,4)
Or
Cephalexin 25-50 mg/kg/day div QID or cefuroxime-AX 20 mg/kg/day divied BID x 10 days (4)
References: 1. UTD - Complications of streptococcal tonsillopharyngitis
2. UTD - Treatment and prevention of streptococcal tonsillopharyngitis
3. Bugs and Drugs
4. MUMS app

Feb. 13, 2017Can pregabalin or gabapentin be used in a patient on peritoneal dialysis (eGFR 5-7 ml/min)? details
 

Medical Problems: GFR 5-7 ml/min
Response: For both pregabalin and gabapentin, patients on peritoneal dialysis should be dosed as though CrCl < 15 ml/min.(4) Starting doses of gabapentin 50-100 mg once daily (1,2,4) or 25 mg pregabalin (1,2,4) once daily would be appropriate. Suggested maximum dose of pregabalin is 75 mg once daily. (1,2)
References: 1. Lexicomp
2. DrugDex
3. Dialysis of Drugs 2013
4. Renal Drug Handbook

Feb. 13, 2017My patient received a prescription for metoprolol 25 mg PO BID for benign PVCs. I am unsure if the cardiologist is aware her resting HR is 50-55 and resting BP is 112/68. Will metoprolol further reduce her HR and BP, making her feel worse? She also takes Neo-40, a natural product formulated of nitric oxide. Could it be contributing to her low HR and BP? details
 

Medical Problems: PVCs - not bothering her went on antibiotic in December and they flared, then resolved after antibiotic was stopped
Medication History: Pantoloc, zopiclone, premarin cream, Flonase, Ditropan
Response: The main treatment for PVCs is treating the underlying structural heart disease/ symptoms, if present.(1) For those with no structural disease but bothersome symptomatic PVCs, beta blockers may be useful, though have not been shown to improve survival in this population.(1) Certainly beta blockers can be expected to reduce heart rate(2,3), though this is less pronounced with beta blockers with ISA;(2) Metoprolol is not ISA positive.(3)
The formulation of Neo 40 is only available on the website as a 'patented formula' with Vitamin C and Vitamin B12.(4) One of the referenced studies included ingredients: beet root extract, hawthorn berry, vitamin C, L-citrulline, and sodium nitrite.(6) Hawthorn berry and L-citrulline theoretically can cause additive hypotension (7); however, the only ingredient that has any sort of evidence is hawthorn berry (it may be possibly effective for angina and HF).(7) One small pilot trial suggests the product may lower BP more than placebo with no change in heart rate, though the methodology is weak to make any firm conclusions. (5)
Therefore, it is possible the Neo40 is contributing to lower blood pressure. The metoprolol is likely to further reduce heart rate and it seems important to clarify if the cardiologist is aware of the patient's resting HR.
References:
1. UTD - Ventricular premature beats
2. UTD - Major side effects of beta blockers
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-HTN-bb.pdf
4. http://neogenis.ca/#/faq
5. http://neogenis.ca/articles/Prehypertension-Clinical-Trial.pdf
Biswas O, et al. Effects of an Oral Nitric Oxide Supplement on Functional Capacity and Blood Pressure in Adults With Prehypertension. J Cardiovasc Pharmacol Ther. 2014
6. http://neogenis.ca/articles/JCH%20final%20proofs.PDF
Houston M, et al. Acute Effects of an Oral Nitric Oxide Supplement on Blood Pressure, Endothelial Function, and Vascular Compliance in Hypertensive Patients. J Clin Hyper. 2014
7. Natural Medicines

Feb. 14, 2017Is a washout period required when switching from Neupro patch to ropinirole? details
 

Patient Age: 64
Medication History: levocarb, amantadine
Response: Most studies address the switch from oral treatment to the patch. (2-4) While there was no report of how patients tolerated the switch, one study employed an overnight switch with patients changing from rotigotine patch to oral ropinirole or oral pramipexole.(5) Those switching to ropinirole did so at a 1:1 dose conversion.(5) This seems reasonable given the plasma levels decrease with a terminal half-life of 5-7 hours following patch removal.(1)
References: 1. eCPS - Neupro
2. Winkelman JW, Mackie SE, et al. A method to switch from oral dopamine agonists to rotigotine in patients with restless legs syndrome and mild augmentation. Sleep Med. 2016 Aug;24:18-23.
3. Kim HJ, Jeon BS, Lee WY, et al. Overnight switch from ropinirole to transdermal rotigotine patch in patients with Parkinson disease. BMC Neurol. 2011 Aug 10;11:100.
4. eWitt PA, Boroojerdi B, MacMahon D, et al. Overnight switch from oral dopaminergic agonists to transdermal rotigotine patch in subjects with Parkinson disease. L
Clin Neuropharmacol. 2007 Sep-Oct;30(5):256-65.
5. Chitnis S, Jaffery M, Dewey RB.Outcomes from switching from rotigotine patch to alternate therapies in Parkinson's disease. Int J Neurosci. 2012 Jan;122(1):22-5.

Feb. 14, 2017Are there any contraindications to give emergency contraceptive pills in a patient who has a copper IUD? details
 

Response: There are no contraindications to give ECP in the presence of a copper IUD. (1) It is likely not required in this case as copper IUDs are also used as a form of emergency contraception and are more effective than hormonal emergency contraception. (1) Educating the patient on the role of copper IUDs for emergency contraception may help reduce their anxiety.
References: 1. SOGC - Emergency Contraception 2012

Feb. 14, 2017My patient’s cardiologist prescribed dabigatran 110 mg BID as they are experiencing symptoms of atrial fibrillation again after being cardioverted 10 years ago. My software says verapamil (and theoretically diltiazem) increases dabigatran levels, what is the significance of this? My patient also has a history of GI bleeds (currently on pantoprazole) so increased dabigatran levels is concerning. details
 

Patient Age: 64
Patient Sex: M
Medical Problems: atrial fibrillation - converted 10 years ago, symptoms recurring
(has been to many specialists and had surgeries over the years)
hx GI bleed -
normal renal function
Medication History: diltiazem 30 mg up to TID, depending how feels (see notes in med problems)
furosemide, opioids, pantoprazole, zopiclone, trazodone, levothyroxine
T3, hydromorphone
topical testosterone
Response: Documentation of elevated dabigatran levels secondary to verapamil exists(1); despite this, no dose adjustment is recommended.(2) There is no documentation of the interaction with diltiazem.(1) It appears the MD has considered patients bleed risk and reduced dose to 110 mg po BID as suggested in the monograph (2). Pantoprazole, which not only acts as a gastic protectant, may actually reduce dabigatran levels, however no dose adjustment is recommended.(2) Considering all of these factors, the risk of bleeding does not appear to outweigh the anticoagulant benefits.
References: 1. Stockley's
2. eCPS - Pradaxa

Feb. 14, 2017I have a patient who takes up to 40 mg per day of ondansetron due to nausea associated with anxiety. Other than ECG changes and risk of serotonin syndrome, is there any information on the safety of long term ondansetron overuse? details
 

Response: Oral ondansetron is typically used for chemotherapy-induced nausea and vomiting at the dose of 8 mg PO twice daily for 3 days and highly emetogenic chemo has been dosed up to 24 mg PO 30 minutes before starting treatment. (1) Acute overdose of ondansetron has caused fever, rash, pruritus, restlessness, CNS depression, seizures, tachycardia, elevated liver enzymes, hypotension and temporary blindness. (1) Ondansetron, as a serotonergic agent, is also known to cause agitation (oral: ≤6%) and anxiety (oral: ≤6%). (2)
One case study describes a 25 year old man taking up to 40 x 4 mg ondansetron tablets per day for a week for nausea and vomiting following gastric bypass. The patient was admitted with severe headache of a week’s duration and imaging showed acquired cerebral edema, later experiencing near blindness and an intracranial hemorrhage. In this case it was recognized as posterior reversible encephalopathy syndrome which describes changes in neuroimaging potentially due to impaired cerebral blood flow and endothelial dysfunction. (3)
No human data is available regarding potential cumulative effects of chronic use of high dose ondansetron. The monograph describes animal studies in which dogs given oral ondansetron, at 7.5-25 mg/kg/day for 5 weeks, exhibited behavioral depression (at highest dose levels). In rats and mice, there was no evidence of tumourgenic effects with high-dose ondansetron taken for 2 years. (4)
Overall, there is limited safety evidence for chronic high dose ondansetron use.
References: 1. DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: Feb/14/2017).
2. Lexi-Comp OnlineTM , Lexi-DrugsTM , Ondansetron, Hudson, Ohio: Lexi-Comp, Inc.; 2017; February 14, 2017.
3. Toxnet Toxicology Data Network. Hazadrous Drugs Data Base (HSBD) [homepage on the Internet]. Ondansetron. Bethesda, MD: U.S. National Library of Medicine; [updated 2016 Oct 25; cited 2017 Feb 14]. Available from: https://toxnet.nlm.nih.gov/cgi-bin/sis/search2/f?./temp/~GsRvmM:3
4. Product Monograph (not online). Product monograph for Ondansetron. Actavis Pharma Company. Mississauga, ONT. L5N 6J5. February 2017.

Feb. 16, 2017What is unfractionated heparin? details
 

Response: Unfractionated heparin is the same as heparin (1). It is unlike low molecular weight heparins which would be ordered as the brand (eg. Innohep) or generic name (eg. tinzaparin).
References: 1. eCPS - CPhA Heparin: Unfractionated

Feb. 16, 2017Is a taper required for this prescription: Prednisone 50 mg po OD for 10 days? details
 

Medical Problems: Language barrier but caller thinks a TB treatment protocol caused something with platelets
Response: Risk of adrenal suppression (nausea, fatigue, shortness of breath, hypotension, hypoglycemia, myalgia, fever, dizziness) is low if systemic steroids are taken less than 3 weeks. (1,2,3) One may want to consider a short tapering course if there is risk of disease flare (e.g. autoimmune, poison ivy), or patient is ill or frail.(1,2,3)
References: 1. Canadian Pharmacist's Letter 2010; 26(5):260507
2. https://aacijournal.biomedcentral.com/articles/10.1186/1710-1492-9-30
3. eCPS - CPhA Monograph - Corticosteroids: Systemic
4. GeriRx Files, pg 178

Feb. 16, 2017Are there any drug interactions or generally harmful contents in this product? Any concerns with use in a patient with coronary artery disease? Product in question contains (serving size per 4 capsules): A. Proprietary testosterone support complex 2.1 g [containing Testofen - Trigonella foenun greacum (fenugreek) seed, Trigotest - Trigonella foenun greacum (fenugreek) seed, and Tribulus.] B. Proprietary DHT support complex 280 mg [containing saw palmetto extract, stinging nettle] C. Proprietary estrogen support complex 150 mg [containing hesperidin, apigenin , and resveratrol] D. Pyridoxine 10.5 mg E. Mg 90 mg F. Zinc 30 g details
 

Patient Age: 60
Patient Sex: M
Medical Problems: apigenin
fenugreek
hesperidin
resveratrol
saw palmetto, stinging nettle
tribulus
Medication History: Ticagrelor, ASA, metoprolol and atorvastatin. An Ace inhibitor will likely be started in next 24-48 hours.
Response: None of my references have any information about apigenin. (1-6) Fenugreek (1-5), or saw palmetto (1,3-5).

Saw palmetto may inhibit 3A4 but this was not documented when 3000 mg daily was taken for 8 weeks.(1) The concise dose of saw palmetto is indeterminable from the labelling but it would be no more than 280 mg per 4 capsules. Saw palmetto may have cardiovascular concerns. (1) NMCD states, “Occasional occurrences of hypertension, tachycardia, angina pectoris, arrhythmia, extra systole, angiopathy, myocardial infarction, and congestive heart failure have been noted in the clinical literature in association with oral saw palmetto use, although these reports have provided limited information to determine causality”.

Possibly resveratrol(1,4) and hesperidin(1) increase bleeding risk. Stinging nettle (1,4) and tribulus (1.4) may have hypotensive effects. None of the ingredients were considered harmful in general.(1-5)
References: 1. Natural Medicines - DI checker
2. Natural Medicines - monographs
3. Lexicomp
4. Micromedex
5. About Herbs
6. DerMarderosian A, McQueen C, eds. 2016. Review of Natural Products, The. St. Louis, MO. Facts and Comparisons® Publishing Group. ISSN 1089-5302. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?docAddress=DpksYdH8U_LRqcmPeRdKIQ%3d%3d. 2/16/2017 10:45:01 AM CST (UTC -06:00).

Feb. 21, 2017Is there any evidence for lysine to prevent HSV-2? (We know there is some for HSV-1). details
 

Response: There is some research suggesting lysine may prevent recurrent HSV infection(3,4,13,14) and that it appears to be dose-dependent.(4,13,14) Generally, HSV-1 causes orofacial lesions and HSV-2 causes genital lesions; that said, HSV-1 can less commonly be the pathogen.(11) The only trial that included patients with genital herpes is not available for review.(3) The abstract does not report how many of the patients had genital HSV, if the strains were typed, and of those with gential HSV, how many experienced positive results.(3) Another study that included patients with genital herpes was a survey inquiring about subjective improvement of episodes following lysine supplmentation. All of the limitations of the former trial apply as well as methodological limitations of a survey.(17)
The proposed mechanism of lysine is that it acts as an antagonist of arginine, which is required for herpes simplex virus replication.(6,8,9) HSV-2 also relies on arginine for replication.(8) Considering the typical daily dietary intake of lysine is 6-10 g and the usual dose is 1000 mg PO TID, serious adverse effects are not expected.(4) Adverse effects that have been reported include abdominal pain and diarrhea with daily doses of 10 g; a more serious event is that of Fanconi's syndrome reported in one patient who took 3000 mg daily for 5 years.(4,18)
Therefore, while there is no clincial evidence lysine will be effective to prevent genital herpes, risks are low should the patient still want to try it.
References: 1. Beauman JG. Genital herpes: a review. Am Fam Physician. 2005 Oct 15;72(8):1527-34. Review. PMID: 16273819
2. Groves M. Genital herpes: a review. Am Fam Phys. 2016; 93(11):928-934.
3. Griffith RS, Walsh DE, Myrmel KH, Thompson RW, Behforooz A. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica. 1987;175:183–90.
4. http://www.medscape.com/viewarticle/406943_5
5. http://www.altmedrev.com/publications/12/2/169.pdf
6. Ara DerMarderosian, PhD, Cydney E. McQueen, PharmD, eds. 2016. Review of Natural Products, The. St. Louis, MO. Facts and Comparisons® Publishing Group. ISSN 1089-5302. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?docAddress=nFetqneof3zaErDeI209Jg%3d%3d. 2/22/2017 8:40:10 AM CST (UTC -06:00).
7. Sen P, Barton SE. Genital herpes and its management. BMJ.2007;334(7602):1048-1052. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871807/
8. Development and evaluation of a host-targeted antiviral that abrogates herpes simplex virus replication through modulation of arginine-associated metabolic pathways.
Sanchez MD, Ochoa AC, Foster TP. Antiviral Res. 2016 Aug;132:13-25. doi: 10.1016/j.antiviral.2016.05.009. PMID: 27192555
9. Arginine inactivates human herpesvirus 2 and inhibits genital herpesvirus infection. Ikeda K, Yamasaki H, Minami S, Suzuki Y, Tsujimoto K, Sekino Y, Irie H, Arakawa T, Koyama AH. Int J Mol Med. 2012 Dec;30(6):1307-12. doi: 10.3892/ijmm.2012.1149. PMID: 23042569
10. National Center for Biotechnology Information. PubChem Compound Database; CID=5962, https://pubchem.ncbi.nlm.nih.gov/compound/5962 (accessed 22 Feb 2017).
11. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 114875, Genital herpes; [updated 2017 Feb 09, cited place cited date here]; [about 21 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=114875&site=dynamed-live&scope=site. Registration and login required.
12. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol. 1980; 60:85-7.
13. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg. 1984; 58:659-66.
14. McCune MA, Perry HO, Muller SA et al. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis. 1984; 34:366-73.
15. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infections. Arch Dermatol. 1984; 120:48-51.
16. Simon CA, Van Melle GD, Ramelet AA. Reply. (Failure of lysine in frequently recurrent herpes simplex infection.) Arch Dermatol. 1985; 121:167-8. Letter.
17. Walsh DE, Griffith RS, Behforooz A. Subjective response to lysine in the therapy of Herpes simplex. J Antimicrob Chemother 1983;12:489-496.
18. Natural Medicines

Feb. 21, 2017What is the prednisone equivalent of oral budesonide? Our patient is not responding to budesonide at a daily dose of 9 mg. Her MD has a sense of what prednisone dose is effective for her so wants to know the equivalent. details
 

Patient Sex: F
Response: Unlike other glucocorticoids, no well-established equivalent dose to prednisone is available for oral budesonide. However, in trials comparing oral prednisone to oral budesonide, 40 mg prednisone and 9 mg budesonide (1) or 10 mg (2,3) have resulted in similar remission rates of Crohn’s disease.
References: 1. National Advisory Committee on Immunization. Update on the use of herpes zoster vaccine. Public Health Agency of Canada. 2014 Jan. Available at http://publications.gc.ca/collections/collection_2014/aspc-phac/HP40-92-2014-eng.pdf . Accessed 2014 Mar 14.
2. Roth M, Gross V, Scholmerich J, Ueberschaer B, Ewe K. Treatment of active Crohn's disease with an oral slow-release budesonide formulation. Am J Gastroenterol 1993; 88: 968-9.
3. Rutgeerts P, Löfberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn’s disease. N Engl J Med 1994; 331: 842-5

Feb. 22, 2017Does "Jian Pai cream" (NPH - 80038015) interact with any of the patient's current medications? (ingredients include: sophorae glavescentis, borneol, gromwell root, phellodednon bark) details
 

Patient Age: 84
Patient Sex: F
Medical Problems: Thoracic aneurysm/hypertensive urgency
Psoriasis (uses herbal cream for treatment)
Medication History: Acetaminophen, atorvastatin, gravol, docusate, labetalol, ramipril, zopiclone
Response: I found that two ingredients were also referred to as lithospermum (arnebia guttata or gromwell) and camphor (borneolum or zhang hao or bing pian) and used those in my drug interaction analysis. (1,2, 3, 4, 5) I was unable to include sophora flavenscens (Ku Shen or sophora root) in my drug interaction analysis on Natural Medicines as I could not find another name for the drug.
The analysis of lithospermum, camphor and phellodendron showed drug interactions with acetaminophen, atorvastatin, and labetalol. Camphor is potentially hepatotoxic and should be used with caution with concomitant acetaminophen, atorvastatin, and labetalol as there may be an increase in liver enzymes and risk of developing liver damage. Phellodendron and atorvastatin should be used with caution as phellodendron might inhibit CYP3A4 enzymes, potentially increasing levels of atorvastatin and other CYP3A4 substrates. (6)
Patient is using topical products which likely decreases the chance of significant drug interactions however due to the lack of evidence of drug interactions with this product it should be used cautiously or discontinued.
References: 1. https://www.sacredlotus.com/go/chinese-herbs/substance/zi-cao-groomwell-root-arnebia-lithospermum
2. https://www.sacredlotus.com/go/chinese-herbs/substance/bing-pian-borneol
3. http://acupuncturetoday.com/herbcentral/borneol.php
4. http://08hachi.blogspot.ca/2011/08/dryobalanops-aromatica-gaertn.html
5. https://www.sacredlotus.com/go/chinese-herbs/substance/zhang-nao-camphor
6. Natural medicines database interaction checkler: https://naturalmedicines.therapeuticresearch.com/#

Feb. 24, 2017Patient is switching from Warfarin to Eliquis 5mg BID. The literature states to initiate apixaban when INR is less than 2.0 When stopping warfarin, what is a reasonable estimate of how long it would take for INR to decrease to less than 2? Patient's last INR was 2.0 on Feb 13th, and is due to repeat on Monday Feb 27th. My plan was to have patient go for INR on the 27th, and depending on what the result was, discontinue warfarin for 48 hours (2 doses) and then initiate apixaban. details
 

Patient Age: 80
Patient Sex: F
Medical Problems: 200 lbs
Atrial Fibrillation
Diabetes Type 2
Hypertension
Medication History: Warfarin 3mg EOD with 4mg, Starting Eliquis 5mg BID
Metformin 1000mg BID
Lisinopril HCTZ 20/25mg OD
Metoprolol 200mg BID
Forixga 10mg OD
Glyburide 5mg OD
Trazodone 50mg HS
Venlafaxine 225mg HS
Digoxin 0.0625mg OD
Rosuvastatin 20mg OD
Response: NOACs have a rapid onset of action and patients should wait until INR is 2.0 or lower before starting a NOAC. If INR testing isn’t readily available, it is reasonable to wait 2-3 days after last warfarin dose before starting a NOAC. (1,2) In the the ROCKET AF trial the highest INR prior to transition was 3.0 for starting rivaroxaban and the highest INR was 2.3 in trials for switching to dabigitran (RE-LY, RE-SONATE, and RE-MEDY). (3) These trials showed no indication that overlap of therapy was associated with increased bleeding risk. (3)
References: 1. Thrombosis Canada: New/Novel Oral Anticoagulants (NOACs): Comparison and Frequently-Asked Questions. Accessed Feb 28 2017. http://thrombosiscanada.ca/?page_id=18#
2. RxFiles
3. Schulman, S., & Crowther, M. A. (2012). How I treat with anticoagulants in 2012: new and old anticoagulants, and when and how to switch. Blood, 119(13), 3016-3023. Accessed February 27, 2017. https://doi.org/10.1182/blood-2011-10-378950.
4. Lexi-drugs

Feb. 24, 2017We have a patient who started Lantus 3 weeks ago and has had nasal congestion since. Is there any information available on that effect? Will it resolve on it's own? details
 

Medical Problems: no other medical problems disclosed
Medication History: Lantus insulin
Response: Sinusitis and rhinitis are relatively common adverse events associated with Lantus; sinusitis occuring in ~3-18% and rhinitis occuring in ~3-6% of patients. (1, 2, 4, 5). These side effects may go away with time as the product is being used. (4) Recommmend continuing on with Lantus as the side effects may become resolved or reduced over time. If the symptoms are moderately bothersome the patient could try a saline nasal spray or an intranasal corticosteroid. (3)
References: 1. SIDER- Lantus
2. Lexidrugs- Lantus
3. M. Varghese, M. C. Glaum and R. F. Lockey, Clinical & Experimental Allergy, 2010 (40) 381–384
4. https://www.drugs.com/sfx/lantus-side-effects.html#refs
5. Lantus product monograph (Sanofi-Aventis)

Feb. 27, 2017Can you use an oral DHEA as an alternative to topical DHEA 0.5% for the purpose of vaginal dryness? details
 

Patient Age: 45
Patient Sex: F
Medical Problems: hx breast cancer (currently in remission)
vasomotor symptoms + vaginal dryness (menopausal)
Mental health (depression + anxiety)
insomnia
osteoporosis
Medication History: gabapentin 900mg daily ( hot flashes)
sertraline 100mg qhs( depression + anxiety)
tamoxifen 20mg qam
topical DHEA 0.5% 1.3 mms daily (vaginal dryness)
Response: DHEA cream (applied vaginally or to the thigh) and intravaginal suppositories have shown to be effective in treating vaginal atrophy in post menopausal woman. (1) DHEA is the precursor of sex steroids and supposedly acts on local tissues to convert precursors into estrogens and androgens. (2)DHEA has been taken safely by mouth for 12-24 month, a DHEA 1-10% cream up to 12 months, and inside the vagina for 12 weeks. DHEA is possibly unsafe when used orally for long term at higher doses; long term use of 50 to 100 mg of DHEA daily can produce higher DHEA serum levels and potentially puts them at risk for cancer including breast cancer. (1)
It is reported that oral DHEA supplements may stimulate growth of mammary cancer cells in presence of low level estrogen. (3) This may be due to a DHEA metabolite directly affecting mammary cells, indirectly increasing estrogen levels, or through an increased concentration of free-insulin like growth factor that may stimulate oestrogen receptors. (3) Studies have reported a positive correlation between higher serum concentrations of DHEA and increased breast cancer risk in postmenopausal woman (but not premenopausal women). (3) Vaginal localized DHEA has minimal to none changes in serum steroids as patients have remained within normal post menopausal ranges. (4) It is not suggested to use vaginal estrogen therapy or vaginal DHEA in patients on aromatase inhibitors with breast cancer, however low dose use in breast cancer patients with a low risk of recurrence may be reasonable and should be determined by the patient’s oncologist. (4)
References: 1. Natural Medicine Database- DHEA
2. Sage Journals: treatment of vaginal atrophy- http://journals.sagepub.com/doi/full/10.2217/WHE.14.9
3. http://www.nature.com/ejcn/journal/v53/n10/abs/1600889a.html
4. UptoDate

Feb. 27, 2017When will the drug Dupilumab be available? It is used for "itchy, scratchy skin" (urticaria?) details
 

Response: Dupilumab does not have a notice of compliance yet. (1) Sanofi hopes to get FDA approval around the end of March 2017.
In two phase 3 trials it showed a reduction of 2 or more points from baseline and a score of 0 or 1 (clear or almost clear) in approx 37% of dupilumab compared to the 10% who received placebo in atopic dermatitis. The studies were over 16 weeks therefore longer term efficacy studies are required(2).
References: 1. Health Canada Notice of Compliance
2. http://www.nejm.org/doi/full/10.1056/NEJMoa1610020
3. http://www.pmlive.com/pharma_news/sanofi_eyes_march_approval_for_dupilumab_in_atopic_dermatitis_1144809

Feb. 27, 2017How long does it take for antihypertensives to have a full effect? Specifically amlodipine. Patient is on multiple blood pressure medications and we are wondering when we should try to increase their dose of amlodipine 5 mg po BID? details
 

Medical Problems: BP > 160/90 sometimes up to 200/90
Medication History: Hydrochlorthiazide 12.5 mg - increasing 25 mg (feb 28th)
Candesartan 32 mg
Metoprolol 50 mg po BID
Amlodipine 5 mg po BID
Response: Amlodipine steady state is usually reached within 7-8 days of consecutive daily dosing. (3 ) BP response should be evaluated 2 to 4 weeks after initiating or making changes in therapy. (2). Amlodipine will have significant reductions in BP at 24-48 hours after first dose. (1)
References: 1. http://accesspharmacy.mhmedical.com/drugs.aspx?GbosID=133634#monoNumber=133634§ionID=153409904&tab=tab0
2. Depiro Pharmacotherapy textbook - hypertension
3. Drug product database- amlodipine accel pharma

Feb. 28, 2017An MD has prescribed Albendazole 400mg OD x 1 wk for what they think is cutaneous larva migrans (the patient has recently returned from a trip to Jamaica). This medication is only available through SAP so is there some other medication that can be used? details
 

Patient Sex: F
Medical Problems: ?cutaneous larva migrans (CLM)
Medication History: no info available
Response: The drugs of choice are Ivermectin and albendazole (ivermectin preferred). (1,2,3) Both are only available through SAP. Dose of ivermectin: 12mg or 200mcg/kg po x 1 dose. (1,2,3) No other available treatments are recommended. In fact, there is a Canadian article which addressed the fact that CLM "treatment in Canada is only available through the Special Access Program (SAP) of Health Canada, thus, many patients are prescribed ineffective courses of non-targeted therapy" and the importance of using the first line treatments: ivermectin and albendazole. (2)
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 115661, Cutaneous larva migrans; [updated 2015 Nov 01, cited 2017 Feb 28]; Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=115661&site=dynamed-live&scope=site. Registration and login required.
2. Kincaid L, Klowak M, Klowak S, Boggild AK. Management of imported cutaneous larva migrans: A case series and mini-review. Travel Med Infect Dis. 2015 Sep-Oct;13(5):382-7 PMID: 26243366
3. Helmut Albrecht, M.D., Carlos Franco-Paredes, M.D., MPH. Cutaneous Larva Migrans. Antimicrobe: Infectious Disease & Antimicrobial Agents. http://www.antimicrobe.org/b08.asp#t7

Mar. 1, 2017Ondansetron 4-8mg BID is given to chemotherapy cancer patients for a couple days following treatment to prevent nausea. There is often a drug interaction showing up if the patient is on other agents that prolong the QTc interval. Is this a concern when the patient is on a low dose on Ondansetron for a couple days? All I have found is it would be an issue with IV Ondansetron. details
 

Response: Ondansetron prolongs QT interval in a dose dependent manner, especially in doses greater than 32 mg IV. (1, 3) Arrythmias, torsades de pointes, atrial fibrillation and other cardiac dysfunction have been reported during post marketing use of ondansetron IV injection although causation has not been confirmed. (4) In a RCT cross-over trial with healthy patients, researchers found a maximum mean difference in QTc interval of 19.5 milliseconds with a single dose 32 mg IV ondansetron which was significantly higher than the mean QTc max of 5.6 msec with 8 mg IV ondansetron (doses were infused over 15 minutes). (4). Risk of dose dependent QT prolongation is expected to be greater with faster and larger IV infusions of ondansetron. (6) The initial IV dose of ondansetron in patients > 75 years old must not exceed 8 mg and patients < 75 years old must not exceed 16 mg IV. (6) Infusions should be no less than 15 minutes. (6) Oral ondansetron is approximately 85% bioavailable in cancer patients and approximately 50-70% bioavailable non cancer patients due to first pass metabolism. (10) There however have been no recommended changes for oral dosing. (6)

Be aware of common QT prolongation drugs including quinolones, macrolides, and antipsychotics. (8) If patient has multiple risk factors (female, elderly, electrolyte disturbances, cardiac dysfunction etc.) for QT prolongation or is on combination of medications known to cause QT prolongation a baseline ECG may be warranted. (1) A good website specifically for QT prolongation and TdP risk with medications commonly prescribed for cancer patients is Credible Meds for Healthcare Professionals OncoSupport Drug List. (9) In conclusion, it seems ondansetron high dose IV has the most risk for QT prolongation. Suspect that occasional low dose oral ondansetron would have less/minimal significant QT prolongation (Rx files threshold < 10 msec) however patient factors and medications may contribute to increased QT prolongation and patient should be assessed appropriately. (1)
References: 1. Downey, S. Jensen, B. Reiger, L.QT prolongation and torsades de pointes: drugs and sudden death. 10th ed. Saskatoon, SK: Saskatoon Health Region. [updated 10 Oct 2014; accessed 02 March 2017]. Available from: http://www.RxFiles.ca
2. Credible meds
3. SIDER
4. Micromedex
5.FDA https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm310219.htm
6. Health Canada http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2014/39943a-eng.php?_ga=1.67850004.406906479.1452788418

Mar. 1, 2017Our patient is on a fentanyl 25 mcg patch. We tried to reduce her to the 12 mcg patch but she is having intolerable "crawling skin feeling". She experiences sweats and shakes and says that she can tolerate that but the skin crawling feeling is not tolerable. Are there any options for this? We were considering adding on clonidine for withdrawal but the patient is concerned with this as she tends to have low BP. She has not tried anything else in the meantime. details
 

Medication History: Taking buproprion x 150mg OD
Temazepam 30 mg HS
Response: Clonidine may reduce physical symptoms of withdrawal. To ensure it will be tolerated a test dose of 0.1 mg can be given with HR and BP being checked 1 hr after the dose administration. If BP < 90/60, postural hypotension or HR < 60 it shouldn’t be further prescribed. (3)
Methadone and buprenorphine have shown to be superior over clonidine in treatment of supervised withdrawal as two meta-analysis showed patients were more likely to complete treatment and reduce withdrawal symptoms. (1) Baclofen has also been used in opioid withdrawal. (2)
References: 1. Uptodate
2. Dynamed: opioid abuse or dependence
3. Rx files- slow opioid taper
4.RxTx: drug withdrawal syndromes

Mar. 1, 2017Patient is on Dexilant and finding it expensive. What is a PPI that is as effective and less expensive? details
 

Medical Problems: Likely dyspepsia (patient said there is no actual diagnosis)
Response: All of the PPIs are of equal equivalence(1); none are superior so cost and formulation are the major decision factors. Patient has no third party insurance and is covered by the Saskatchewan formulary (SDPEBB). The SDPEBB has recently implemented a MAC policy for PPIs: pantoprazole and rabeprazole are covered under this policy.(2) All other PPIs will be more expensive by virtue of their higher cost/dose and that the SDPEBB will only cover up to the cost of rabeprazole or pantoprazole.(2) Suggested to switch to pantoprazole or rabeprazole.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-GI-EvidencePearls.pdf
2. http://formulary.drugplan.ehealthsask.ca/News.aspx

Mar. 1, 2017I am giving a presentation on pre-exposure prophylaxis (PrEP). How much does a month of PrEP cost? Does a GP prescribe it? details
 

Response: Truvada is currently the only drug indicated for PrEP in Canada.(5) The cost of this drug is ~$850/30 day supply. The drug is not covered on the Saskatchewan formulary for this indication so all Saskatchewan formulary patients would pay out of pocket. Some third party insurers are covering on a case-by-case basis but maximums and deductibles may result in incomplete coverage.(6) It appears NIHB patients are covered for this drug as there are no restrictions to its indication.
The GP can prescribe. However, prescription of PrEP should include a comprehensive prevention strategy as well as routine follow-up (every 3 months) to monitor HIV status, adverse effects, and re-inforce prevention strategy.(2,5) If a GP is not comfortable with this, they can refer patients to Infectious Disease physicians (this is the case in Saskatoon.)(6)
References: 1. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
2. RxTx - Truvada
3. NIHB
4. PharmaClik
5. http://www.catie.ca/en/fact-sheets/prevention/pre-exposure-prophylaxis-prep
6. Phone communication with Pharmacist, Positive Living Saskatoon, 655-0688

Mar. 1, 2017What is the long term safety of tranexamic acid? Patient had fibroids removed and has had 5 courses of it to date. details
 

Medical Problems: fibroids removed
Medication History: Tranexamic Acid
Response: Information is available from one observational study looking at long-term effects of tranexamic acid being used cyclically for menorrhagia. This study included 723 women who were followed for 27 cycles of 1.3 g TID for up to 5 days per cycle. The discontinuation rate was 69.5%, the reason being adverse in 17.8%.
Specific adverse events reported:
- severe blurred vision occurred in one patient which resulted in discontinuation from the study
- nausea was one of the most frequently reported treatment-emergent gastrointestinal adverse events occurring in 14.4% (104/723) of patients
- the mean decrease in platelet count from baseline to study termination was -13,233 (from 298,791 to 282,689)
- a case of severe allergic reaction (dyspnea, throat tightening, and facial flushing) that required emergency medical treatment was reported in a patient on her fourth treatment cycle
- arthralgia occurred in 14.5% (105/723) of patients
- back pain occurred in 31.4% (227/723) of patients
- migraine occurred in 10.8% (78/723) of patients (1)
References: 1. DrugDex
2. Ophthalmological examination of patients in long-term treatment with tranexamic acid. Theil PL. Acta Ophthalmol (Copenh). 1981 Apr;59(2):237-41. PMID: 7257742

Mar. 1, 2017UTIs are a common SE of Invokana. How are they usually managed? Patient was put on chronic MacroBID daily. details
 

Medical Problems: diabetes (T2DM)
Medication History: Invokana
MacroBID
Response: Patients on long-term treatment of MacroBID for 6 months or longer are at increase risk of developing chronic pulmonary reactions, including diffuse intersistial pneumonitits, pulmonary fibrosis or fatalities. Pulmonary fibrosis has most frequently occurred in post menopausal woman and most cases have been reversible following discontinuation of MacroBID and beginning steroid therapy. (1) The most serious chronic effects involve the pulmonary and hematologic systems, as well as various peripheral neuropathies. (2) Neuropathy has occurred in elderly, renal dysfunction or chronic use of macrobid patients. (2)
References: 1. Micromedex- Macrobid
2. Toxnet - Macrobid

Mar. 1, 2017A patient undergoes PD dialysis QID. Cephalexin 500 mg QID has been prescribed. The dose adjustment for hemodialysis is 250 mg every 12-24 hrs with supplemental dose 250 post dialysis. Does PD dialysis remove as much as hemodialysis? Is this dose too much? details
 

Response: The manufacturer does not provide dosing adjustment for cephalexin however some clinicians follow the guidelines 250 to 500 mg every 12 to 24 hrs. (1) Patients with PD should receive the same dose as those with renal failure. (2)
References: 1. Lexidrugs

Mar. 2, 2017We have an ALS patient using Atropine Drops. His sister is asking if they can harden the saliva. Apparently he is coughing a lot now - a choking type of cough and they feel it is because his secretions are too thick. details
 

Patient Sex: M
Medical Problems: ALS
Medication History: Scopolamine patch
Atropine Drops SL qid
Response: ALS patients do have problems with thickening secretions for 3 reasons:
1) drying of secretions with medications such as the Atropine and scopolamine
2) low airflow as a person’s breathing capacity declines
3) loss of diaphragm muscle strength which diminishes the ability to cough. (1)
Guaifenesin is a recommended treatment: 400mg po every four hours. (1,2) Other medications that can help break up thick secretions are nebulized salbutamol, Combivent or Mucomyst used up to QID on a regular basis. (2)
References: 1. Secretion Management in ALS @ http://www.alsphiladelphia.org/document.doc?id=1983&frsid=5848
2. Catherine Lomen-Hoerth. Amyotrophic Lateral Sclerosis from Bench to Bedside Semin Neurol. 2008;28(2):205-211. @ http://www.medscape.com/viewarticle/572273_6

Mar. 2, 2017Is there any information about an association between PPI use and glaucoma? details
 

Patient Age: 57
Patient Sex: F
Medical Problems: Glaucoma diagnosed Oct 16
Medication History: Pantoprazole 40 mg daily started in Feb 16
Response: Drugs which are known to cause or exacerbate glaucoma include corticosteroids, antimuscarinic drugs (antihistamines, antidepressants, antispasmodics), and topiramate. (2). Pantoprazole is known to cause visual disturbance in less than 1% of patients. (1) In post marketing surveillance there have been reports of ischemic optic neuropathy and blurred vision. In another study treating patients with Zollinger-Ellison syndrome or hypersecretory conditions, 4 of 34 patients experiencd visual disturbances including blurry vision and eye floaters, appearing or worsening during pantoprazole use. (1) Spontaneous and slow resolution over six months was reported. (1) I did not find anything specifically that pantoprazole can contribute to or cause glaucoma however it does appear to cause eye disturbances in very few patients.
References: 1. Micromedex- Pantoprazole
2. Rxtx - glaucoma
3. Rxfiles- glaucoma

Mar. 2, 2017I work at the LTC facility in Duck Lake. I'm sure that Versed can be used SC in palliative patients, but our local pharmacy says it can't. What can you tell me? details
 

Response: Subcutaneous administration of Versed is an off-label use, however, it is often used this way in palliative care. (1,2,3) I'm including a link to a SHR document listing meds that can be used SC in palliative care. (1) If you need more information, please let us know.
References: 1. https://www.saskatoonhealthregion.ca/about/NursingManual/1074.pdf
2. Masman AD1,2,3, van Dijk M4,5, Tibboel D4,5, Baar FP4,6, Mathôt RA. Medication use during end-of-life care in a palliative care centre. Int J Clin Pharm. 2015 Oct;37(5):767-75.
3. Nathan Cherny. Palliative sedation. In: UpToDate, Arnold, RM (Ed),UpToDate, Waltham, MA. (Accessed on March 2, 2017.)UpToDate, Waltham, MA. (Accessed on November 25, 2013.)

Mar. 3, 2017Can Forxiga be given with insulin - in this case - Lantus and Humalog? details
 

Medical Problems: T2DM
Medication History: Lantus
Humalog
Response: Yes, if blood glucose is not well-controlled with the insulin combination. The dosage of the insulins should be decreased on initiation of the Forxiga because of the possibility of hypoglycemia (1,2) and adjusted as needed. (1,2)
References: 1. David K McCulloch. Management of persistent hyperglycemia in type 2 diabetes mellitus in UpToDate
2. Lexicomp interactions

Mar. 3, 2017We have received a prescription for Demerol 50mg 1-2 tabs qid prn. The patient is 72 years old. Is this appropriate? Is dosing too high? details
 

Patient Age: 72
Patient Sex: F
Medical Problems: Not known
Medication History: Not known
Response: Demerol should not be used for the treatment of acute pain unless other opioids are contraindicated or unavailable, especially if pain is expected to last > 3 hours. It's metabolite,- normeperidine, is neurotoxic and its accumulation can cause seizures or other CNS side effects such as tremors and hallucinations. Due to slower rate of metabolism in elderly and hepatic or renal impairment, use is not recommended in this population. (1,2)
The dosage seems fine. 50 to 150 mg every 3 to 4 hours as needed is recommended. (3)
References: 1. RxTx [Internet}. Ottawa (ON): Canadian Pharmacists Association; 2017. Bailey, B. Acute Pain; [updated August 2016; cited 03 March 2017]. Available from:https://www.e-therapeutics.ca/.
2. Mariano ER. Management of acute perioperative pain. In: UpToDate, Fishman S (Ed), UpToDate, Waltham, MA. (Accessed on March 3, 2017.)
3. Lexicomp Online

Mar. 6, 2017Is there any new information on the benefits of Lodalis? We are seeing more prescriptions for it. Any real evidence? I have someone with previous MI with stenting who is currently on ezetimibe only and cannot tolerate statins. Please reply to all details
 

Medication History: ezetimibe
Response: Lodalis (colesevelam) is a bile acid sequestrant used to lower cholesterol. It is indicated for use in those who cannot tolerate a statin or in addition to regular/reduced dosed statins. It works by preventing reabsorption of bile acids. Once bile acids are depleted, the hepatic enzyme cholesterol hydroxylase is increased which further converts cholesterol to bile acids. This in turn increases demand for cholesterol in liver and increases clearance of LDL from the blood. (2)

Lodalis is more potent than other bile acid resins (so smaller doses are appropriate), has fewer GI effects, and less influence on absorption of other drugs. (2) Some commonly reported side effects include constipation, dyspepsia, and nausea. (2) Lodalis will lower total cholesterol about 7-10%, LDL 15-18% and increase HDL about 3%. (2) It can increase triglycerides about 10% so it should be avoided in patients whom TG > 3.4 mmol/L. (2) It may reduce the absorption of ezetimibe. Therefore ezetimibe should be given two hours before or 4 hours after Lodalis. (3) I did not find evidence for Lodalis and associated CV risk reduction unlike statins.
References: 1. DynamedColesevelam
2. Pharmacists letter PL Detail-Document, New Drug: Lodalis (Colesevelam). Pharmacist’s Letter/Prescriber’s Letter. May 2012.
3. Lexi-drugs Colesevelam
4. Uptodate lipid lowering with drugs other than statins and fibrates

Mar. 6, 2017A patient was prescribed Metoclopramide for gastroparesis BEFORE starting Ralivia and Wellbutrin. She is wondering if she can start her metoclopramide again as her symptoms have returned. I'm getting mixed results on the severity of the interaction between Ralivia(tramadol) and metoclopramide. What is the mechanism behind this interaction? details
 

Patient Age: 45
Patient Sex: F
Medical Problems: Gastroparesis
Pain
Medication History: Cortef
Wellbutrin
Ralivia 100-200 mg OD
Metoclopramide
Response: Tramadol and metoclopramide may have drug interactions varying from increased sedation to increased seizures and serotonin syndrome. (2, 5) The risk of serotonin syndrome is potentially due to tramadol’s active metabolites binding to μ-opiate receptors in the CNS and inhibition of reuptake of norepinephrine and serotonin. (1)
High doses of metoclopramide block dopamine and serotonin receptors in the CNS and it is not recommended in addition to drugs with potential for extrapyramidal side effects due to increased seizure risk. (2)
Additionally, tramadol (CYP2D6 substrate) concentrations may be increased when given with CYP2D6 inhibitors such as bupropion. Tramadol’s opioid activity is due to conversion of metabolite whereas the parent compound has serotonergic activity. Therefore, reduced tramadol metabolism may further increase serotonergic activity with decreased opioid effect. (2, 4,7)
Overall, patient preference and risks vs benefits should be considered before restarting metoclopramide.
References: 1. Lexi-drugs tramadol
2. stockleys drug interaction checker
3. Lexi interaction checker
4. Lexi-drugs buproprion
5. Micromedex- tramadol and bupropion
6. Lexidrugs metoclopramide
7. RxTx- opioids

Mar. 6, 2017A patient is on a second round H. pylori treatment (the doctor wants to do second round for insurance of efficacy). Patient could not do original Hp-PAC. Is Pepto Bismol (bismuth subsalicylate) compatible with Pradaxa therapy? It was presumed the stomach bleed was caused by H. pylori so a blood test was redone and found to be positive. Pepto was not taken during the first course of therapy (thought it was only used for as needed therapy). Are there other options for treating H pylori in penicillin allergic patients? What is the Pepto there for? details
 

Medical Problems: Pencillin allergy
Medication History: Prevacid, bismuth subsalicylate, tetracycline, metronidazole
Pepto Bismol (bismuth subsalicylate) - 2 tabs QID for 14 days
Pradaxa 150 BID- second month filled today (was on warfarin for prevention of clots and then got a clot)
Response: No major drug interaction between Pepto Bismol and dabigatran. Each of these agents possess the potential to cause bleeding. Their combined use would seem to increase that potential. Recommended monitoring for increased signs of bleeding.
Increase monitoring diligence for signs and symptoms of bleeding if these agents are used concomitantly. (1, 2)
First line therapy for H pylori infections in penicillin allergic patients includes: Pepto Bismol, PPI, metronidazole and tetracycline. (3) An alternative therapy in pencillin allergic patients includes pantoprazole + clarithromycin + metronidazole. (3) Bismuth subsalicylate may exhibit antisecretory, antimicrobial, and anti-inflammatory effect. (5) Serology cannot be used to determine cure from infections (antibodies still detectable 6-12 months after eradication). (4)
References: 1. Lexidrug interaction checker
2. Stockleys drug interaction checker
3. Bugs and Drugs
4. Rxfiles h pylori testing and eradication
5. Lexidrugs- bismuth subsalicyclate

Mar. 6, 2017I have a 2 month old who vomits after every feeding. Is ranitidine the DOC? details
 

Patient Age: 0
Patient Sex: M
Medical Problems: 2 month old vomits after feeding
Response: Acid suppressing medications have a limited role in the treatment of infants with regurgitation. They are not valuable in treating children less than one year of age with uncomplicated GER ("happy spitters").
When pharmacotherapy is chosen as a treatment, or for a limited trial, a PPI is generally preferred over histamine type 2 receptor antagonists (H2RA). (1)
Gastroesophageal reflux: Limited data available: Corrected age <44 weeks: Oral: 2 mg/kg/dose every 8 hours (2)
References: 1)UTD - Gastroesophageal reflux in infants
2)Lexicomp - (Birch, 2009; Sutphen, 1989, Wheatley, 2012)

Mar. 6, 2017A 15 year old male (67 kg) with severe nodular acne (non responsive) was initiated on Accutane. He was tolerating 20 mg BID for 1 month well and then was increased 30 mg BID (1 month). Since the increase he's experienced a severe skin reaction (arms red, chapped breaking down, from wrist down, bilateral)- no other rashes on his arms. Front of neck is diffusely bright red, sharp demarcated line on the front (not extending to the back of the neck) - essentially where cold air come into contact with skin. The rash appeared about a week into his new dose. Skin is bright red and there is some dryness and chapping/chafing. He has been putting sunscreen on those areas. Is it safe to reduce to the dose of his accutane or should I discontinue it? details
 

Patient Age: 15
Patient Sex: M
Medication History: concerta
Response: Post marketing reports of severe skin reactions associated with Accutane, like Stevens-Johnson syndrome, toxic epidermal necrolysis, and erthema have been reported. A Roche global safety database (as of 2009) reported 66 incidences of severe skin reactions in adults and children worldwide, however there are approximately 16 million medication users. (2) Stevens-Johnson is generally associated with a fever, painful rash with lesions or vesicles and bullae, and can influence oral, ocular, and genital mucosa regions. (1) I agree the rash you described sounds like a photosensitivity as the redness is localized to exposed skin whereas more severe reactions tend to occur on various parts of the body and the rash is only presenting as redness. To manage the photosensitivity you can trial a decreased dose of Accutane or apply hydrocortisone cream to a small area to see if it helps reduce the redness and itchiness. (4)
References: 1. Uptodate
2. Health Canada- http://www.healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2010/14064a-eng.php
3. Micromedex- isotretinoin
4. http://emedicine.medscape.com/article/1049648-treatment

Mar. 7, 2017A patient is just starting Invega Sustenna and his mother would like to know in advance how one discontinues it. (There have been some bad experiences.) details
 

Response: Potential consequences of abrupt discontinuation (or large dose reduction) of an antipsychotic include discontinuation syndrome (flu-like), psychosis, and movement disorders.(1) However, because plasma concentrations of depot antipsychotics gradually decline, there is less concern of discontinuation syndrome and movement.(1) Certainly return of underyling condition is still a concern if not replaced by another antipsychotic.
References: 1. Clinical Handbook of Psychotropic Drugs, 20th Ed, pg 110

Mar. 7, 2017Does amlodipine interact with grapefruit juice? I've always told patients it did but now I'm looking on Lexicomp, Pharmacists Letter and eCPS and I am not finding any information. details
 

Response: There are some interactions with grapefruit juice and calcium channel blockers however none were recognized with amlodipine. (1,3,4) The sensitivity of the reaction with grapefruit juice may be related to the calcium channel blocker bioavailability. (1) Amlodipine has high bioavailability and is minimally affected by grapefruit juice whereas lower bioavailable CCBs such as felodipine are significantly affected by grapefruit juice. (1) The influence of grapefruit juice on bioavailablity of amlodipine seems to be neligible and not clinically significant. (1)
References: 1. Stockleys drug interaction checker
2. Pharmacists letter
3. Micromedex
4. Food and Drug interactions book

Mar. 7, 2017A patient is allergic to fentanyl patch (redness / welts on patch site). They have tried hydroxyzine and rotating patch sites. Are steroid creams or other dosage forms (e.g. Flovent spray) a possibility? details
 

Response: Topical steroids may be used in treating mild-moderate contact dermatitis.(1) Systemic steroids also provide relief within 12-24 hrs and are used if severe or widespread contact dermatitis occurs.(1) Trying another brand may be beneficial for the patient as the different brands have different adhesives. If skin irritation occurs with fentanyl patches, steroidal sprays have been used; wait 1 minute after spraying before applying the new patch.(2) There is minimal evidence for the steroid spray with allergic dermatitis and the sprays can be rather expensive if the patient has no coverage. However they can be used as a last resort.
References: 1. Dynamed
2. Rxfiles- opioid analgesics

Mar. 7, 2017Are there any drug interactions with azithromycin and this patient's medications? details
 

Medication History: Alprazolam
Cyclobenzaprine
Ranitidine
Response: No interactions identified (2).
References: 1. Lexi-drug interaction checker
2. Stockleys drug interaction checker

Mar. 7, 2017Could Invokana lead to elevated oxalates in the urine? Is there a list of medications causing elevated oxalates in the urine or information on what causes elevated oxalates? details
 

Response: It appears as if there are three conditions that can cause high oxalate content in urine or hyperoxaluria; an inherited genetic disorder, eating too many oxalate rich foods, and/or intestinal diseases that increase absorption of dietary oxalates such as gastric bypass, Crohn’s disease, short bowel syndrome or other malabsorption issues. With a genetic disorder the liver doesn’t create or produce enough enzyme to prevent over-production of oxalate (likely not influenced greatly by diet). In disorders with excess absorption via diet or intestinal disorder it may be more important to reduce oxalate content in diet. (3) Foods known to be high in oxalate content include rhubarb, spinach, potatoes, legumes and nuts (1) Patient may also require a low-fat diet. (1) It also appears that high dose vitamin C may increase absorption of oxalate. (1) If there is excess absorption of oxalate then calcium carbonate or cholestyramine may be used to reduce absorption. (1) Patient should undergo testing to determine if they have a genetic disorder or excessive absorption causing high oxalate content in the urine. (2) I did not find information regarding Invokana increasing urine oxalate levels.

An association of oxalates and vulval pain was found involving a woman with vulvodynia. She presented with high levels of oxalate in her urine. Her symptoms resolved and oxalate levels declined after starting a low-oxalate diet and calcium citrate to remove oxalate from the body. In the US, a low oxalate diet is widely used for treatment of vulvodynia. (4)
References: 1. Up to date- prevention of recurrent calcium stones in adults
2. Uptodate – primary hyperoxaluria
3. Ohf.org – oxalosis and hyperoxaluria foundation
4. Vulval pain society- http://www.vulvalpainsociety.org/vps/index.php/treatments/the-low-oxalate-diet

Mar. 10, 2017How should I manage the Dostinex drug shortage? What are some alternative therapies? details
 

Response: Shortage is estmated to be resolved April 6th. Please see medSask Drug Shortages cabergoline PDF on how to manage cabergoline shortages.
References: 1. http://www.drugshortages.ca/searchresult.asp
2, http://www.medsask.usask.ca/documents/drug-shortages/Cabergoline.pdf
3. Pharmaclic - Cabergoline

Mar. 10, 2017A patient has been on amantadine 100 mg TID with food. It is shorted. What can we do? details
 

Patient Age: 78
Patient Sex: M
Medication History: Levodopa/carbidopa CR and regular
Trihexyphenidyl 2 mg TID
Quetiapine 12.5 mg TID
Response: Referred to Amantadine shortages document.(1)
References: 1. http://medsask.usask.ca/documents/drug-shortages/Amantadine%20Hydrochloride.pdf

Mar. 10, 2017Do I need to document the sale of Olex like I do for Tylenol #1? details
 

Response: Schedule II means a pharmacist needs to be involved in discussion with the patient.(1) There is no legislation for omeprazole compelling pharmacies to document sales, whereas this is the case with Tylenol #1.(2)
References: 1. http://scp.in1touch.org/uploaded/web/refmanual/Regulatory_Bylaws_Current.pdf
2. http://scp.in1touch.org/uploaded/web/refmanual/Exempted_Codeine_Products_20140610.pdf

Mar. 10, 2017How frequent/severe is cross-sensitivity reaction with nortriptyline and carbamazepine (prescribed yesterday for TMJ)? The patient had a rash with nortriptyline and there is very little/weak information about the cross sensitivity with CBZ. He is NOT of Asian descent but is of Lebanese heritage (is a landed immigrant). Not sure if the cross sensitivity is a factor in developing the fatal skin reaction. Can you weigh in? details
 

Patient Age: 54
Patient Sex: M
Medical Problems: Chronic Pain
TMJ
HTN
Migraine (unsure if with/without aura)
Allergies: Nortriptyline : RASH Note: tolerating Amitriptyline
Medication History: Nabilone, Amitriptyline, Hydromorph contin, Botox injections (for migraines)
**Carbamazepine 100mg (chew) BID ** (new not dispensed)
Metoprolol
Response: It is true that TCAs and carbamazepine (CBZ) share similar structures. CBZ has been associated with serious skin reactions including Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).(3) Furthermore, there are five reported cases of patients who experienced a hypersensitivity reaction to a TCA after a prior reaction to CBZ.(2)
However, only if your patient’s reaction to nortriptyline involved more than rash (i.e. systemic effects such as chills, fever) or was severe would complete avoidance of CBZ be warranted. The fact your patient is tolerating amitriptyline is reassuring. I think it’s important the patient be educated to immediately report any dermatological reactions but there appears to be no reason to avoid CBZ altogether.
References: 1. Lexicomp Aromatic Anticonvulsant Allergy/Hypersensitivity (Drug Allergy and Idiosyncratic Reactions)
2. Seitz CS, Pfeuffer P, Raith P, et al. Anticonvulsant hypersensitivity syndrome: cross-reactivity with tricyclic antidepressant agents. Ann Allergy Asthma Immunol. 2006 Nov;97(5):698-702. PMID 17165282
3. DrugDex

Mar. 10, 2017How significant is the interaction between mycophenolate and PPI? Can they just monitor the levels and adjust the dose as needed? details
 

Medical Problems: indications unknown
Response: Proton pump inhibitors (PPIs) may decrease serum mycophenolate acid levels, depending on the product used.(1,2) Several studies have suggested significant reductions (17-37%) in the active metabolite, mycophenolic acid (MPA), when PPIs have been combined with mycophenolate mofetil (MMF).(2) However, other studies have shown no significant difference in MPA levels with MMF and PPI use.(2) The clinical significance and apparent interaction is unclear so caution is warranted with the combination.(2)
It appears as if the enteric coated mycophenolate sodium tablets (EC-MPS) are less sensitive to the PPI interaction and it may be an alternative to patients needing a PPI.(1,2) Most studies reported no significant change in MPA levels with enteric coated mycophenolate sodium and PPI.(2)
Those receiving higher doses of PPIs may be at increased risk of lower MPA levels.(2) Data suggests pantoprazole may not affect mycophenolate and one study suggested low dose rabeprazole didn’t affect mycophenolate concentrations.(1) Serum/plasma monitoring is not undertaken for MMF (3) so monitoring takes the form of observation of clinical response. If the MMF is being used post organ transplant, one may want to consider avoiding PPIs or using EC-MPS.
References: 1. Stockleys Drug Interactions
2. Lexicomp Drug Interaction Checker
3. eCPS

Mar. 10, 2017What schedule is Synvisc? details
 

Response: Synvisc (hyaluronic acid in concentrations of 5% or more) is Schedule II.(1,2) The hyaluronic acid products for which concentrations are available (Euflexxa, Durolane, Monovisc, Neovisc, Synvisc, Synvisc-One) are <5% (3-5) and, therefore, unscheduled.
References: 1. NAPRA National Drug Schedule
2. http://scp.in1touch.org/uploaded/web/refmanual/Administrative_Bylaws_CURRENT.pdf
3. RxTx
4. Lexicomp
5. http://www.durolane.com/img/document/DUROLANE_Science_of_the_single_injection.pdf

Mar. 10, 2017Patient has been treated for parasites in the intestine with Vermox, then Combantrin; both failed. MD has prescribed Humatin but the family can't afford it. Are there any other agents that could be used? details
 

Patient Age: 8
Patient Sex: M
Medical Problems: Intestinal parasite - dientamoeba fragilis, blastocytis hominis
Medication History: Tried Vermox and Combantrin
Response: Metronidazole 50 mg/kg/day PO divided TID x 10 days is the most suitable alternative.(1) It is effective for blastocystis hominis and is an alternative for dientamoeba fragilis.(1) The preferred treatments for dientamoeba fragilis are iodoquinol, which is no longer available(2) and paromomycin, which was prescribed but is not affordable.
References: 1. Bugs and Drugs app
2. DPD

Mar. 10, 2017A patient is currently on Butrans patches and is switching to medical marijuana? How do I go about this? details
 

Response: There is no equivalent dose of opioids and marijuana. Tapering of high dose opioid can be considered before starting marijuana as there may potentially be additional CNS depression with the combination. (4)
A taper may be considered to reduce withdrawal symptoms if receiving a higher dose buprenorphine patch, however withdrawal is generally mild and resolves in 2 weeks. (2) You may want to begin by reducing the patch every 10 days to the lowest dose tolerated. (2) Additionally, there is an estimated dose equivalency for the patch and other opioids on RxFiles Q and A: Butrans Patch for Weekly Application for converting opioids to Butrans patches which may be of some assistance.
Levels of the drug usually decline 50% after removal of the patch after approximately 12 hrs. (2) Administration of other opioids should be delayed at least 24 hrs after removal of patch. (2)
The initial usual dose of smoked marijuana is 65-195 mg. (5) The Health Canada website is a useful resource for further information about medical marijuana.(6) If the patient is in the process of seeking medical marijuana, do not begin the taper until it is approved because approval may take some time.
References: 1. Health Canada drug product database- buprenorphine
2. RxFiles: BuTrans Patch Buprenorphine Transdermal System (BTDS) for Weekly Application
3. http://www.helpmegetoffdrugs.com/taper#form
4. Pharmacists Letter- Medicinal Marijuana
5. Rxfiles: Cannabindoids
6. http://www.hc-sc.gc.ca/dhp-mps/marihuana/med/index-eng.php

Mar. 10, 2017Dose prednisone decrease ASA levels? Is this of concern for someone taking low-dose ASA? Should the ASA dose be increased? details
 

Response: Serum salicylate levels are reduced by steroids; however the main concern is following steroid withdrawal in those taking moderate to high doses of ASA.(1) The discontinuation of the steroid may result in increased ASA levels (has been associated with a 3 to 9 fold increase) and symptoms of toxicity.(2) As low-dose ASA is not expected to interact,(1) no dose adjustment is required.
References: 1. Stockleys Drug interactions
2. Lexidrugs interaction checker

Mar. 13, 2017A patient was prescribed Zofran orally dissolving tablet but the regular tablet was dispensed. What is the difference? It says they have the same bioavailability, but do the dissolving tablets work faster? details
 

Response: There is no difference in terms of bioavailability or onset of action between the two products.(1,2) The ODT tablets are placed on the tongue and swallowed after disintegration; as such, they are also absorbed orally.(3) The ODT tablets may be advantageous for those who have trouble swallowing tablets, or for those who are too nauseous to drink liquid/swallow a tablet or capsule.(3)
References: 1. Micromedex- Ondansetron
2. Lexidrugs - Ondansetron
3. Canadian Pharmacist's Letter 2013; 20(11):291130

Mar. 14, 2017What are the treatment options for eosinophilic esophagitis? A patient was prescribed an Advair MDI but told to swallow the treatment; would a nasal spray be better? Are allergy shots warranted? The patient's allergy specialist told her it would be beneficial but to research it herself. details
 

Medical Problems: eosinophillic esophagitis (EoE)
Medication History: Advair, PPI- using for esophagitis (but not effective)
PO prednisone in the past
Response: Treatment of eosinophilic esophagitis (EoE) consists of:
1. Acid Suppression with PPIs- PPIs may be beneficial for EoE by reducing acid production in patients with co-existent GERD or through other anti-inflammatory mechanisms. As the esophagus may be inflamed, PPIs will confer protection to potential acid exposure. Approximately 1/3 of patients have good results with PPI alone. In a randomized study patients received esomeprazole 40 mg for 8 weeks along with swallowed fluticasone; treated patients experienced significant improvement in symptoms of dysphagia regardless of GERD status.(1) These may not be appropriate if the patient is not finding any benefit from the PPI.
2.Topical glucocorticoids: Most patients receive swallowed fluticasone which is administered using an MDI without a spacer. The medication is sprayed into the mouth and swallowed; the patient should not eat or drink for 30 minutes after administration. Adults should use 500 mcg twice daily. If treatment is not beneficial, the dose may need to be increased or the patient can be switched to oral viscous budesonide (budesonide nebules mixed with sucralose [4]). Budesonide can also be administered using a nebulizer and having the patient swallow the accumulated liquid. Patients generally continue with treatment for 8 weeks and if relapse is an issue afterwards a maintenance dose or dietary changes may be considered. (1)
Desensitization with purified known allergen could be effective in controlling EoE. It may reduce the burden of allergy and risk of anaphylaxis however there is the possibility that the immunotherapy may trigger the EoE (as seen in mice). Further research is needed to determine safety and efficacy. (2)
Other potential therapies for EoE include systemic steroids (especially if patient has severe disease) and esophageal dilation. Esophageal dilation will relieve dysphagia but not improve the underlying inflammation. (1)
References: 1. Uptodate: Treatment of Eosinophilic Esophagitis
2.Doughtery T, Stephen S, Borum M, Doman D. Emerging Therapeutic Options for Eosinophilic Esophagitis. Gastroenterology & Hepatology Volume 10, Issue 2 [published Feb 2014, cited March 2017]. Available from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011375/
3. Uptodate: Management of benign esophageal strictures
4. Dohil R, Newbury R, Fox L, et al. Oral viscous budesonide is effective in children with eosinophilic esophagitis in a randomized, placebo-controlled trial. Gastroenterology. 2010 Aug;139(2):418-29.

Mar. 14, 2017Is there an interaction between carbamazepine and vaginal estrogen cream? If so, what is the mechanism? details
 

Medical Problems: indication for carbamazepine unknown
dry vaginal symptoms
Medication History: amitriptyline, Premarin vaginal cream
Response: Carbamazepine is an enzyme inducer that may increase estrogen metabolism, thereby reducing its effectiveness; however, this is not relevant for locally applied estrogen used for menopausal vaginits.(1) The combination has no effect on carbamazepine levels. (1,2)
References: 1. Stockleys Drug Interaction Checker
2. Lexicomp Drug Interaction Checker: carbamazepine, estrogens (conjugated, equine) systemic

Mar. 14, 2017What do you know about a short chain fatty acid enema for use in diversion colitis? details
 

Medical Problems: Not available
Medication History: Not available
Response: Diversion colitis is characterized by inflammation of the defunctionalized, bypassed colon following surgery. Most patients with diversion colitis are asymptomatic, but in a small proportion of patients, symptoms can significantly impact quality of life.(1) Diversion of the colon results in deficiency of short-chain fatty acids (SCFA) along with other nutrients. Bacterial metabolism results in SCFA synthesis. SCFA are absorbed by the lumen which then supplies fuel to mucosal cells, modulates fluids and electrolytes, enhances colonic motility and mucosal blood flow, and production of inflammatory cytokines. (1) SCFA enemas may be used as initial therapy for diversion colitis in those unable to undergo surgery. They may be used in IBD along with ASA and glucocorticoids. The enemas must be compounded and consist of sodium acetate (60 mmol), sodium propionate (30 mmol), and sodium n-butyrate (40 mmol) with additional sodium chloride (22 mmol). This yields a similar osmolality to plasma and pH is adjusted to 7.0 with sodium hydroxide. The enema is instilled twice daily for 6 weeks at a dose of 60 mls. Frequency may be reduced if improvement occurs. (1)
Sodium butryrate instillation has been shown to increase colonic mucin synthesis. (2) Further studies need to be done to determine the relationship between the mucous layer and diversion colitis. (2)
Results for SCFA enemas have been conflicting. In one randomized crossover trial of 10 patients with IBD and colectomy, SCFA enema use for 3 weeks was not shown to improve inflammation compared to placebo. However these patients had severe inflammation which may have been due to IBD. (1) Another study of 8 patients received SCFA and had significant increased proliferation of rectal mucosa compared to placebo. (3)
References: 1. Uptodate- Diversion Colitis
2. Kabir S, Kabir S, Richards R, Ahmed J, MacFie J. Pathophysiology, clinical presentation and management of diversion colitis: A review of current literature. International Journal of Surgery. [accessed March 14, 2017]. Available from: http://www.sciencedirect.com/science/article/pii/S1743919114008346
3. Mortensen F, Langkilde N, Jorgenson J, Hessov I. Short chain fatty acids stimulate mucosal cell proliferation in the closed human rectum after Hartmann’s procedure. International Journal of Colorectal Disease [published August 1999, accessed March 14, 2017]. Available from: http://link.springer.com/article/10.1007%2Fs003840050201

Mar. 14, 2017Is melatonin safe in breastfeeding? (The infant is 6 days old.) details
 

Response: There is minimal data for melatonin supplementation during breastfeeding and effects are relatively unknown.(1,2) Melatonin is naturally excreted in the breastmilk and infants have been safely given melatonin directly in doses higher than what would be expected from breastmilk.(2) That said, due to the limited information regarding the safety of melatonin supplmentation in breastmilk and that the infant is a neonate some recommend against its use.(1)
References: 1. Briggs in Pregnancy and Lactation
2. LactMed

Mar. 14, 2017My patient has an LDL 0.3, HDL 0.7, with a history of MI and is taking atorvastatin 40 mg once daily (recent increase from 20mg daily). Is there any evidence for statin therapy in low LDL patients? What is considered "too low"? Is there a benefit or is therapy still indicated if cholesterol levels are very low? details
 

Patient Age: 68
Patient Sex: M
Medical Problems: Previous MI
Heart failure
(No history of diabetes or hypertension)
Response: The common guidelines for statin therapy, such as that of the American College of Cardiology do not mention how to manage low LDL, but some articles have explored targeting lower LDLs to assess if there is a greater benefit with more aggressive treatment.
This patient would have been put on a statin following the heart attack, as this would be considered clinical atherosclerotic cardiovascular disease. (2) One of the four benefit groups according to the American College of Cardiology is patients with atherosclerotic disease; and it is recommended to put them on moderate to high intensity statin. (1) According to UpToDate, the existing data does not support any specific recommendations for patients that happen to present with an initial LDL baseline below 1.29 mmol/L, but they suggest that if therapy seems to be warranted, a low dose of statin is acceptable. (5)
Once statin therapy is initiated, however, there is not a lot of information on handling very low LDL levels; most studies look at “low” LDL (likely higher than 0.3mmol/L) or explore theoretical implications of very low LDL levels. According to the atherosclerotic Cardiovascular disease Primary Prevention Guidelines, it is not recommended to lower statin therapy in response to low LDL levels, saying “Expert opinion is that no LDL level is too low.” (11) With respect to there being benefit of continued therapy, DynaMed reported that all levels of cholesterol that are treated with statin therapy show a decrease in mortality and CV events, though the actual LDL numbers in that range were not disclosed. (2) Though there may not be mention of levels as low as 0.3mmol/L, some studies have mentioned that patients with conditions that create very low LDL levels (hypobetalipoproteinemia) with LDL below 1.86mmol/L have a lower risk of CV disease, as well as those on statin therapy with LDL below 1.7 mmol/L had a greater reduction in the occurrence of cardiovascular events. (10,12) The PROVE-IT trial found that a more aggressive target (<1.86mmol/L) showed a 16% relative risk reduction of primary composite endpoint that included all-cause mortality, MI, unstable angina requiring hospitalization, requiring a PCI or CABG, and stroke. (9) LDL <1.6 mmol/L was also shown to improve survival. (4)
As far as the risks associated with having a low LDL, statin patients with LDLs below 0.8mmol/L to 1.07mmol/L had side effect frequency comparable to those that had higher LDL levels on statin therapy, (6,12) with a slight increase in myopathy and risk of developing diabetes. (12) In studies that looked at the newer non-statin drug for lowering cholesterol (alirocumab), patients with LDL as low as 0.4mmol/L to 0.67mmol/L did not have a higher frequency of side effects, apart from a slight increase in risk of cataracts. (7) Low LDL is sometimes believed to be a risk for cognitive impairment. A systematic review of RCTs of statin therapy found no association between being treated with statins and cognitive decline; the LDL numbers of the study were not disclosed but it did include participants on higher intensity statin therapy. (3) Critical capacities of steroid hormone and bile acid production are preserved, and the cholesterol blood-brain barrier continues to protect cells of the central nervous system even at extremely low LDL-C levels. (13)
Bottom line is that therapy is likely still beneficial for secondary prevention in a post MI patient with low LDL levels, but it may be up to clinical judgement to determine the most appropriate dose to use for treatment.
References: 1. Micromedex
2. DynaMed
3. Ott B, Daiello L, Dahabreh I, Springate B, Bixby K, Murali M et al. Do Statins Impair Cognition? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Journal of General Internal Medicine. 2015;30(3):348-358.
4. Leeper N, Ardehali R, deGoma E, Heidenreich P. Statin Use in Patients With Extremely Low Low-Density Lipoprotein Levels Is Associated With Improved Survival. Circulation. 2007;116(6):613-618.
5. UpToDate
6. Wiviott S, Cannon C, Morrow D, Ray K, Pfeffer M, Braunwald E. Can Low-Density Lipoprotein Be Too Low? The Safety and Efficacy of Achieving Very Low Low-Density Lipoprotein With Intensive Statin Therapy. Journal of the American College of Cardiology. 2005;46(8):1411-1416.
7. Robinson J, Rosenson R, Farnier M, Chaudhari U, Sasiela W, Merlet L et al. Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab. Journal of the American College of Cardiology. 2017;69(5):471-482.
8. Healthline
9. PROVE-IT: Atorvastatin 80 mg reduces major CV events by 16% compared with pravastatin 40 mg in ACS patients
10. John C. LaRosa, MDa, , , Scott M. Grundy, MD, PhDb, John J.P. Kastelein, MDc, John B. Kostis, MDd, Heiner Greten, MDe. Treating to New Targets (TNT) Steering Committee and InvestigatorsSafety and Efficacy of Atorvastatin-Induced Very Low-Density Lipoprotein Cholesterol Levels in Patients With Coronary Heart Disease (a Post Hoc Analysis of the Treating to New Targets [TNT] Study). The American Journal of Cardiology. 2017;100(5):747–752.
11. Cohen A. © 1996 Kaiser Foundation Health Plan of Washington. All rights reserved. 1 Atherosclerotic Cardiovascular Disease (ASCVD) Primary Prevention Guideline [Internet]. Kaiser Permanente. 2016 [cited 14 March 2017]. Available from: https://www.ghc.org/static/pdf/public/guidelines/ascvd-primary.pdf
12. Kostis W. How Low an LDL-C Should We Go With Statin Therapy?. Current Atherosclerosis Reports. 2014;16(2).
13. Olsson A, Angelin B, Assmann G, Binder C, Björkhem I, Cedazo-Minguez A et al. Can LDL cholesterol be too low? Possible risks of extremely low levels. Journal of Internal Medicine. 2017.

Mar. 15, 2017With the discontinuation of dehydrated alcohol injection, we are looking for alternative treatments for methanol/ethylene glycol poisonings. We carry Fomepizole in one of our hospitals, but have not stocked it in all locations due to cost implications. - How quickly after ingestion does antidote therapy need to be instituted (ie: would we have time to transport a patient to another facility?) -What alternative therapies have good evidence? Is oral alcohol a good option- if so, looking for dosing parameters/protocols for both adult & pediatric patients details
 

Response: How quickly after ingestion does antidote therapy need to be instituted (ie: would we have time to transport a patient to another facility?)
- Other than the general recommendation of “begin treatment ASAP for better outcomes” (1,2), there was one study that specifically looked at the timing of providing the antidote and how it impacted outcomes (3). They found that delaying the antidote more than 6 hours increased rates of death OR prolonged renal insufficiency and associated morbidity significantly (composite end-point, odds ratio of 3.34). They do not conclude that giving the antidote within 6 hours is optimal (it could be within 1-2 hours, for example), but delaying more than 6 hours definitely leads to more harm. The optimal time to begin treatment is “as soon as possible.”

What alternative therapies have good evidence? Is oral alcohol a good option? If so, what are the dosing parameters/protocols for both adult & pediatric patients?
- Other than Fomepizole and intravenous ethanol, oral ethanol is the only other antidte; hemodialysis is the best treatment in the setting of severely poisoned treatments.(2)
o Note that oral dosing of ethanol is considered inferior to fomepizole or IV ethanol because (2):
-difficult to dose, and maintain appropriate levels -> necessitates frequent testing and infusion adjustments.
-higher likelihood of side effects
-lower cost, but increased monitoring makes it similar, or possibly worse, in terms of cost effectiveness compared to fomepizole (4). This is not definitive, however: a study from Europe (5) found using IV-ethanol was significantly more cost-effective than fomepizole in 96 poisonings. This World Health Organization suggests fomepizole is likely more cost-effective depending on regional costs of acquisition and staffing (6).
Oral ethanol dosing protocols suggested (for both pediatric and adult):
- Distilled spirits (40 to 50 percent vol/vol) intended for human consumption can be diluted to a 20 percent solution, and administered orally or via nasogastric tub, at a loading dose of 5 mL/kg of a 20 percent solution to raise ethanol serum concentrations by 1000 mg/L (22 mmol/L), and 0.5 mL/kg per hour for the initial maintenance dose.

O Another protocol (1) (basically the same, slightly lower dose):
- Oral ethanol may be used as a temporizing measure until intravenous ethanol or fomepizole can be obtained, but it is more difficult to achieve the desired stable ethanol concentration. The loading dose is 0.8 grams/kg (4 mL/kg of 20% {40 proof}) ethanol diluted in juice administered orally or via a nasogastric tube. Maintenance dose is 80 to 150 mg/kg/hour (of 20% {40 proof}) ethanol; 0.4 to 0.7 mL/kg/hour for a non-drinker; 0.8 mL/kg/hour for a chronic alcoholic). Concentrations greater than 30% (60 proof) ethanol should be diluted. For both modalities, blood ethanol levels must be monitored hourly and adjusted accordingly, and both require patient monitoring in an ICU setting.
References: 1. Micromedex, Toxdex: Treatment of ethylene glycol poisonings
2. UpToDate, treatment of ethylene glycol poisoning
3. https://www.ncbi.nlm.nih.gov/pubmed/24371252 - J Intensive Care Med. 2015 Jul;30(5):270-7. doi: 10.1177/0885066613516594. Epub 2013 Dec 26. Predictors of Death and Prolonged Renal Insufficiency in Ethylene Glycol Poisoning.
4. https://hero.epa.gov/hero/index.cfm/reference/details/reference_id/1230439
5. http://www.jccjournal.org/article/S0883-9441(17)30334-9/fulltext?rss=yes
6. http://www.who.int/selection_medicines/committees/expert/19/applications/Fomepizole_4_2_AC_Ad.pdf

Mar. 15, 2017Is Aclasta interchangeable with the generic? details
 

Medication History: Taro no stock, Aclasta
Teva - d/c
Dr. Reddy's - inventory
Response: Taro and Teva (5mg /100 ml) generics are available and approved for osteoporosis treatment but they aren't available right now. (1,2) There is a Dr. Reddy's zoledronic acid 5mg/100ml product available however is it only indicated for prevention of postmenopausal osteoporosis in women with osteopenia and Paget's disease.(1,2) More concentrated generics are available but they are indicated only for bone metastases . (1) We don't know why the Aclasta is the only version covered by EDS.
References: 1. eCPS
2. DPD
3. NOC database
4. http://www.gov.pe.ca/photos/original/PIDL.pdf
5. http://formulary.drugplan.ehealthsask.ca/PDFs/PREFACE_Updated_March_1_2017.pdf

Mar. 16, 2017Can melatonin be used for sleep in an individual who is 17 weeks pregnant? details
 

Patient Sex: F
Response: Melatonin: No Human Data—Animal Data Suggest Moderate Risk. (3) Melatonin doses very near the human dose based on body weight did adversely affect the development of the neuroendocrine reproductive axis in female rat fetuses. There is probably no relationship of this toxicity in pregnant humans consuming occasional low (≤10 mg) doses, but high doses or frequent use during gestation should be avoided. (3)
Schaefer has these recommendations:
▪ For sleep disorders requiring medication, sedating antihistamines, trazodone, amitriptyline, and, if necessary benzodiazepines or zolpidem are recommended
▪ Benzodiazepines are the drugs of choice for the brief treatment of acute symptoms and, in certain cases, sleep disturbances during pregnancy
▪ For sleep disorders requiring continuous medication, the antidepressants trazodone or amitriptyline are preferable.
(1)
References: References :
1. Schaefer, C., Wisner, K. Drugs During Pregnancy and Lactation Third Edition, 2.11, 293-339
2. UpToDate - Teratogenicity, pregnancy complications, and postnatal risks of antipsychotics, benzodiazepines, lithium, and electroconvulsive therapy. Accessed on-line 08Sep2016
3. Briggs, Gerald G.; Freeman, Roger K.; Yaffe, Sumner J., Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th Edition

Mar. 16, 2017At what rate do you suggest titrating Lipitor? Can you start at 10 mg and double the dose every 7 days to 80 mg? details
 

Medical Problems: Hx MI
high TG
high Framingham
Medication History: Statin-naïve, no interacting meds
Response: There is no indication to titrate statin doses.(1-4) Start with the required dose (in this case 80 mg); reduce if not tolerated.(4)
References: 1. http://www.cfp.ca/content/61/10/857.full
2. eCPS - Lipitor
3. RxTx - Post-myocardial Infarction
4. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf

Mar. 16, 2017What are alternate topical treatments for molloscum contagiosum? I usually use imiquimod but it's very expensive and often not covered. I thought I saw something about potassium hydroxide but I don't know how that would be used? details
 

Response: Treatments for molluscum in immunocompetent children with the most evidence include:
-No treatment(1,2)
-Curettage(1,2)
-Cantharidin(1,2)
-Podophyllotoxin(2) (children 10 years and older)
Treatments with limited evidence of benefit include potassium hydroxide, salicylic gel, tretinoin cream, and several others.(1,2)

Cantharidin is available from pharmacies as the brand name Canthacur®. It is applied with the blunt end of cotton swab to lesion only in the office. Application is painless and does not cause bleeding. The area can be washed with soap and water within 2-6 hours. The agent causes small blisters at the lesion site. If lesions persist, treatment can be repeated in 2-4 weeks.(1)

Podophyllotoxin 0.5% solution is the active ingredient of podophyllin, an antimitotic agent; pharmacies can order the brand Condyline®. This solution can be applied at home once or twice daily 3–4 days per week for up to 4–6 weeks. Pain, burning, erosions, pruritus and bleeding may occur. If applied to large areas (>10 cm2) or in high concentrations, systemic absorption may result in neurotoxic effects, limiting use.(4)

The only information availabel for the application of potassium hydroxide comes from the only RCT that wasn’t terribly helpful. In the methods it described(4):
"The parents or caretakers were given verbal and written instructions outlining how to apply the solution to each lesion twice daily with a cotton swab until the lesions showed signs of inflammation. Treatment was to be discontinued if inflammation occurred."
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 116448, Molluscum contagiosum; [updated 2015 Aug 20, cited 16 Mar 2017]; [about 15 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116448&site=dynamed-live&scope=site. Registration and login required.
2. UTD - Molluscum contagiosum
3. Short K, Fuller C, Higgins M. Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum. Pediatr Dermatol 2006 May-Jun;23(3):279
4. CTMA - Viral Skin Infections: Common and Flat Warts

Mar. 17, 2017A woman in her early 60's who has never had chicken pox is wondering about getting Zostavax. Will it be harmful? Should she get chicken pox vaccine instead? details
 

Response: As per Canadian Immunization Guidelines, Canadians 50 years of age and older with no known history of varicella infection are still eligible for herpes zoster vaccination. Patients should not obtain lab confirmation - there are no known safety concerns of herpes zoster vaccine in healthy patients susceptible to varicella virus. Only if lab confirmation of varicella virus has been obtained in the past for other reasons would one vaccinate with two doses of univalent varicella vaccine. (1)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html

Mar. 31, 2017What can be done about the phosphate tablet shortage? details
 

Response: There are liquid sodium phosphate solutions (marketed for laxative use) and contain 4.14 mmol phosphorus and 4.8 mmol sodium per ml (9,10), such that ~4ml is ~ 1 Phosphate-Novartis tablet. The products available at McKesson are Phoslax by Odan (NPN 80000689 ) and Phosphates Solution by PMS (NPN 02230399).(7). Note: while the Phosphate-Novartis tablets have been discontinued(11), a similar product by JAMP is said to be available the end of April.(7)
Also, dietary intake can be increased. Dieticians of Canada phosphorus content of foods available.(14)
References: 1. UpToDate - Evaluation and treatment of hypophosphatemia
2. eCPS (Supplied section all that available)
3. Martindale
4. CTMA Constipation
5. https://www.medicines.org.uk/emc/medicine/25270
6. LNHPD
7. PharmaClik
8. http://sunnybrook.ca/uploads/PTBull36_Phosphate_IV.pdf
9. Phone communication with Christine, Odan Customer Service, 1-800-387-9342, Mar 31, 2017
10. http://www.globalrph.com/phosphate_supplements.htm
11. Phone communication with , Novartis Customer Service, 1-800-465-2244, Mar 31, 2017
12. DPD
13. http://pendopharm.com/product/phosphates-solution/
14. https://www.dietitians.ca/Downloads/Factsheets/Food-Sources-of-Phosphorus.aspx

Mar. 31, 2017I have a patient on Hydroxyurea 500 mg BID (I now reduced it to 500mg od). This to reduce her essential thrombocythemia. Problem is her K+ keeps going above 5.0. She is now on Lasix 40 mg BID just to reduce her K+; there is no other indication for it. I have been able to keep her K+ to 4.8 but now her platelets are slowly rising - now at 682 because of the lower hydroxyurea dose for the last week. Any suggestions as to how to proceed with this case especially keeping her K+ down?? details
 

Patient Age: 68
Patient Sex: F
Medical Problems: Platelets usually 580
highest was 5.5 last week, ECG not conducted
BP good and not dehydrated (drinks plenty of fluids)
atrial fibrillation
no thromboembolism
Medication History: metoprolol, amiodarone, warfarin, ranitidine 150 mg BID, ferrous gluconate, bupropion 150 mg XL, clondine 0.05 mg BID
Response: I found but one case report of hydroxyurea (HU)-associated hyperkalemia in a patient with polycythemia vera.(2) Unfortunately, it’s a typical case report with few details. While the authors describe normalization of potassium levels with discontinuation of the HU, they do not provide any information about how the condition was subsequently managed.
There have been three cases reported via MedEffect(3); however, all of these seem to be tumour lysis syndrome as other metabolic abnormalities (hyperuricemia, hyperphosphatemia, hypocalcemia) were present, which is typical of tumour lysis syndrome.(4) This patient has no other lab abnormalities.
No reason to believe any of the other drugs would be a causative factor, whether by interaction or adverse effect profile was found.(11-13)
Pseudohyperkalemia. There is a decent amount of information regarding pseudohyperkalemia in patients with myeloproliferative disorders.(15-18) In these reports, pseudohyperkalemia was defined as a difference of ≥0.4 mmol/L between serum and plasma concentrations.(16,17) Generally, some blood cells leak potassium that causes a false increase in serum samples, but not plasma samples.(16) If this were the case, the patient's potassium levels would be expected to increase with reduced dose of HU (because her platelets increased) but in fact her potassium levels decreased. Because it is possible furosemide was affecting potassium simultaneously, if simultaneous plasma and serum samples can be ordered, pseudohyperkalemia can easily be ruled in or out.
Should this be a true hyperkalemia,low dose Kayexalate (sodium polystyrene sulfonate – SPS) is reasonable to try. One case series describes use of 15 g once daily (required lowering in some patients) who were experiencing hyperkalemia due to ACEI/ARB therapy.(19) The SPS was added to be able to maintain the ACEI/ARBs. They followed these patients for a mean 14 months; baseline potassium was 6.4 mmol/L which was reduced to 4.6 mmol/L (time span is not noted so close monitoring at the beginning will be important). Some did experience nausea but this subsided with continued use. It is best to use the sorbitol-free product(19), which is powder.(21)
Dietitians of Canada have a good resource of how to maintain a low potassium diet, which includes potassium content of foods without labels (e.g. fruits/vegetables)(20)
Finally, the US has a couple of new products for hyperkalemia that seem to be better tolerated than SPS.(14) One that seemed most appropriate for chronic use is patiromer.(14) This agent isn’t available in Canada. I did contact the Special Access Programme on the off-chance it’s available through them. I haven’t heard back from them and I really do not expect it to be on the program.
References: 1. http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Hydroxyurea_monograph_1Oct2013.pdf
2. Hyperkalaemia associated with hydroxyurea in a patient with polycythaemia vera. Marusic S, Gojo-Tomic N, Bacic-Vrca V, Bozikov V. Eur J Clin Pharmacol. 2011 Jul;67(7):757-8. doi: 10.1007/s00228-010-0962-7. Epub 2010 Dec 14. No abstract available. PMID: 21153897
3. MedEffect Adverse Drug reaction database
4. UTD - Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors
5. UTD - Prognosis and treatment of essential thrombocythemia
6. Buemi M., Fazio M.R., Bolignano D., et al. Renal complications in oncohematologic patients. J Invest Med 2009; 57(8):892-901
7. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
8. DPD
9. NOC database
10. UTD - Treatment and prevention of hyperkalemia in adults
11. DrugDex
12. Stockley's
13. Lexicomp
14. Core Evid. 2017 Mar 23;12:11-24. doi: 10.2147/CE.S129555. eCollection 2017. Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review. Beccari MV1, Meaney CJ1
15. Pseudohyperkalemia in patients with increased cellular components of blood. Sevastos N, Theodossiades G, Savvas SP, Tsilidis K, Efstathiou S, Archimandritis AJ. Am J Med Sci. 2006 Jan;331(1):17-21. PMID: 16415658
16. When is a high potassium not a high potassium? Teh MM, Zaman MJ, Brooks AP, Li Voon Chong JS. J R Soc Med. 2003 Jul;96(7):354-5. No abstract available. PMID: 12835454
17. Pseudohyperkalemia occurring in a patient with chronic renal failure and polycythemia vera without severe leukocytosis or thrombocytosis. Fukasawa H, Furuya R, Kato A, Yonemura K, Fujigaki Y, Yamamoto T, Hishida A. Clin Nephrol. 2002 Dec;58(6):451-4. PMID: 12508968
18. Unexplained hyperkalemia: The tip of the iceberg. Meka NP, Malik YO. Am J Case Rep. 2012;13:125-7. doi: 10.12659/AJCR.883151. Epub 2012 Jun 22. PMID: 23569507
19. Secondary prevention of hyperkalemia with sodium polystyrene sulfonate in cardiac and kidney patients on renin-angiotensin-aldosterone system inhibition therapy. Chernin G, Gal-Oz A, Ben-Assa E, Schwartz IF, Weinstein T, Schwartz D, Silverberg DS. Clin Cardiol. 2012 Jan;35(1):32-6. doi: 10.1002/clc.20987. Epub 2011 Nov 6. PMID: 22057933
20. https://www.healthstandnutrition.com/wp-content/uploads/2011/09/Low-K-diet.pdf
21. eCPS
*Pharmacists letter (drug-induced hyperkalemia)

Mar. 31, 2017Does clonidine need tapering? details
 

Patient Age: 54
Patient Sex: F
Medical Problems: vasomotor symptoms
Medication History: clonidine 0.1 mg OD x 4-5 days then 0.2 mg x 3 days (only was on total 7-8 days)
asked caller and no beta-blocker on board
Response: Clonidine can cause some withdrawal symptoms such as agitation, insomnia, nervousness/anxiety, flushing, nausea, sweating, tachycardia, and tremor if discontinued abruptly.(1,2) The risk increases with: use over 1-2 months, concomitant beta-blocker use, hypertension, cardiovascular disease, daily dose >=1.2 mg.(1) In such cases, a taper of 25% every 2-7 days has been recommended.(1,2)
This patient has only been on the drug for a week and is on a low dose; therefore, tapering is not necessary. That said, if she has some 0.1 mg tablets at home, there is no harm in going to those for a few days before final discontinuation.
References: 1. Geri RxFiles, pg 177
2. Clincial Handbookd of Psychotropic Drugs for Children and Adolescents, 3rd ed. pg 39

Mar. 31, 2017How long after receiving Zostavax do you need to wait before taking prednisone? Dose is for prednisone 10 mg PO OD x 10 days then 5 mg PO OD for 2 months. details
 

Response: The threshold dose of prednisone considered sufficient to interfere with immune response such that Zostavax should not be given (or prednisone started after Zostavax) is 20 mg once daily.(1) Since this patient's dose does not exceed 10 mg, there is no concern.
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html

Mar. 31, 2017A 92 year old patient is not taking anything orally. Can amoxcillin capsules be administered rectally? Or would a compounded suppository work? details
 

Patient Age: 92
Patient Sex: F
Medical Problems: audible crackles, SOB - pneumonia?
Response: The only information available is from an abstract in which ampicillin rectal suppository was compared to amoxicillin suspension administered rectally. While the abstract provides information about plasma concentrations for ampicillin, but not amoxicillin, 86% in the amoxicillin group (n=229) achieved cure plus clinical improvement compared to 89% of the ampicillin group (n=454). There was less perianal irritation in the amoxicillin group (5.2%) than the ampicillin group (12.1%).(1)
Amoxicillin may be sufficiently absorbed when administered rectally.
References: 1. J Int Med Res. 1988 Sep-Oct;16(5):376-85. Clinical evaluation of rectally administered ampicillin in acute otitis media. Bergström BK1, Bertilson SO, Movin G. - access to abstract only.
*Pubmed, Alt ROA resources

Mar. 31, 2017Can breastfeeding be continued when using topical fluorouracil? Any considerations? details
 

Medical Problems: 18 month old infant
some sort of sun spot about the size of the tip of one's pinkie finger
Response: There is no need to discontinue breastfeeding if using topical fluorouracil on small areas.(1,2) Contact of the infant's skin to the treated area needs to be avoided.(1)
References: 1. Lactmed
2. Hale - Medications and Mothers' Milk

Mar. 31, 2017Are there any contraindications, precautions, disease, or drug interactions to be aware of when considering use of evolocumab and adalimumab? Patient is young and high CV risk with uncontrolled LDL on crestor and ezetrol, and cardiologist wants to start evolocumab. Patient is receiving adalimumab for unknown indication. details
 

Response: No drug interactions between evolocumab and adalimumab were identified.(1-4) According to a recent review, "A possible mechanism of interaction with these combinations [two or more monoclonal antibodies] would involve the FcRn-mediated recycling. However, given the total amount of endogenous IgG of 50–100 g, the usual dose of most mAbs of <10 mg/kg is not predicted to affect the total IgG plasma concentration and thus the “salvage pathway” is not affected by the risk of saturation process."(5)
The possibility of additive immunosupppression was considered; however while adalimumab does cause immunosuppression,(4) the target of evolocumab, PCSK9, is not involved in the immune system and there is no indication evolocumab affects the immune system.(3,6)
As such there is no reason to believe any interaction exists between adalimumab and evolocumab.
References: 1. Stockley's
2. Lexicomp
3. eCPS - Repatha
4. ECPS - Humira
5. Pharmacol Res. 2016 Sep;111:592-9. doi: 10.1016/j.phrs.2016.07.015. Epub 2016 Jul 18. Pharmacokinetics interactions of monoclonal antibodies. Ferri N, Bellosta S, Baldessin L, et al.
6. http://www.tandfonline.com/doi/full/10.1080/21678707.2016.1189323?src=recsys
*Pubmed: evolocumab immunosuppression

Apr. 1, 2017How long can a risperidal consta be left out of the fridge? details
 

Response: The Risperdal Consta Kit should be stored under refrigeration, however, if there is no refrigeration available, it can be stored at room temperature (<25 degress C) for 7 days. Once the product is reconsituted it should be used immediately, however it is stable for 6 hours.
References: 1. Risperdal Consta Drug Product Monograph

Apr. 3, 2017I have permethrin 5% prescribed for a 4 month old but my references say not to use in under 2 year. What to use for scabies in 4 month? details
 

Response: Permethrin 5% can be used on infants greater than 2 months, though it is off label use. The hairline, neck, temples, and forehead may be infested in infants and geriatric patients. In these populations, permethrin should also be applied to the scalp and face, sparing the eyes and mouth.
References: 1. UpToDate, treatment of scabies

Apr. 3, 2017I want to treat a 5 year old with rogaine 5%. She has alopecia areata. Any evidence for safety or efficacy? details
 

Patient Age: 5
Patient Sex: F
Medical Problems: alopecia areata
Medication History: failed diprosone cream
Response: Rare cases of hypertrichosis have been associated with topically applied minoxidil.
There is a reported case in the Brazilian literature of generalized hypertrichosis affecting a 5-year-old child, following use of minoxidil 5%, 20 drops a day, for hair loss. The laboratory investigation excluded hyperandrogenism and thyroid dysfunction. Topical minoxidil should be used with caution in children. (An Bras Dermatol. 2016 Jan-Feb;91(1):87-8.)

Hypertrichosis is a common side effect of topical minoxidil treatment in women. Although usually localized to the face, it may occasionally involve limbs and other body areas.

Systemic absorption of the drug is typically minimal with topical therapy, with 1.4% of the applied dose being absorbed. However, hypotheses on the pathogenesis of the diffuse hypertrichosis reaction routinely include systemic absorption, as well as high sensitivity of the follicular apparatus to minoxidil.

In the case of a 2 year old, the excessive dose (both in terms of concentration and daily quantity) in combination with the patient’s low body weight favoured systemic adsorption. Further support for systemic effects are noted in the reported cardiovascular side affects in three patients from 10 to 14 years of age treated for alopecia areata with minoxidil 2% topically twice a day 8. These effects included sinus tachycardia, sensation of palpitation and dizziness.

The efficacy of topical minoxidil in alopecia areata has never been definitively proven. The possibility of systemic absorption contraindicates, in some reasearchers opinion, this treatment in young children, who can develop serious cutaneous or systemic side effects. ( F1000Res. 2013 Oct 28;2:226. doi: 10.12688/f1000research.2-226.v1. eCollection 2013.)
References: 1. PMID: 26982785
An Bras Dermatol. 2016 Jan-Feb;91(1):87-8. doi: 10.1590/abd1806-4841.20164010.
Infantile generalized hypertrichosis caused by topical minoxidil.
2.PMID: 24555107
F1000Res. 2013 Oct 28;2:226. doi: 10.12688/f1000research.2-226.v1. eCollection 2013.
Minoxidil induced hypertrichosis in a 2 year-old child.

Apr. 3, 2017Rabeprazole tablets are enteric coated and I am wondering why? Can they be crushed? details
 

Response: Rabeprazole is enteric coated because it is unstable in acidic media and undergoes pH-dependent decomposition especially rapidly below pH 4-5; therefore it should not be crushed. (1)
Alternative Formulations & Administration: - Capsules: dexlansoprazole, lansoprazole, omeprazole - Open capsules & sprinkle intact granules onto soft, cold food. Swallow immediately; do not crush/chew granules; Suspension from solid dosage form for po or NG tube: use dexlansoprazole, esomeprazole (tablet NEXIUM & some generics, granules), lansoprazole (capsule granules, FASTAB)(2)
References: 1. DPD - apo-rabeprazole monograph
2. RxFiles - Acid Suppression Drug Comparison Chart

Apr. 3, 2017Can a person have the Zostavax injection on the same day they had Prolia? Person is 69 years old. details
 

Medication History: aventyl 25, synthroid 50mcg, zolmitriptan 2.5mg, prolia a few months ago
Response: There are no drug interactions or contraindications for getting zostavax after having the prolia injection.

Unlike other live vaccines, because HZ vaccine is not used for eliciting a primary immune response, it is reasonable to consider HZ vaccine in people receiving low dose immunosuppressive therapy.

Prolia is used with caution in patients with impaired immune systems or using concomitant immunosuppressive therapy; may be at increased risk for serious infections.
References: 1. Pharmacist Letter
2. Micromedex
3. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html
4. lexicomp

Apr. 3, 2017Have you ever heard of using patenolol eye drops in the nostrils? I have an Rx for it and wonder if this is an acceptable way to administer the drops? details
 

Patient Age: 13
Patient Sex: M
Medication History: nasonex, reactin
Response: Olopatadine comes in a nasal spray called Patanase 0.6%. It is used for seasonal allergic rhinitis at 2 sprays in each nostril twice daily.(1) It is not available in Canada. (2)(3)(4)
References: 1. micromedex
2. DPD
3. cps
4. Pharmaclik

Apr. 3, 201715 yo anemic patient taking 35 mg elemental iron tid. He is intolerant to this, is there an injectable version? details
 

Patient Age: 15
Patient Sex: MALE
Medical Problems: 15 yo with anemia
Medication History: 35 mg elemental iron tid
Response: Has patient tried taking iron with a meal to decrease GI side effects? (Will decrease absorption, but may have meal/snack high in vitamin C to slightly increase absorption- will still be decreased overall though)
Yes, a parenteral version is available. Dexiron 50 mg/ml (2 ml vial) is available for IV administration.
IM generally not recommended as it is painful, stains the buttocks, and has variable absorption and case reports of sarcoma (1)
IV Dexiron is the cheapest and most convenient form of IV Iron. Dexiron and Venofer not available for another couple of weeks. Dexiron and the other option Venofer are not available from the manufacturer for at least a few weeks.
Dose for Dexiron:
Iron-deficiency anemia: IV Dexiron
Dose (mL) = 0.0442 (desired hemoglobin - observed hemoglobin) x LBW + (0.26 x LBW)
Desired hemoglobin: Usually 14.8 g/dL
LBW = Lean body weight in kg
This is to be diluted in NS before administering via IV
Max= 1-1.5g/dose
***Initial test dose needed (Sensitivity test)- Administer slow IV >5min of 0.5 mL (25 mg iron), observe >1 hour for sensitivity rxn before giving the remainder. (3)
References: 1- UptoDate
2- Lexicomp Dexiron
3- RxFiles –Iron Management

Apr. 3, 2017I have a 14 year old with generalized anxiety and migraines. She's on nortriptyline 25mg at bedtime. I'd like to start something for anxiety. Was planning on getting a baseline EKG and then start escitalopram (if insurance covers) or sertraline (if escitalopram isn't covered) at low dose and increase slowly to target dose of 10 escitalopram to 100 of sertraline over 6 weeks. Anything else I should be aware of? I discussed risk of serotonin syndrome.' details
 

Medical Problems: headaches
Medication History: nortriptyline 25mg hs
Response: Escitalopram is predicted to increase the exposure to nortriptyline. The serotonin syndrome has, rarely, been seen in patients given SSRIs with tricyclics. Nortriptyline has been associated with QT prolongation or torsade de pointes (mainly in overdose) but an effect is not established, whereas escitalopram has some risk of prolonging the QT interval. Some consider that concurrent use might increase the risk.

Since both citalopram and escitalopram are thought to be among the SSRIs least likely to alter the metabolism of other drugs, escitalopram is likely the best choice among the SSRI's to use with someone also taking nortriptyline. Monitor concurrent use for tricyclic toxicity (dry mouth, sedation, confusion), and adjust the dose if necessary. Some suggest a small initial SSRI dose. Increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia) predispose to QT prolongation: in their presence consider ECG monitoring, which you are doing.

Escitalopram and citalopram are considered weak inhibitors of CYP2D6.
References: 1. Stockleys
2. lexicomp

Apr. 3, 2017Is it ok to crush Onglyza? details
 

Response: The tablets are film-coated(1) and immediate release.(3) While the monograph says not to split or cut, this is due to the absence of kinetic data of altered tablets.(3) This drug does not appear on the Do Not Crush list(2) and the manufacturer was unable to provide any reasons (such as taste/mucosal irritation) to avoid crushing.(2) As such, crushing is reasonable so long as they are crushed immediately prior to administration.
References: 1. eCPS
2. http://www.ismp.org/tools/donotcrush.pdf
3. Phone communication with AST medical information, (question originally emailed to: questions@ASKmedical.ca), Apr 4, 2017
*Alt Route Admin

Apr. 4, 2017Can you crush morphine IR? details
 

Response: Morphine IR can be crushed (2). Manufactuer says there is no specific kinetic/pharmacologic reasons for their warning, but rather it is based on abuse potential (3)
References: 2. ISMP do not crush
3. Manufactuer call to Purdue Pharma

Apr. 5, 2017We were at a nurses’ meeting today and the question came up about aspirin monitoring. What is the recommendation for low dose (81mg OD PO)? – The background to this question is, a resident was on low dose aspirin and she had melena recently (aspirin now on hold) details
 

Response: For low-dose aspirin, there are not any specific recommendations for monitoring, beyond what a patient would already have done. For example:
- Consider monitoring renal function periodically (every 6-12 months) in someone with compromised renal function, or at risk of poor renal function (eg. Diabetics, also on diuretics , other NSAIDs) -- these populations likely already have renal function testing done, so low dose ASA would not impact this. If a person has no risk factors for compromised renal function, then extra testing would not be necessary based on just being on ASA 81mg.
- Iron related lab tests would not be regularly indicated for someone on low-dose ASA. If a person has a history of anemia or GI bleeds / ulcers, then periodic monitoring would be reasonable (every 6-12 months)--otherwise, instructing the patient to watch for blood in the stool will be more effective in detecting a bleed than lab monitoring would be.
- For your patient, it is prudent to discontinue the ASA if a bleed does occur.
- Probably the most important aspect to sometimes re-evaluate is making sure a patient actually requires ASA 81, especially if it's just for primary prevention.
References: 1. Monograph for ASA 81mg
2. Micromedex, aspirin monitoring

Apr. 6, 2017Is there a place to look for metabolites of drugs of abuse? When a NP gets a urine screen back and sees results she often asks if it’s a metabolite of a drug the patient is taking. What about a morphine equivalent chart? details
 

Response: One resource that has fairly comprehensive list of metabolites is drugbank.ca
eCPS has an equivalent table in the dosage section of the CPhA Opioids monograph
Global RPh has two calculators - http://www.globalrph.com/narcoticonv.htm and http://www.globalrph.com/opioidconverter2.htm (for methadone)

Apr. 6, 2017We package bubble packs for long term care about a week in advance so those getting Florinef are at room temperature for ~35 days. The monograph says it can stay at room temperature for 30 days but a New Zealand site says 3 months. Will 35 days be okay? details
 

Response: Florinef is known to be stable up to 30 days at room temperature.(1-3) However, no stability beyond 30 days is available as studies of greater duration were not conducted.(3) It should be noted this product used to be stored at room temperature and storage recommendations were changed in ~2005, not based on reformulation but more sophisticated analysis techniques. (2)
References: 1. Previous phone communication with Marie, medical information, Paladin Labs 1 888-550-6060 #395 5/30/2008
2. Phone communication with Kayla, Paladin Labs, 1-888-550-6060 Jan 24/11
3. Phone communication with Julia, Paladin Labs, 1-888-867-7426 07 Apr 2017

Apr. 6, 2017Any suggestions for alternatives to the IV lasix shortage besides PO lasix? It would be much appreciated to have another alternative to recommend to physicians. details
 

Response: Furosemide is available as an oral solution. Clearly it has a slower onset of effect (30-60 minutes) for diuresis compared to 5 minutes for IV.(6)
There is an available alternative to IV furosemide. Ethacrynic acid is a loop diuretic available as injectable (DIN 00268313).(3) The usual dose is 50 mg or 0.5-1 mg/kg (max 100 mg).(4,5) The problem is this product’s acquisition cost is $545 per dose (vials of 50 mg).(3) It can be irritating at the injection site so if a 2nd dose is required, it should be administered at a new site to reduce the risk of thrombophlebitis. It has a higher risk of ototoxicity than other loops and should be avoided in those with CrCl <10 ml/min.(5)
Unfortunately, the ethacrynic acid is the only other IV diuretic available in Canada.(2)
References: 1. eCPS - CPhA monograph
2. DPD
3. PHarmaClik
4. Ottawa Hospital Parenteral drug Manual
5. https://www.ashp.org/drug-shortages/current-shortages/Drug-Shortage-Detail.aspx?id=636 (including Table 2)
6. Lexicomp

Apr. 6, 2017Can dextromethorphan be used to effectively to treat anxiety accompanied by bouts of screaming and shouting? details
 

Response: A combination product, DM 20 mg/quinidine 10 mg, has been approved in the US for pseudobulbar affect.(2) Pseudobulbar affect is “characterized by sudden, unpredictable and involuntary episodes of crying, laughing, or other emotional displays that are exaggerated relative to or incongruent with the mood and feelings of the patients."(2) There is also very limited evidence of use in autism.(2)
The DM/quinidine product is not approved in Canada.(3) The quinidine is only included to exploit its CYP2D6 inhibition.(2,4)
References: 1. A placebo double-blind pilot study of dextromethorphan for problematic behaviors in children with autism. Woodard C, Groden J, Goodwin M, Bodfish J. Autism. 2007 Jan;11(1):29-41. PMID: 17175572
2. Pharmacol Ther. 2016 Mar;159:1-22. doi: 10.1016/j.pharmthera.2016.01.016. Epub 2016 Jan 28. Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. Nguyen L1, Thomas KL2, Lucke-Wold BP3 PMID 26826604
3. NOC database
4. Lexicomp
*Clinical handbook of psychotropic drugs for children and adolescents, DrugDex, PubMed "dextromethorphan anxiety ";

Apr. 6, 2017We received a prescription for azithromycin 500 mg x 1 day then 250 mg x 1 month. (Prednisone prescribed as well.) What would be the indication for this length of therapy? details
 

Patient Age: 72
Patient Sex: M
Medical Problems: COPD
T2DM
Medication History: Spiriva, salbutamol,
statin, Lantus, metformin, amlodipine

clarithromycin 500 mg BID x 7 days, 10 days ago with prednisone
not sure if hospitalized
Response: Chronic, prophylactic antibiotics have been shown to reduce exacerbations in COPD compared to placebo in patients with moderate to severe COPD.(2,3) Azithromycin has been studied at 250 mg PO OD x 1 year (as well as a pulsed regimen).(3) However, this intervention would be considered after other means of reducing exacerbations have been instituted including inhaled corticosteroids.(3) Furthermore, it seems this patient may be experiencing an exacerbation at this time and prophylaxis was only started in patients who were exacerbation free for at least 4 weeks.(3) Assuming this is an exacerbation that did not respond to clarithromycin, azithromycin is not a good choice. If it is strongly felt the etiology is bacterial, amoxicillin-clavulanate is a better choice in this complicated patient.(1,2) If there is no response within 72 hours, consider sputum culture and reconsider etiology.(2)
References: 1. UTD - Management of exacerbations of chronic obstructive pulmonary disease - Outpatient management of exacerbations of COPD
2. CTC - Chronic Obstructive Pulmonary Disease
3. Herath SC, Poole P. Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD). Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD009764. DOI: 10.1002/14651858.CD009764.pub2.

Apr. 6, 2017A nursing home patient with partial gastric outlet obstruction and severe gastric reflux has been getting dilatation q4wks from surgeon and her pantoprazole dose was increased to 80 mg PO BID yesterday. The surgeon wants to know what can be used for breakthrough reflux. The monograph for Diovol Plus says it's contraindicated when distention is due to partial or complete gastric obstruction. What is the reason for this? If Diovol Plus really can't be used, what else could be tried? details
 

Patient Age: 82
Patient Sex: F
Medical Problems: severe reflux
partial gastric outlet obstruction - not completely emptying, severe gastric reflux
Medication History: pantoprazole started at 40 mg BID, increased to 60 mg BID 2 weeks ago and now surgeon is increasing to 80 mg BID
rosuvastatin 10 mg HS, candesartan 8 mg OD, pregabalin 75 mg BID, Slow K i bid, Symbicort
salbutamol,
PRNs: Gravol 50 mg, Anodan HC suppositories, lactulose, APAP 1000 mg TID PRN, Senokot-S artificial tear
reviewed non-pharmacological strategies. Surgeon wants to know what can use for breakthrough? Diovol? Monograph - Plus - CIs - alkalosis, where disteneion may be due to partial or complete gastric obstruction. Had been on 10 mL TID PRN but d/c and not sure why. Had been on domperidone d/c.
Response: While it is not stated in monographs, it would seem the reason for the contraindication of antacids in patients with intestinal obstruction may be due to risk of bezoar formation, which has been reported in earlier literature.(2-4) Reduced intestinal motility, dehydration, and reduced gastric acid have been proposed as reasons these patients experienced bezoar formation.(2-4) While larger doses are surely to increase risk (4), a report of bezoar formation in a patient taking 45 ml MgO twice per week in combination with a diuretic has been published.(2)
It seems reasonable to try an antacid at reocmmended doses followed by a full glass of fluid; this should be discontinued if it does not provide relief. Possibly bezoar formation can be monitored during dilatations.
References: 1. eCPS
2. Small bowel obstruction caused by a medication bezoar: report of a case. Tatekawa Y, Nakatani K, Ishii H, Paku S, Kasamatsu M, Sekiya N, Nakano H. Surg Today. 1996;26(1):68-70.
PMID: 8680127
3. Intestinal obstruction from medication bezoars. Korenman MD, Stubbs MB, Fish JC. JAMA. 1978 Jul 7;240(1):54-5. No abstract available. PMID: 307067
4. South Med J. 1986 Jul;79(7):917-8. Small bowel obstruction from an antacid bezoar: a ranitidine-antacid interaction? Burruss GL, Van Voorst SJ, Crawford AJ, PMID: 3726597

Apr. 6, 2017I'm wondering if there is any difference in efficacy between chewable and enteric coated aspirin in terms of primary and/or secondary prevention. From what I can tell, chewable aspirin seems like a better choice for acute/emergency situations, but I'm looking more for information regarding long-term use for prevention. Additionally, is enteric coated aspirin much safer in terms of preventing adverse effects like GI bleeds? details
 

Response: The reason for enteric coated ASA is to reduce dyspepsia. Because both formulations contain the same drug, there is no difference in terms of effectiveness for primary/secondary prevention between the two. When taken during a suspected MI, it is preferred to chew ASA for faster absorption; certainly chewables are easier to chew and taste better. The next best option in this case would be a regular tablet though enteric coated can be used if it's all that's available - it may be more difficult to chew.
The risk of GI bleed is a systemic effect of ASA and is not reduced by use of enteric coated products. As stated above, enteric coated products serve to reduce dyspepsia, but not reduce GI bleeding. (1)
References: 1. Canadian Pharmacist's Letter; November 2012; Vol: 19

Apr. 7, 2017Patient experiences leakage of insulin even after holding needle in place for 15 seconds. Would switching to a longer needle help or is there another issue to address? details
 

Patient Age: 50
Patient Sex: M
Medical Problems: T2DM
Medication History: Lantus
Insupen Needles 32G 4mm
Response: The resounding consensus is needle length has no effect. I have outlined some strategies to manage and information that I gathered from these references. There is conflicting information about what angle to hold the pen, but there are several other suggestions. Your patient may already be practicing all these strategies in which case the information may be more helpful (basically reassurance that it’s not typically a problem).

Strategies to reduce leakage
- Leave pen in for 10 seconds to prevent leakage(1,2)
- After removing needle, place finger on site for 5-10 seconds (1)
- Always remove the needle from the pen after injection(1-3); leaving the needles attached can cause air to enter the cartridge and it will take longer to inject the insulin (1) or affect the dose (2)
- Try injecting at 45-degree angle rather than 90 (1)
o however, another says: 4-mm needle should be inserted at 90 degrees, not an angle (2)
- Larger doses may be split to reduce the volume of insulin (2)
- Use needles with thin-wall or extra-thin-wall technology (2,4)
- Direct observation of self-injection is important for those who report frequent skin leakage.(2)

Information about leakage
- Leakage following withdrawal of the needle is not unusual.(1)
o usually the amount is clinically insignificant.(1,2)
- Insulin appearing on the skin after removing needle = backflow (5)
o occurs with both syringes and pens (5)
o occurs with all needle gauges (5)
o occurs with all needle lengths (2,4-6)
o occurs with all body compositions (4,5)
- Studies show backflow is a consistent percentage of the injection such that as the dose increases, the percentage of backflow increases so this does not interfere with dose adjustment. (5)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Diabetes-Insulin-ManagmentTool.pdf
2. http://www.rxfiles.ca/rxfiles/uploads/documents/Insulin-Longer-Shorter-InfoGraphic-RxFiles.jpg
3. Dubois W. Everything you wanted to know about injecting insulin. Diabetes Self Management. [updated 04 Oct 2016; cited 07 Apr 2017] Available at https://www.diabetesselfmanagement.com/managing-diabetes/treatment-approaches/everything-you-ever-wanted-to-know-about-injecting-insulin/
4. Campbell A. Injecting insulin: tips for success. [11 Jul 2016; cited 07 Apr 2017]. Available at https://www.diabetesselfmanagement.com/blog/injecting-insulin-tips-success/
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3380785/
6. http://www.sciencedirect.com/science/article/pii/S0025619616303214
7. http://journals.sagepub.com/doi/pdf/10.1177/0145721716648017
8. https://www.diabeteseducator.org/docs/default-source/legacy-docs/_resources/pdf/research/injectioneducationpracticeguide.pdf?sfvrsn=2

Apr. 7, 2017How long can the client be off the tamsulosin and not end up with urinary retention again? Is there an another option to use? Upcoming cataract surgery and concern with floppy iris syndrome. details
 

Patient Age: 76
Patient Sex: M
Medical Problems: Post CVA several years lives at home. Had significant urinary retention post stroke and now continent on tamsulosin.
Booked for cataract extraction and was told to be off it for a month. has two eyes so will likely be up to three months off the med.
Medication History: Tamsulosin 0.4 mg daily
Senokot S 2 tabs daily
Omeprazole 20mg daily
citalopram 20 mg daily
Response: Bottom line: the most current guidelines state discontinuation of alpha-1 blockers prior to cataract surgery does not prevent intraocular floppy iris syndrome (IFIS). In the case of a patient established on tamsulosin therapy and requiring cataract surgery, mitigating factors lie largely with the surgeon. Switching to a less selective alpha-antagonist would seemingly be a good compromise of risk reduction and maintenance of control of lower urinary tract symptoms (LUTS); however, there is no evidence to support this strategy.
--------------
The half-life of tamsulosin is approximately 14-15 hours2 such that return of urinary symptoms would be expected to start about 48 hours following discontinuation. Other drugs used for LUTS include other alpha-1 blockers, 5-alpha-reductase inhibitors, antimuscarinics in combination with alpha-1 blockers and tadalafil.3 Switching agents prior to surgery is unlikely to be an effective strategy based on pharmacology of some of the other agents but mainly due to the reported long-term effect of tamsulosin on the risk of IFIS.

The effects of tamsulosin on the iris have been reported to occur even several years after discontinuation,2,4-7 likely because some of the effects are irreversible.5,8 Apparently, though, in most cases, the discontinuation had been only 2-14 days prior to surgery.2 Tamsulosin appears to have a greater impact on IFIS than other alpha-1 antagonists5 which could be because it is the only alpha blocker selective for the 1a receptor - which dominates the iris dilator muscle8- and has the greatest affinity for this receptor subtype. However, it needs to be mentioned the estimate of the hazard ratio of tamsulosin compared to other alpha blockers has been wide from study to study which could be because in most studies either the tamsulosin cohort was significantly larger than the others or the cohort in general was small.5 A case-control study found moderate-to-severe IFIS was statistically significantly more common in patients taking tamsulosin (34.3%) than alfuzosin (16.3%) and no alpha blockers (4.4%).9

The most recent ASCRS and AAO Educational Update Statement (2014) makes no recommendation to switch alpha blockers and clearly states, "It is well recognized that simply discontinuing oral α1‐antagonists does not prevent IFIS." 1 The effect is that the surgery may be more difficult but surgical techniques are recommended to overcome the challenges.5,8 Intuitively, one may consider switching tamsulosin to alfuzosin – an alpha blocker not selective for 1a - in hopes that effects are reversible in this particular patient and that alfuzosin will not induce the same changes. Unfortunately, the only research to address this is a small case series published in abstract only.10 These researchers switched patients from tamsulosin to alfuzosin (n=5; 9 eyes) four weeks prior to surgery and found 7 of the 9 eyes to be suboptimally dilated prior to surgery and 7 had undulating iris with subsequent iris prolapse. Of course, given the sample size and uncontrolled nature of this report, one could argue it’s possible the complications were reduced by switching to alfuzosin.

I realize this leaves you in a difficult position. What is known with near certainty is your patient’s LUTS is likely to start worsening within several days of tamsulosin discontinuation. There is also a good chance his use of tamsulosin will complicate the surgery. What is certainly less clear is if tamsulosin discontinuation prior to surgery does reduce the risk of IFIS significantly (we know it doesn’t eliminate the risk). Furthermore it is unclear if substitution with alfuzosin allows for continued LUTS control and a lower risk of IFIS than continued use of tamsulosin. The research to date suggests likely not on both of these last points, but it is too limited to make conclusions. Hopefully with this information you, your patient and the surgeon can reach a best-fit solution.
References: 1. eCPS
2. Clinical Key: BOOK CHAPTER Cataracts. R. Scott Hoffman M.D. Ferri's Clinical Advisor 2017, 251-252.e1
3. Handzel DM, Briesen S, Rausch S, Kälble T. Cataract Surgery in Patients Taking Alpha-1 Antagonists: Know the Risks, Avoid the Complications. Deutsches Ärzteblatt International. 2012;109(21):379-384. doi:10.3238/arztebl.2012.0379. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3371631/#!po=45.0000
4. Prospective masked comparison of intraoperative floppy iris syndrome severity with tamsulosin versus alfuzosin. Chang DF, Campbell JR, Colin J, Schweitzer C; Study Surgeon Group.. Ophthalmology. 2014 Apr;121(4):829-34. doi: 10.1016/j.ophtha.2013.10.031. Epub 2013 Dec 4. PMID: 24314842
5. Cardiovascular and ocular safety of α1-adrenoceptor antagonists in the treatment of male lower urinary tract symptoms. Oelke M, Gericke A, Michel MC. Expert Opin Drug Saf. 2014 Sep;13(9):1187-97. doi: 10.1517/14740338.2014.936376. Epub 2014 Jul 29. Review.PMID: 25073735
6. ASCRS and AAO Educational Update Statement; Intraoperative Floppy Iris Syndrome (IFIS) Associated with Systemic Alpha‐1 Antagonists - Apr 2014 https://www.aao.org/clinical-statement/intraoperative-floppy-iris-syndrome-ifis-associate-2
7. CTC - Norman R, 01 Jun 2015; Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia
8. Storr-Paulsen A, Nørregaard JC, Børme KK, et al. Intraoperative floppy iris syndrome (IFIS): a practical approach to medical and surgical considerations in cataract extractions. Acta Ophthalmol. 2009 Nov;87(7):704-8. PMID 19558575
9. Skorin L. How to avoide intraoperative floppy iris syndrome. Rev Optomet. 2010 Nov; available at https://www.reviewofoptometry.com/article/how-to-avoid-intraoperative-floppy-iris-syndrome
10. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg 2005;31:664-73. PMID: 15899440
11. Blouin MC, Blouin J, Perreault S, et al. Intraoperative floppy-iris syndrome associated with alpha1-adrenoreceptors: comparison of tamsulosin and alfuzosin.J Cataract Refract Surg. 2007 Jul;33(7):1227-34.
12. Jan Teper S, Dobrowolski D, et al. Complications of cataract surgery in patients with BPH treated with alpha 1A-blockers.Cent European J Urol. 2011;64(2):62-66. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921715/
13.Chan T, O'Keefe P, Mather R. Can switching tamsulosin to alfuzosin prevent intra-operative floppy iris syndrome in patients with benign prostate hypertrophy?; Paper #P-00051. Canadian Ophthalmological Society Annual Meeting; Quebec: 2010. http://www.cos-sco.ca/annualmeeting/2010/program/COS2010AbstractBook.pdf
*Dynamed

Apr. 7, 2017What is the final volume of vancomycin injectable when reconstituted? DIN 02394634, 1 g vial. details
 

Response: Reconstitute the 1 g vial with 20 ml sterile water for injection to provide ~50 mg/ml. (1)
References: 1. Product monograph from DPD

Apr. 7, 2017If a baby has failed oral nystatin for thrush, what is the next step? details
 

Medical Problems: 2 month old

oral thrush

22 days ago
9 days ago
Medication History: nystatin oral suspension x 7 days (2 courses; 2nd course started 6 days after the end of the 1st cours).
Response: It is possible the nystatin was not used optimally. Nystatin should be used for 7-14 days (1,3,6) until 2 days after the infection has cleared.(2,3) If the child's symptoms had not been cleared for at least 2 days at the end of the last course, a third course of 1-2 ml QID (3,4,6) for 7 days or until 2 days after symptoms resolution, whichever comes later, can be considered. If the nystatin has been used appropriately, fluconazole 3 mg/kg is listed in pediatric references for oropharyngeal candidiasis in infants one month old and up. (5,7) If the mother has symptoms of candidiasis on her nipples, it may be more effective to use a cream such as clotrimazole or nystatin for greater contact time, though there is nothing to suggest the suspension would not be effective. If the mother does not have symptoms, there is no need to switch from the suspension.
Furthermore, toys, pacifiers, feeding bottles/nipples should be sterilized to prevent re-infection.(1,3)
References: 1. CTMA - Oral Candidiasis
2. http://www.caringforkids.cps.ca/handouts/thrush
3. Dynamed - Oral candidiasis in infants
4. Canadian Pharmacist's Letter 2016; 32(12):321231
5. SickKids drug handbook
6. Bugs and Drugs
7. BNF for children 2016-2017

Apr. 7, 2017I have a patient who cannot tolerate much exercise and I'm trying to figure out if either ivabradine or entresto would be worth trying to improve this? details
 

Patient Age: 83
Patient Sex: M
Medical Problems: CHF, AF, aortic valve stenosis.
EF and NYHF class not available
Never smoked, lived healthy all his life, ran until his hip replacement and then biked well into his 70's.
Medication History: Dig .125 mg daily, Atorvastatin 10mg daily, Diltiazem 120mg daily, ramipril 2.5mg daily, bisoprolol 5mg daily, spironolactone 25mg daily, Furosemide 40mg daily, Warfarin to keep INR btwn 2 and 3
Eltroxin 0.05mg daily
Response: Because of the presence of AF in your patient, ivabradine is not an option. (4,8)
Entresto could be considered, which is discussed below. However, some other tweaks can be made before considering Entresto:
1. Diltiazem worsens exercise tolerance (4,5,7) and therefore should be discontinued. Whether it’s being used for hypertension (though not listed as a medical condition) or AF, other drugs can pick up the slack.
2. The dose of ramipril is not optimal.(6,7) The target dose of ramipril in HF is 5 mg PO BID or 10 mg PO OD. Perhaps his dose has been limited by side effects such as hyperkalemia but this should be investigated.
3. The dose of bisoprolol is not optimal.(6,7) The target dose of bisoprolol in HF is 10 mg PO OD. Again, it is possible this dose has been limited by heart rate, his exercise intolerance and/or others. As such, concentrate on optimizing ramipril first.

Suggest to d/c diltiazem and look into optimizing the others as a first step. If after this his symptoms still persist, consider adding Entresto. Note: Entresto will REPLACE ramipril and ramipril needs to be discontinued at least 36 hours before starting Entresto to reduce the risk of angioedema.(1,8) EDS criteria for Entresto include:
For the treatment of heart failure (HF) with reduced ejection fraction in patients with New York Heart Association (NYHA) class II or III to reduce the incidence of cardiovascular (CV) death and HF hospitalization, if all of the following clinical criteria are met:
• Reduced left ventricular ejection fraction (LVEF) (<40%)
• Patient has NYHA class II-III symptoms despite at least four weeks of treatment with a stable dose of an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor antagonist (ARB) in combination with a beta-blocker and other recommended therapies, including an aldosterone antagonist (if tolerated).
• Plasma B-type natriuretic peptide (BNP) ≥ 150 pg/mL or N-terminal prohormone-B-type natriuretic peptide (NT-proBNP) ≥ 600 pg/mL; or plasma BNP ≥ 100 pg/mL or NT-proBNP ≥ 400 pg/mL levels if the patient has been hospitalized for HF within the past 12 months.
• Patients should be under the care of a specialist experienced in the treatment of HF for patient selection, titration, follow-up and monitoring.
(2)
Based on the extensive HF meds list, likely the first bullet is satisfied. The plasma B-type natriuretic peptide level will need to be investigated. Also the NHYA class will need to be confirmed. One note with Entresto is it caused more symptomatic hypotension than the comparator (enalapril) in the trials.(1)
References: 1. Zack’s presentation Drug Therapy Sep 2016
2. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
3. http://www.onlinecjc.ca/article/S0828-282X(15)00475-4/pdf
4. Clinical Resource, New Drug: Lancora (Ivabradine). Pharmacist’s Letter/Prescriber’s Letter. April 2017.
5. PL Detail-Document, Improving Heart Failure Care. Pharmacist’s Letter/Prescriber’s Letter. February 2016.
6. PL Detail-Document, Target Doses of Meds for Systolic Heart Failure. Pharmacist’s Letter/Prescriber’s Letter. November 2013.
7. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-Heart-Failure.pdf
8. PM from DPD

Apr. 7, 2017We have rx for Kdur 20 mmol which has been d/c. We have Euro K 20 (DIN 02242261). Is this interchangable? details
 

Response: Euro-K 20 would be expected to act similarly as K-Dur as K-Dur is the brand reference(2); however, none of the potassium chloride products are interchangeable.(2)
References: 1. http://formulary.drugplan.ehealthsask.ca/
2. http://www.euro-pharm.com/en/products-detail_c.php?prodName=Euro-K+20&fromSearch=true
3. http://www.euro-pharm.com/en/products-detail_c.php?prodName=Euro-K+600&fromSearch=true
4. http://scp.in1touch.org/uploaded/web/refmanual/Regulatory_Bylaws_Current.pdf

Apr. 7, 2017Wondering if you can help me better understand the possible effects of pregabalin in the developing brain. I treat children and adolescents, and occasionally use pregabalin to treat anxiety when other agents have been found ineffective. A patient found this article: http://fibromyalgiaawareness.info/2017/03/27/clinical-research-finds-neurontin-lyrica-death-sentence-new-brain-synapses/ It certainly is inflammatory and seems to exaggerate concerns, however it claims that pregabalin inhibits new synapses from forming. It's based on this study: http://www.cell.com/cell/abstract/S0092-8674(09)01185-4?_returnURL=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867409011854%3Fshowall%3Dtrue I'm having a hard time differentiating truth from hype. Can you help me understand -- is this something that is being over exaggerated or something that should give me pause before prescribing to the developing brain. One of my colleagues told me, "prevention of excitatory effects is probably a feature and not a bug." details
 

Response: The underlying premise of the article is that inhibiting synapse formation is harmful. Certainly I understand that first impression – wouldn’t one stagnate, or worse, regress if synapses are no longer being formed? How can that not have deleterious effects on cognition/learning/development?

In my reading, it seems part of the pathogenesis of epilepsy (1-4), neuropathic pain (1-4), and possibly anxiety (5 is ‘rogue’ synapse formation. In other words, synapses are being formed uncontrollably (or at least aberrantly), causing disease. So, while the animal studies indicate pregabalin and gabapentin do inhibit synaptogenesis, in this sense they are controlling chaos as opposed to interfering with normal development.

Obviously the brain is an extremely complex organ of which humans maybe understand 1% - and of that I may understand 0.001%! As such, I make no claims that gabapentinoids do not or cannot cause long-term negative effects on neuropsychiatric development. All drugs carry risks and these risks are amplified in the pediatric population due to their intense state of development (of all facets) as well as the dearth of medical studies conducted in them. It always comes down to risk vs. benefit.

This study by no means proves gabapentinoids are harmful to the neurodevelopment of a child or adolescent. To me, it does give reason for pause – that there is much we don’t understand about the body and drugs. For this reason the usual tenets of drug use apply:

- use pharmacotherapy only when non-pharmacological strategies are ineffective
- use the lowest effective dose; if no benefit is documented, discontinue
- treat for the shortest duration possible; if benefit has been achieved, discontinue periodically to assess for ongoing need
References: 1. Dolphin AC. Calcium channel α2δ subunits in epilepsy and as targets for antiepileptic drugs. In: Noebels JL, Avoli M, Rogawski MA, et al, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.
2. Risher M, Sexton H, Risher W, et al. Adolescent intermittent alcohol exposure: dysregulation of thrombospondins and synapse formation are associated with decreased neuronal density in the adult hippocampus. Alcohol Clin Exp Res. 2015 Dec;39(12):2403-13.
3. Toth C. Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf. 2014;5(1):38-56.
4. Eroglu Ç, Allen NJ, Susman MW, et al. The gabapentin receptor α2δ-1 is the neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;139(2):380-392.
5. Baldwin DS, Ajel K, Masdrakis VG, Nowak M, Rafiq R. Pregabalin for the treatment of generalized anxiety disorder: an update. Neuropsychiatr Dis Treat. 2013;9:883-92.

Apr. 11, 2017I have a 69 yo female patient with a history of breast cancer (remission since 2012) wanting to use Vagifem for post-menopausal vaginal atrophy. Is this okay? details
 

Patient Age: 69
Patient Sex: FEMALE
Medical Problems: Post menopausal vaginal atrophy
Breast Cancer (2012)
Medication History: tomoxifen
synthroid
vitamins
asa 81
Response: Product monograph of course contraindicates in women with past or previous breast cancer history. However, in February 2017 The Committee on Gynecologic Practice of the American College of Obstetricians and Gynecologists (ACOG) has issued an opinion in support of vaginal estrogen in breast cancer survivors.

Nonhormonal treatments remain first-line therapy. The committee found that vaginal estrogen usually has minimal systemic absorption and delivers lower doses of estrogen closer to normal menopausal levels. While acknowledging controversy about recurrence risk with the use of vaginal estrogen in women with breast cancer who are receiving aromatase inhibitors, the committee concludes that such women "may benefit" from short-term topical estrogen combined with tamoxifen, followed by a return to aromatase inhibitors. Current data indicate no increased risk for recurrence among women receiving tamoxifen, they write.

The committee also emphasizes an individualized approach and informed decision making, in which women can thoroughly weigh the risks and benefits of vaginal estrogen in coordination with an oncologist.
(1)
The North American Menopasue Society support use in consultation with an oncologist.
(2)
References: 1. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause 2013;20(9):888–902.DOI:10.1097/GME.0b013e3182a122c2

2. Veronica Hackethal. ACOG Supports Vaginal Estrogen in Breast Cancer Survivors. Obstet Gynecol. 2016;127:e93-e96.

Apr. 11, 2017Can I add on a CCB like Adalat for my patient? She really loves grapefruit juice and has a prolonged QT interval. details
 

Patient Age: 30
Patient Sex: FEMALE
Medical Problems: Essential HTN
Prolonged qt- sent to internist
Medication History: Marvelon
Coversyl Plus- responded well but needs additional lowering.
Response: Suggested amlodipine instead as grapefruit interaction is not thought to be clinically significant (1). No QT prolongation for amlodipine. Advised to be extra conservative could start at lower dose and titrate up while monitoring for hypotension and tachycardia, but again this interaction is not thought to be clinically significant (7-16% increase). (1)
References: 1. Stockley's Drug Interactions- Nifedipine and Grapefruit Juice
2. RxFiles- CCBs
3. RxFiles QT Prolongation

Apr. 12, 2017Could you check into the area of meningococcal vaccine in pregnancy? Previously, the polysacharide has been the one recommended. However, with the variety of conjugates now available, there might be more/better information on other suitable options. details
 

Response: One resource suggests conjugated meningococcal vaccine is preferred over polysaccharide in pregnant women(2); however, this statement was not referenced and not found elsewhere. One study has been published containing 103 reports of meningococcal conjugate vaccine exposure during pregnancy to the Vaccine Adverse Events Reporting System, in which no safety concerns were identified.(11)
Recommendations of agencies:
PHAC - "the use of conjugate meningococcal vaccines in pregnancy may be considered" (9) There is no mention of polysaccharide vaccine in pregnancy so perhaps this is an endorsement of the conjugated.
CDC -"pregnancy should not preclude vaccination with MenACWY or MPSV4, if indicated" (4)
WHO- "both conjugate and polysaccharide vaccines are efficacious and safe when used in pregnant women"(10)
References: 1.https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-16-pneumococcal-vaccine.html#a15
2. Clinical Key - Schaeffer -Vaccines and immunoglobulins Benedikte-Noël Cuppers and Christof Schaefer, Drugs During Pregnancy and Lactation, 2.7, 177-192
3. Brigg's
4. https://www.cdc.gov/vaccines/pregnancy/hcp/guidelines.html
5. Elwood C, Immunization in pregnancy. Presentation https://fmf.cfpc.ca/wp-content/uploads/2016/11/T136622_Immunization-in-Pregnancy.pdf
6. UTD - Immunizations during pregnancy - Barss V.
7. Maternal immunization with pneumococcal 9-valent conjugate vaccine and early infant otitis media. Daly KA, Scott Giebink G, Lindgren BR, Knox J, Haggerty BJ, Nordin J, Goetz S, Ferrieri P. Vaccine. 2014 Dec 5;32(51):6948-55. doi: 10.1016/j.vaccine.2014.10.060. Epub 2014 Oct 30. PMID: 25444821
8. Chaithongwongwatthana S, Yamasmit W, Limpongsanurak S, Lumbiganon P, Tolosa JE. Pneumococcal vaccination during pregnancy for preventing infant infection. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD004903. DOI: 10.1002/14651858.CD004903.pub4.
9. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-13-meningococcal-vaccine.html#p4c12a3
10. Wkly Epidemiol Rec. 2011 Nov 18;86(47):521-39. Meningococcal A conjugate vaccine: updated guidance, November 2011. PMID 25702330 http://www.who.int/wer/2011/wer8647.pdf?ua=1
11. Zheteyeva Y, Moro PL, Yue X, et al. Safety of meningococcal polysaccharide-protein conjugate vaccine in pregnancy: a review of the Vaccine Adverse Event Reporting System. Am J Obstet Gynecol 2013;208:478.e1-6.
12. https://mothertobaby.org/fact-sheets/meningococcal-disease-bacterial-meningitis-vaccine-pregnancy/
13. http://www.immunize.org/catg.d/p4210.pdf
14. https://www.cdc.gov/vaccines/hcp/vis/vis-statements/mening.html
15. https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/meningococcal-disease
16. Vaccine. 2012 Jul 6;30(32):4717-8. doi: 10.1016/j.vaccine.2012.04.093. Epub 2012 May 20. Pneumococcal vaccines WHO position paper - 2012 - recommendations. WHO Publication. PMID 22621828

Apr. 13, 2017I have a question about the use of hormones/contraceptive use to delay menstruation. I have a 21 year old female, who was contraindicated for COC-birth control use due to migraines with aura. She had a Mirena IUD inserted a couple of months ago and is returning for follow up at 10am this morning. The issue is that her wedding date falls around her regular menstrual period and we have been trying to find a way to delay it by a few days. Norethisterone is used in the UK, but not here, so I am out of ideas. details
 

Patient Sex: F
Response: For future reference, I often recommend norethindrone (=norethisterone) (Norlutate®) in appropriate patients, based on the UK indication. However, norethindrone is metabolized to ethinyl estradiol (EE); when taking Micronor (norethindrone 0.35 mg daily), the amount of EE generated is negligible. However, in a woman taking 15 mg norethindrone daily, research suggests about 25 mcg EE would be generated.(2)

Unfortunately, as you state, options in this patient are limited. The next best option is based on one very small open-label study in which medroxyprogesterone 10 mg TID taken on days 12 to 25 was as effective as norethindrone 5 mg TID taken on days 12 to 25 at reducing heavy menstrual bleeding.(2) This is a different situation than that of the patient. Theoretically, taking the MPA 2-3 days before the expected onset of bleeding, as one does with norethindrone, should delay bleeding. If the wedding is not before the patient's next cycle, she could experiment beforehand.

Otherwise, I find no other options. NSAIDs taken at therapeutic doses (e.g. naproxen 250-500 mg BID) should reduce bleeding but would not be expected to stop altogether or delay.(4)
References: 1. Lexicomp
2. J Fam Plann Reprod Health Care. 2012 Jul;38(3):148-9. doi: 10.1136/jfprhc-2012-100345. Epub 2012 Jun 12. Safer prescribing of therapeutic norethisterone for women at risk of venous thromboembolism. Mansour D1. PMID 22691698 http://jfprhc.bmj.com/content/early/2012/06/11/jfprhc-2012-100345.full
3. http://www.dorsetccg.nhs.uk/Downloads/aboutus/medicines-management/Other%20Guidelines/Delaying%20menstruation%20during%20holidays.pdf
4. UTD - Management of abnormal uterine bleeding

Apr. 13, 2017Client takes lamotrigine and clobazam. She would like to take doxycycline as her antimalarial. Is this okay? details
 

Medical Problems: travel to malarial area
seizure disorder
Medication History: lamotrigine, clobazam
Response: This is not a problem. While some anticonvulsants induce doxycycline metabolism, neither lamotrigine nor clobazam do.(1-3)
References: 1. Stockley's
2. Lexicomp
3.Updated Malarial Screening Tool, Jun, 2016

Apr. 18, 2017For Raynaud's Syndrome, what can be used to help with extremely red, hot feet / legs? details
 

Patient Age: 58
Patient Sex: F
Medical Problems: Raynaud's Syndrome
Medication History: Diltiazem CD 120mg Daily
Atorvastatin 40mg Daily
Rabeprazole 20mg Daily
Response: The evidence for pharmacological treatment of Raynaud’s phenomenon (RP) is quite weak. Nonetheless, dihydropyridine calcium channel blockers (DHP CCB) are considered more effective than non-DHP CCBs. (1-3) As such, it may be advantageous for your patient to be switched to nifedipine XL (30-120 mg daily), felodipine (5-10 mg daily) or amlodipine (5-10 mg daily). Typically symptoms of RP are triggered by cold or emotional stress. (1-3) If she has regular exposure (e.g. the outdoor temperature triggers attacks and she goes for walks daily at the same time), it may be helpful for her to take the dose 30-60 minutes before encountering the trigger. The other consideration is perhaps the red, hot feet are indicative of an underlying pathology also related to the RP symptoms.

Agents with even less evidence include phosphodiesterase-5 (PDE-5) inhibitors, prazosin and topical nitrates. Prazosin is likely to cause more problems with your patient’s BP than the diltiazem and PDE-5 inhibitors may be cost-prohibitive. Dosing is as follows1,3:
PDE-5 inhibitors: sildenafil 50 mg PO BID; vardenafiil 10 mg PO BID; or tadalafil 20 mg every other day or 5 mg PO once daily
topical nitrate ointment 2%: ¼ to ½ inch applied topically once daily
prazosin: 1-2 mg PO BID

I’m sure your patient is well-versed on the non-pharmacological methods but perhaps something in here she has not tried (1-3):
- minimize cold exposure; avoid sudden temperature changes and cold breezes
- dress warmly (including head and neck) and use warming devices in mitts/boots
- smoking cessation if applicable
- during attacks, vasodilation can be increased by:
- placing hands under warm water
- promoting distal blood flow to fingers by swinging arms vigorously (windmill effect) or raising arms above shoulders and forcefully swinging across body
- avoid carrying bags by handles, which may reduce blood circulation to fingers
- consider using general relaxation techniques to minimize emotional stress
References: 1. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. Roussin A. Raynaud’s phenomenon; [updated 01 Mar 2017; cited 18 Apr 2017].Available from: https://www.e-therapeutics.ca/
2. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 115788, Raynaud phenomenon; [updated 18 Aug 2016, cited 18 Apr 2017]; [about 11 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=115788&site=dynamed-live&scope=site. Registration and login required.
3. Rothaus C. Rayaud’s phenomenon. Now@NEJM. 11 Aug 2016; cited 18 Apr 2017. Available at http://blogs.nejm.org/now/index.php/raynauds-phenomenon/2016/08/11/?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+Nownejm+%28Now%40NEJM%29
*CPG

Apr. 19, 2017Patient brought these medications from Mexico -- "ASIP" and "ASMAPRET" -- any idea what they are? details
 

Response: 1. I've searched every variation of what those names look like, and cannot find anything. Verify spelling, try to get dosage and milligram strength to help.

Asipral = azithromycin in Chile
Asmapax = ephedrine + theophylline in the UK
Aspmapen = theophylline in Brazil
(4)
References: 1. MIMS
2. Lexi-international
3. Google search
4. Micromedex
*http://www.who.int/selection_medicines/country_lists/Mexico_medicamentos2009.pdf, http://www.saludymedicinas.com.mx/directorio-de-servicios/medicinas/

Apr. 20, 2017A patient is getting Prolia today. Can she get Zostavax in the next few days? details
 

Response: Denosumab acts on a receptor called RANKL, which is related to TNFα;(1) other drugs that act on TNFα do cause immunosuppression. However, the fact the receptors are related does not mean they have the same action. No precautions or contraindications are available in monographs or other literature with respect to denosumab and live vaccines.(2-6) The manufacturer has been contacted in the past regarding any concerns of denosumab with live vaccines told simply that in the trials participants were not told to avoid live vaccines(7); however, there is also no data on how many participants did receive live vaccines during the trials and their outcomes. There is not enough evidence to avoid vaccination (live or otherwise) in patients on denosumab but at the same time, it is something to monitor in hopes of finding some more definitive information. (1)
References: 1. http://www.hindawi.com/journals/scientifica/2013/125705/
2. AHFS
3. PubMed
4. Lexicomp
5. DrugDex
6. eCPS
7. Phone communication with Valerie, Amgen Medical Information, Jan 21, 2016 1-866-50AMGEN (502-6436)

Apr. 20, 2017Have you seen anyone having trouble with discontinuing Cymbalta being switched to fluoxetine? details
 

Response: Discontinuation syndrome of antidepressants is typically inversely related to half-life.(3) Compared to other SSRIs and SNRIs, duloxetine has a relatively short half-life at 8-19 hours.(1,2) For someone having trouble tapering, switching to fluoxetine is a viable management strategy.(2,4)
References: 1. Lexicomp
2. Clinical Handbook of Psychotropic Drugs
3. Canadian Pharmacist's Letter; March 2016; Vol: 32
4. Kelly K, Posternak M, Jonathan EA. Toward achieving optimal response: understanding and managing antidepressant side effects. Dialogues Clin Neurosci. 2008;10(4):409-418. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181894/

Apr. 20, 2017Does chronic benign neutropenia cause immunosuppression and is thus an issue with receiving Zostavax. details
 

Response: Those with chronic benign neutropenia do not have an increased risk of infection.(1,5) As such, chronic benign neutropenia is not a reason to withold the Zostavax.
References: 1. UTD - Approach to the adult with unexplained neutropenia
2. UTD - Management of the adult with non-chemotherapy-induced neutropenia
3. https://www.hawaii.edu/medicine/pediatrics/pedtext/s11c08.html
4. http://asheducationbook.hematologylibrary.org/content/2012/1/174.full
5. http://www.clinicaladvisor.com/critical-care-medicine/neutropenia/article/586570/

Apr. 20, 2017I have a patient with a sulfa allergy. Is this okay with Proctol, which contains framycetin sulfate? details
 

Medical Problems: allergy to sulfa antibiotic
Response: Sulfa allergy refers to sulfonamide antibiotic or sulfonamide non-antibiotic reactions; while hypersensitivity reactions can be experienced following expsoure to sulfites and sulfates, they are not cross-sensitive to sulfa antibiotic or sulfa non-antibiotics.(1)
References: 1. Lexicomp - Sulfonamide Antibiotic Allergy (Drug Allergy and Idiosyncratic Reactions)

Apr. 20, 2017What is the evidence for use of phenytoin in trigeminal neuralgia? Are there any guidelines or studies for typical doses used or doses with effectiveness? Studies that include when a patient is on carbamazepine as well possibly. Would like some evidence to help support what kind of doses should be using for this indication? details
 

Medical Problems: uncontrolled trigeminal neuralgia
Medication History: Carbamazepine 600 mg BID, gabapentin 600 QID and phenytoin added on the weekend (loaded with IV 1500 mg, then has been on 300 mg IV BID since April 16).
Response: The American Academy of Neurology/European Federation of Neurological Societies practice parameter on treatment of trigeminal neuralgia consider carbamazepine (CBZ), oxcarbazepine (OXCB), and lamotrigine (LMG) as agents with evidence to support use in TN.(1) The following are considered to have insufficient evidence to support or refute efficacy: clonazepam, gabapentin, phenytoin (PHT), valproate, IV medications.(1)

RCTs are available for CBZ, OXCB, and LMG, whereas only uncontrolled evidence is available for PHT. The evidence supporting PHT is based on three uncontrolled studies involving a total of 30 patients. (2-4) Nearly all patients took 300 mg daily, though up to four took 400 mg daily. Of the 30 patients, 16 experienced complete pain relief, 7 partial pain relief, and 6 no effect.

I was unable to locate any case reports/studies of CBZ + PHT used for trigeminal neuralgia to give dosing guidelines with the combination. In general, when CBZ has been added to PHT, it has had variable effects on PHT levels; when PHT has been added to CBZ, CBZ levels tend to decrease and levels of the active metabolite, CBZ-10,11-epoxide (also responsible for toxicity) have increased.(5) As such, CBZ dose may need to be increased to maintain the current analgesic effect, but this is at the risk of greater adverse effects (more than additive). While in some studies LMG has not affected CBZ levels, in a study of three patients, it increased CBZ-10,11-epoxide without affecting CBZ levels; two of these patients developed symptoms of toxicity.(5)

Based on the greater level of evidence and potentially less complicated interactions with CBZ, LMG may want to be considered. Unfortunately, I do not have access to the paper in which LMG was added to CBZ. According to the abstract, patients were maintained on steady state CBZ and LMG was titrated from 50 to 400 mg/day.(6) There is no information available as to adjustment of CBZ or if all patients achieved the 400 mg daily LMG dose. UpToDate suggests for patients taking enzyme inducing drugs, including CBZ, to start LMG at 50 mg daily, titrating upward as needed to 100 mg daily at week 3, 200 mg daily at week 5, 300 mg daily at week 6, and 400 mg daily at week 7.(7) This is a much slower titration than the study above considering the combination was only assessed for 2 weeks in the study.
References:
1. Gronseth G, Cruccu G, Alksne J, et al. Practice parameter: the diagnostic evaluation and treatment of trigeminal neuralgia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the European Federation of Neurological Societies. Neurology. 2008 Oct 7;71(15):1183-90
2. Iannone A, Baker AB, Morrell F. Dilantin in the treatment of trigeminal neuralgia. Neurology 1958; 8:126–8.
3. Braham J, Saia A. Phenytoin in the treatment of trigeminal and other neuralgias. Lancet 1960; 2:892–3.
4. Chinitz A, Seelinger DF, Greenhouse AH. Anticonvulsant therapy in trigeminal neuralgia. Am J Med Sci 1966; 252:62–7.
5. Baxter K (ed), Stockley’s Drug Interactions. [online] London: Pharmaceutical Press (accessed 21 Apr 2014); available at http://www.medicinescomplete.com. Subscription required.
6. Zakrzewska JM, Chaudhry Z, Nurmikko TJ,et al. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain. 1997 Nov;73(2):223-30.
7. Bajwa Z, Ho C, Khan S. Trigeminal neuralgia. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 21 Apr 2017. Available from www.uptodate.com. Subscription and login required

Apr. 20, 2017What is the optimal anti-coagulation regimen for someone with antiphospholipid syndrome? Received a prescription for Arixtra 10mg and all McKesson carries is 2.5 and 7.5 mg, which means she has to inject herself twice daily. Is there a 10 mg syringe? details
 

Patient Age: 34
Patient Sex: F
Medical Problems: kidney function normal
clotting disorder but until recently not clinically symptomatic
tested positive for lupus anticoagulant markers but no official dx Lupus
no weight change
Medication History: failed on warfarin, tinzaparin (during pregnancy), Xarelto (i.e. throws clots), then back on tinzaparin in Nov 2016 - threw several clots
Dec 2016 - started fondaparinux 7.5 mg + Plaquenil (not tolerating so stopped)
last week said bumped up to 10 mg (maybe bc Plaquenil d/c?)
Response: This patient did not disclose the actual bleeding disorder, though her history suggests it may be antiphospholipid syndrome (APS).(8) As such, the following information pertains to APS. Secondary thrombosis prophylaxis is usually undertaken with warfarin(5,6,8); whether the target INR should be 2.5 or 3.5 is under debate.(6,8) This is one area that could be investigated. Following warfarin, therapies typically go to heparins or direct acting anticoagulants(6,8), though trials are ongoing, but none have been published.(8) No discussion of management following failure of all three of these agents was found. Indeed, only one case report of fondaparinux for APS was found (10); the patient, an adolescent, was given 7.5 mg daily. 7.5 mg daily is the VTE treatment dose of fondaparinux for patients weighing 50-100 kg; 10 mg is treatment dose for those > 100kg (2)
Other agents are discussed including hydroxychloroquine (HCQ),(6) which is thought to reduce thrombosis and considering many patients with APS have concurrent lupus, it is a reasonable agent. Otherwise, biologics such as rituximab may be considered, though immunotherapy is only considered in those who need them for other reasons (e.g. lupus nephritis.(5,6) Immunotherapy does not provide any carry-over effect so needs to be taken on a long-term basis along with anticoagulation (in those who have already experienced a VTE.(5)
The treatment course this patient has followed seems very logical. There is also some logic to increasing fondaparinux after discontinuing HCQ, since HCQ could have some VTE prophylactic properties. As such, nothing revolutionary can be recommended. Perhaps the patient was not adherent with previous treatments and the requirment for two injections per day could motivate her to be adherent? This should be investigated for all of the agents. Also, her intolerance of HCQ should be explored to see if it could be managed and/or if it would be something expected to abate with time. Again, she may be more willing to put up with these effects if it means reducing the number of injections. Finally, what about considering a DOAC with a different MOA? Dabigatran has a different MOA to that of rivaroxaban, which has the same MOA of fondaparinux.(2) Certainly there is no evidence to suppport this strategy.
References: 1. DPD
2. eCPS
3. Phone communication with GND Distribution (how answered when called Aspen PharmaCare, who took over Arixtra in Jan 2017) 1-877-827-1306, Apr 20, 2017
4. [Recurrent thromboembolisms despite full anticoagulation in a patient with antiphospholipid syndrome]. Wernicke S, Selleng K, Felix SB, Greinacher A, Hammer F. Internist (Berl). 2017 Mar 6. doi: 10.1007/s00108-017-0211-6. [Epub ahead of print] German. PMID: 28265683
5. Antiphospholipid syndrome. Cervera R. Thromb Res. 2017 Mar;151 Suppl 1:S43-S47. doi: 10.1016/S0049-3848(17)30066-X. PMID: 28262233
6. Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from the General Population? Legault KJ, Ugarte A, Crowther MA, Ruiz-Irastorza G. Curr Rheumatol Rep. 2016 May;18(5):26. doi: 10.1007/s11926-016-0573-0. Review. PMID: 27032789
7. RxTx - CTC - Venous Thromboembolism Jan 2017. Wells P, Forgie M.
8. http://thrombosiscanada.ca/?page_id=18# (each identified thrombophilias)
9. Safety and efficacy of oral direct inhibitors of thrombin and factor Xa in antiphospholipid syndrome. Noel N, Dutasta F, Costedoat-Chalumeau N, et al. Autoimmun Rev. 2015 Aug;14(8):680-5. doi: 10.1016/j.autrev.2015.03.007. Epub 2015 Apr 9. Review. PMID: 25864630
10. Use of fondaparinux in a patient with antiphospholipid antibody syndrome and heparin-associated thrombocytopenia. Holtan SG, Knox SK, Tefferi A. J Thromb Haemost. 2006 Jul;4(7):1632-4. No abstract available. PMID: 16839370

Apr. 20, 2017Can topical tretinoin be used three times weekly for molluscum contagiosum in children? details
 

Medication History: 5% KOH and 0.05% tretinoin similar lesion clearance at 4 weeks
Small RCT without blinding (n=50)
Tx's applied HS over lesions.
Mean lesions at baseline: 9.48 vs. 8.35 (ns) (KOH vs. tret)
At 4 weeks: 1.47 vs. 2 (ns) (KOH vs. tret)
erythema in almost all, erosion in 31% KOH vs. 19% tret; burning about 20% all; edema 26% vs 0%; itching 16% vs. 31%
(7)
Response: Treatments for molluscum in immunocompetent children with the most evidence include:
- no treatmet(1,2)
-curettage(1,2)
-cantharidin(1,2)
Treatments with limited evidence of benefit include the potassium hydroxide, salicylic gel, tretinoin cream, and several others.(1,2)
Tretinoin has been found to be as effective as potassium hydroxide when applied as 0.05% cream at bedtime for 4 weeks(7) and was less effective than 10% benzoyl peroxide when applied BID for 4 weeks.(6) An uncontrolled trial found at 12 months children who were treated for molluscum contagiosum (including 14 treated with tretinoin) had similar outcomes to those not treated.(5) Adverse effects of tretinoin include erythema, erosion, burning, and itching.(7)

Cantharidin is available from pharmacies as the brand name Canthacur®. It is applied with the blunt end of cotton swab to lesion only in the office. Application is painless and does not cause bleeding. The area can be washed with soap and water within 2-6 hours. The agent causes small blisters at the lesion site. If lesions persist, treatment can be repeated in 2-4 weeks.(1)
References: 1. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 -2017. Record No. 116448, Molluscum contagiosum; [updated 2015 Aug 20, cited 16 Mar 2017]; [about 15 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=116448&site=dynamed-live&scope=site. Registration and login required.
2. UTD - Molluscum contagiosum
3. Short K, Fuller C, Higgins M. Double-Blind, Randomized, Placebo-Controlled Trial of the Use of Topical 10% Potassium Hydroxide Solution in the Treatment of Molluscum Contagiosum. Pediatr Dermatol 2006 May-Jun;23(3):279
4. CTMA - Viral Skin Infections: Common and Flat Warts
5. Pediatr Dermatol. 2015 May-Jun;32(3):353-7. doi: 10.1111/pde.12504. Epub 2015 Jan 30. Molluscum contagiosum: to treat or not to treat? Experience with 170 children in an outpatient clinic setting in the northeastern United States. Basdag H1, Rainer BM1, Cohen BA1.
6. 10th World Congress on Pediatric Dermatology meeting abstract (Pediatric Dermatology 2004;21(3):399) as referenced in Cochrane review (Cochrane Database Syst Rev 2009 Oct 7;(4):CD004767)
7. Kathmandu Univ Med J (KUMJ). 2011 Oct-Dec;9(36):291-4. Comparative study of 5 % potassium hydroxide solution versus 0.05% tretinoin cream for Molluscum Contagiosum in children. Rajouria EA1, Amatya A, Karn D.

Apr. 20, 2017Is there an interaction between Malarone and St. John's wort? details
 

Response: No. St. John's Wort potentially interacts with chloroquine, mefloquine and doxycycline (CYP3A4 substrates), but not Malarone.(1)
References: 1. Travel Clinic Nurses' Tool updated 2016 Jun

Apr. 21, 2017We have a patient with pruritus due to liver failure. I would like to use sertraline but it seems it's place in therapy is after standard treatments have failed, which include cholestyramine, rifampicin, naltrexone. Can you put together a list of pros and cons for these agents? For instance rifampicin may not even be available. I found out naltrexone would cost $230/30 tablets and client could not afford that. If evidence is overwhelming to use these agents first, that is what we'll do. I just want to make a recommendation to the MD. details
 

Medical Problems: liver ca
poor renal function
liver failure
Response: Pros and Cons of Cholestyramine, Naltrexone, Rifampicin and Sertraline for pruritus:

Cholestyramine:
-Is an effective first-line agent because of a favorable safety profile and extensive use.
-Overall, there have been few randomized trials of cholestyramine for cholestasis-associated pruritus. (5) Its use is not supported by overwhelming evidence as there are only two trials and they included 18 patients total. (11, 2).
-The effective dose of cholestyramine ranges from 4 to 16 grams per day, divided QID. Dosing can start as 30-60 minutes before breakfast and 30-60 minutes after breakfast. I’m not sure what is easier to accommodate; if it’s easier to get a nurse there after 2 meals, I would change this to 30-60 minutes after breakfast and lunch. The rationale to the 2 doses surrounding breakfast is that in patients with an intact gallbladder, this dosing may enhance the excretion of the pruritogens, which presumably accumulate in the gallbladder during the overnight fast.(12) Of course, any other drugs need to be separated by 4-6 hours. Medication adherence can be a significant problem as cholestyramine can be unpalatable, and induce constipation.

Rifampin (rifampicin)
— More evidence, but still very limited: 61 patients have been evaluated among 3 RCTs and 2 randomized crossover trials. (11) Several reports have demonstrated improvement in cholestatic pruritus with rifampin (5, 7, 8]. In a meta-analysis of five randomized crossover trials with 61 patients, during treatment with rifampin, 47 patients (77 percent) reported complete or partial resolution of pruritus, whereas 12 patients (20 percent) reported complete or partial resolution of pruritus while receiving placebo or alternative medication. (8)
-It is given as 150 to 300 mg twice daily but once daily dosing can be initiated and is more convenient. A 34 day supply is ~$45. Rifampin is EDS only for treatment of non-TB mycobacterium infections.

Naltrexone:
-Opioid antagonists- Opioid antagonists should not be used in patients with liver failure, or severe liver dysfunction (1).
Naltrexone is contraindicated in liver failure (14);
- There is somewhat more evidence, however, it combines all opioid antagonists (buprenorphine, nalmefene, naltrexone and naloxone); 173 patients have been evaluated in over 10 trials. (11)
- Adverse effects: dizziness, nausea, vomiting, headache, abdominal cramping (13)
- Certainly something to consider is this agent will not be able to be used in combination with opioids if they would be something considered in the future
- Dosing is once daily, which is convenient
- A 34-day supply ~295. (I based this on McKesson pricing and added the store mark-up and dispensing fee. The acquisition price is $233/30 tabs so perhaps that is what the pharmacist was quoting. Or, they don’t charge the extra fees.)

Sertraline (Full formulary):
-Used in pruritus refractory to standard treatment —Switching to sertraline at bedtime can be tried if other measures fail (based on the European Association for Study of Liver Disease).
— Case series and a small controlled trial have suggested a possible benefit from selective serotonin reuptake inhibitors. Evidence is based on a randomized cross-over trial of 12 patients. (11)
Sertraline (75 to 100 mg daily) was effective in a retrospective analysis of a group of patients with primary biliary cholangitis (9), and in a small randomized crossover trial of patients with pruritus due to various forms of liver disease. (10)
References: 1. Imam MH et al. Pathogenesis and management of pruritus in cholestatic liver disease. J Gastroenterol Hepatol. 2012 Jul;27(7):1150-8
2. Datta DV et al. Treatment of pruritus of obstructive jaundice with cholestyramine. Br Med J. 1963;1(5325):216
3. Kuiper et al. The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: results of a double-blind, randomized, placebo-controlled trial. Hepatology. 2010;52(4):1334
4. The pruritus of cholestasis. 2005 Dec;43(6):1078-88. Epub 2005 Oct 6.31, Wiertelak EP et al. Cholecystokinin antianalgesia: safety cues abolish morphine analgesia. Science. 1992 May;256(5058):830-3.
5. Tandon P et al. The efficacy and safety of bile Acid binding agents, opioid antagonists, or rifampin in the treatment of cholestasis-associated pruritus. Am J Gastroenterol. 2007;102(7):1528. Epub 2007 Mar 31.
6. Bunchorntavakul C, Reddy KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. 2012 May;16(2):331-46.
7. Podesta A et al. Treatment of pruritus of primary biliary cirrhosis with rifampin. Dig Dis Sci. 1991;36(2):216.
8. Khurana S, Singh P. Rifampin is safe for treatment of pruritus due to chronic cholestasis: a meta-analysis of prospective randomized-controlled trials. Liver Int. 2006 Oct;26(8):943-
9. Browning J et al. Long-term efficacy of sertraline as a treatment for cholestatic pruritus in patients with primary biliary cirrhosis. Am J Gastroenterol. 2003;98(12):2736.
10. Mayo MJ et al. Sertraline as a first-line treatment for cholestatic pruritus. Hepatology. 2007;45(3):666
11. DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - 2017. Record No. 906262, Cholestatic pruritus; [updated 2016 Aug 25, cited 24 Apr 2017]; [about 11 screens]. Available from http://search.ebscohost.com/login.aspx?direct=true&db=dnh&AN=906262&site=dynamed-live&scope=site. Registration and login required.UTD
12. RxTx - CTC:from CPhA
RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2016. Chronic Liver Diseases; [cited April 24/17].Available from: https://www.e-therapeutics.ca/.
13. PM - ReVia

Apr. 21, 2017What is the maximum volume of a medication that can be given rectally? details
 

Response: While there appears to be no specific data, articles on rectal administration of liquids (1-3,5) have been citing a 1991 article suggesting 10-25 ml can be retained without difficulty.(4) Another suggests keeping volumes under 60 ml prevents spontaneous expulsion.(5)
References: 1. Palliative Care Formulary 5
2. PL. Detail-Document, Giving Meds by Alternative Routes. Pharmacist's Letter/Prescriber's Letter. February 2015.
3. Davis MP, Walsh D, LeGrand SB, et al. Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions. Support Care Cancer. 2002 Mar;10(2):117-38. Epub 2001 Nov 9. PMID 11862502
4. van Hoogdalem E, de Boer AG, Breimer DD. Pharmacokinetics of rectal drug administration, Part I. General considerations and clinical applications of centrally acting drugs. Clin
Pharmacokinet. 1991;21(1):11–26
5. Warren DE. Practical use of rectal medications in palliative care. J Pain Symptom Manage. 1996 Jun;11(6):378-87. PMID 8935142

Apr. 21, 2017Are community pharmacies able to administer the yellow fever vaccine? details
 

Response: According to the Public Health Agency of Canada website, you must be a designated Yellow Fever Vaccination Center to aquire the vaccine. For more information on becoming a designated center please see the Public Health Agency of Canada website (1).
References: 1. http://www.phac-aspc.gc.ca/tmp-pmv/yf-fj/pro-eng.php

Apr. 21, 2017Can you provide a compounding recipe for a fluconazole suspension? details
 

Response: Fluconazole has a solubility in water of 8 - 10mg per mL and is also soluble in ethanol. The injection is usually formulated in 0.9% Sodium Chloride and has a pH of 4 - 8.
Fluconazole oral liquid is available in some countries. For small doses the injection can be given orally. Unit doses can be packed into oral syringes.

Yamreudeewong et al (1)1 prepared a 1mg per mL oral liquid by triturating Diflucan® tablets with deionised water. This preparation is chemically stable for 15 days at 4 and 23°C in glass vials. The potential for microbial growth was not assessed.
Sterile water should be used for this preparation and a 7 day expiry date is suggested.
Compatibility with flavours and syrups has not been assessed so a simple solution should be prepared as above. Flavour can be added to the dose just prior to administration. Refrigeration is important as an antimicrobial preservative is not included in the preparation.
(1)
References: 1. http://www.pharminfotech.co.nz/manual/Formulation/mixtures/fluconazole.html
*AHS Compounding manual

Apr. 24, 2017A product called Sleep Harmony (NPN 80063986) seems to just contain lavendar but it says it's active ingredient is Silexan, a patented lavendar oil. Are there any drug interactions with Silexan? details
 

Response: Silexan is simply a patented ingredient that only contains lavendar(1-3), such that interactions only apply to lavendar. Lavendar should be used with caution in people on antihypertensives as it may have additive hypotensive effects and in people already taking CNS depressants, especially barbiturates, benzodiazepines, and chloral hydrate.(3)
References: 1. http://www.sleepharmony.ca/product-information
2. http://www.sleepharmony.ca/about
3. Natural Medicines

Apr. 24, 2017How much calcium is in the "atorvastatin calcium" tablets? details
 

Response: The amount of calcium in an 80 mg tablet of Lipitor (regardless of brand) on account of the atorvastatin calcium is 2.65 mg.(1) The amount in a 10 mg tablet is 0.33 mg.(1) Some brands also contain calcium carbonate in the non-medicinal ingredients.(3) An 80 mg tablet, including the drug and the non-medicinal ingredients would not likely be more than ~ 200 mg. There are 13 other non-medicinal ingredients in a Lipitor tablet, but for the sake of argument, let’s say 120 mg of the tablet (200 mg total tablet size – 80 mg atorvastatin calcium) is calcium carbonate; since calcium carbonate is 40% elemental calcium(4), this would add an additional 48 mg. However, as pointed out above, this is a gross overestimation and one should not rely on atorvastatin tablets as a source of calcium.
References: 1. Martindale
2. http://www.ptable.com/
3. eCPS - Lipitor
4. eCPS - CPhA Calcium salts

Apr. 24, 2017Would restasis eye drops be an issue for someone receiving the Zostavax vaccine? details
 

Response: Cyclosporine A, when applied ophthalmically twice daily, is not quantifiable in the blood even after 12 months' use.(1) Considering this means the concentration is at least 6550 times lower than those measured during systemic therapy for non-life-threatening indications, there is no concern of immunosuppression and this patient can receive Zostavax.
References: 1. eCPS - Restasis

Apr. 24, 2017The nurses from the mines up north are asking for naloxone kits (we send them naloxone vials). Is there a special program for this? details
 

Response: Kits can be ordered from the Control Group for $31 each.(1) They have a phone number on their order form that can be called for information about current stock.(2)
References: 1. https://www.skpharmacists.ca/pharmacists/resources/naloxone
2. https://docs.google.com/forms/d/e/1FAIpQLSdVBaFjk-gvjmRWO09XWNf47MLp7Uifm3dF8ZAV_iUC-CX9cQ/viewform?c=0&w=1

Apr. 24, 2017Can Ketorolac be used safely / effectiveinly in the neurosurgical population? details
 

Response: •There are no trials
• Most papers I read don’t include NSAIDs in the discussion of SAH-induced headache recommended managemet (2-4) and one paper recommended against NSAIDs post-SAH. (5)
• One paper had a discussion of pain management for headaches; the discussion of headache following SAH did not include NSIDs. (6) However, it listed ketorolac and diclofenac in the table as treatment options for postoperative headaches and SAH. The references for this were:
i. a retrospective stud (7) of gabapentin for SAH headache management in which ‘other common analgesics were mainly acetaminophen and occasionally ketorolac’ is the only mention of ketorolac; the lead author of the study (7) is also lead author of the review.(6)
ii. a review of pain management following intracranial surgry (4) This paper does mention NSAIDs in the discussion of nonopioid analgesics and does include ketorolac in the dosing table; however, the authors do not include NSAIDs in the recommendations section.
References: 1. Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage. Niemi T, Tanskanen P, Taxell C, Juvela S, Randell T, Rosenberg P. J Neurosurg Anesthesiol. 1999 Jul;11(3):188-94. PMID: 10414674
2. Effect of nonsteroid anti-inflammatory drugs on subarachnoid hemorrhage in dogs. White RP, Hagen AA, Robertson JT. J Neurosurg. 1979 Aug;51(2):164-71. PMID: 582181
3. Glisic E, gariner L, Josti L, et al. Inadequacy of Headache Management After Subarachnoid Hemorrhage. Am J Crit Care. 2016;25(2):136-143. Accessed at http://www.medscape.com/viewarticle/861069_5
4. Ravishankar K, Chakravarty A, Chowdhury D, et al. Guidelines on the diagnosis and the current management of headache and related disorders. Ann Indian Acad Neurol. 2011;14(Suppl1):S40-S59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152170/
5. http://vip.regionh.dk/VIP/Redaktoer/1301XC.nsf/vLookupUpload/ATTACH-RHAP-8X2FLV/$FILE/SAH%20Hemorrhage%20-%20A%20Guideline%20for%20Healthcare%20Professionals%20From%20the%20American%20Heart%20Association%20-%20American%20Stroke%20Association.pdf
6. Dhakal, L.P., Harriott, A.M., Capobianco, D.J., et al. Headache and Its Approach in Today’s NeuroIntensive Care Unit. Neurocritical Care. 2016; 25(2):320-334. (from SCOPUS)
7. Petzold, A., Girbes, A. Pain management in neurocritical care. Neurocrit Care. 2013; 19(2): 232-256 (from Scopus)
8. Friedman, B.W., Lipton, R.B. Headache emergencies: Diagnosis and management. Neurol Clinics. 2012; 30(1): 44-59
9. Dhakal LP, Hodge DO, Nagel J, et al. Safety and tolerability of gabapentin for aneurysmal subarachnoid hemorrhage (sah) headache and meningismus. Neurocrit Care. 2015;22:414–21.
10. Gottschalk A, Yaster M. The perioperative management of pain from intracranial surgery. Neurocrit Care. 2009;10:387–402.
11. Parkhutik V, Lago A, Tembl JI,et al. Influence of COX-inhibiting analgesics on the platelet function of patients with subarachnoid hemorrhage. J Stroke Cerebrovasc Dis. 2012 Nov;21(8):755-9. doi: 10.1016/j.jstrokecerebrovasdis.2011.04.002. Epub 2011 May 6. PMID 21550266
*Trip

Apr. 24, 2017Is there any evidence out there comparing IV to oral ketamine when it comes to efficacy for acute pain? details
 

Response: Overall, there is limited evidence for using oral Ketamine for acute pain. Of note, oral ketamine for acute pain is an off-label use. (1)
One limiting factor for the use of ketamine for acute pain may be the onset of action. While IV ketamine has an onset of action of 1-5 minutes, oral ketamine has an onset of 30 minutes. Oral bioavailability of ketamine ranges from 16-30% (and is highly variable due to extensive first pass hepatic metabolism). (2)
References: 1.CPS Monograph- ketamine
2. I.S. Grant, W.S. Nimmo, J.A. ClementsPharmacokinetics and analgesic effects of i.m. and oral ketamine. Brit J Anaesth 53 1981 805–810.
3. Robert A. Schoevers, Tharcila V. Chaves, Sonya M. Balukova, Marije aan het Rot, Rudie Kortekaas. The British Journal of Psychiatry Feb 2016, 208 (2) 108-113
4. Maren Blonk et al. Use of oral ketamine in chronic pain management: A review. European Journal of Pain. Volume 14, Issue 5; May 2010: 466–472.
5. J.R. Holtman Jr., P.A. Crooks, J.K. Johnson-Hardy, M. Hojomat, M. Kleven, E.P. Wala Effects of norketamine enantiomers in rodent models of persistent pain. Pharmacol Biochem Behav 90 2008676–685.
6. T. Rabben, P. Skjelbred, I. Oye Prolonged analgesic effect of ketamine, an N-methyl-d-aspartate receptor inhibitor, in patients with chronic pain.J Pharmacol Exp Ther 2891999 1060–1066.

Apr. 25, 2017What would be equivalent to Concerta 72mg per day? The patient cannot afford this. details
 

Patient Age: 29
Patient Sex: M
Medication History: Abilify 2mg
Cipralex
Response: 1. 72mg concerta is approximately equal to methylphenidate IR 40-60mg (1-5), with no established SR recommendation. Concerta 54mg is equivalent to methylphenidate SR 60mg daily (20-40 qam, then 20-40mg around 2pm). That would be a reasonable starting point, and another 20mg could be added QAM or QPM in 7 days if not satisfactory response (100mg max dosage CADDRA).

2. Biphentin could also be tried, but would cost similar to concerta at the dose required.
References: 1. Monographs
2. Lexi
3.PL Detail-Document, Comparison of ADHD Medications. Pharmacist’s Letter/Prescriber’s Letter. March 2016.
4. https://www.caddra.ca/pdfs/caddraGuidelines2011Chapter07.pdf
5. Handbook of Psychotropic Drugs, 20th edition

Apr. 25, 2017Bilaxten (Bilastine) is being dosed at 80mg once daily -- is there evidence to support such a high dose for urticaria? details
 

Patient Age: 31
Patient Sex: F
Medical Problems: Urticaria, continual
Response: 1. Only one study in humans with doses of 80mg could be found (1). This study (2) tested placebo, 20, 40, or 80mg doses in a crossover design for 7 days in cold-contact urticaria. Increasing efficacy found with increasing doses. No safety issues different than placebo. Could not find long-term studies for high doses like this.
References: 1. medline search, BILASTINE
2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3759706/
3. https://link.springer.com/article/10.1007%2Fs40261-016-0447-2

Apr. 26, 2017I want to give client azithromycin and he currently takes lamotrigine and has an allergy to sulfonamides. Is this a problem? details
 

Response: There are no interactions(1,2) and azithromycin is not related to sulfonamide antibiotics(3) so the client can safely receive the azithromycin.
References: 1. Stockley's
2. Lexicomp
3. Lexicomp - Sulfonamide Antibiotic Allergy

Apr. 26, 2017I have been getting lots of questions about Repatha and Praluent. Can these be used in patients that are intolerant to statins? The monographs indicate that they are adjuncts to maximum statin therapy. Is there a good resource other than the monographs to read more about the use of alternative therapies for LDL reduction? details
 

Response: Alirocumab (Praluent) and evolocumab (Repatha) may be used in patients with uncontrolled familial hypercholesterolemia or those with athersclerotic cardiovascular disease (primary hyperlipidemia).(7) It seems likely this drug would have application to a broad population of patients who don't tolerate other antihyperlipidemics, especially statins, and indeed these patients were included in trials.(3) However, the reliance of surrogate markers (LDL) for demonstration of effectiveness and lack of long-term safety data present obstacles to uptake.(2,3) The most significant obstacle is the price: these agents are >$600 per month acquisition cost.(7) The Common Drug Review (CDR) recommended against listing evolocumab for primary hyperlidemia.(5) While a recommendation was made in favour of alirocumab for primary hyperlipidemia, this was under the condition the price be reduced by 57%.(6) Currently neither drug is listed as a benefit for any indication so will only be used in patients who are willing to pay the out-of-pocket cost.(8)
It is thought that 90% of patients who report statin intolerance are able to continue statins after a step-by-step approach(9). The RxFiles has a great document of managing statin inolerance.(10)
References: 1. CTC - Dyslipidemias Ghislaine O. Roederer, MD, PhD Date of Revision: June 2016
2. https://www.cadth.ca/dv/pcsk9-inhibitor-monoclonal-antibodies-treatment-hypercholesterolemia
3. http://www.cjhp-online.ca/index.php/cjhp/article/viewFile/1580/2387
4. Sask formulary online
5. http://www.fhcanada.net/wp-content/uploads/2016/10/PCSK9_Repatha_Evolocumab_Common_Drug_Review.pdf
6. http://www.fhcanada.net/wp-content/uploads/2016/10/PCSK9_Praluent_Alirocumab_Common_Drug_Review.pdf
7. RxTx - eCPS - respective monographs
8. PharmaClik
9. http://www.acc.org/latest-in-cardiology/articles/2015/08/11/09/16/statin-intolerance-not-a-myth
10. http://www.rxfiles.ca/rxfiles/uploads/documents/Lipid-Statin-Intolerance.pdf

Apr. 26, 2017For the HbA1c blood test, could anything falsely change the results? details
 

Response: There are several potential factors that can affect HbA1c results; certainly anything that affects erythrocytes or hemoglobin can affect HbA1c.(1-7) Clinical significance in a general sense was not found. There are several case reports of unexplainable HbA1c results that the authors have traced to a particular interfering factor.(6) However, I suspect the clinical significance is very individual, possibly because of the spectrums of the severity of interfering conditions. The type of assay used can be a variable for some of the factors, but not all.(3,5,6) Most of the cases were identified because the HbA1c was inconsistent with daily blood glucose results; for instance, in one case the HbA1c of a patient on dapsone declined to 3.7% over several years despite the fact his blood glucose was uncontrolled.(8)

One article that is quite comprehensive.(7) It was published in 2009 though seemingly all that may have changed since then are the assays used. This article goes through all the different identified drugs and conditions that may affect HbA1c results, including iron deficiency and use of erythropoietin; it has a short paragraph on the complicated relationship between HbA1c and CKD.
It seems the only way to really know if something might be interfering with the assay is to compare assay results to the blood glucose levels. In patients whose HbA1c is not in line with their blood glucose levels, the only suggestions I found were to rely only on blood glucose levels or check fructosamine.(5) Fructosamine is available through the SK Disease Control Lab(9), though I don’t have any other information such as cost, proper application of the results, limitations of patient eligibility, etc.
References: 1. http://medsask.usask.ca/professional/Common-lab-tests-guide/index.php - Diabetes
2. http://guidelines.diabetes.ca/Browse/Chapter9#tbl1
3. https://www.aacc.org/~/media/practice-guidelines/diabetes-mellitus/diabetesmellitusentirelmpg.pdf?la=en
4. http://www.ngsp.org/interf.asp
5. HbA1c and monitoring glycaemia. Aust Fam Phys 2012; 41(1):37-40 http://www.racgp.org.au/afp/2012/januaryfebruary/hba1c-and-monitoring-glycaemia/
6. Unnikrishnan R, Anjana RM, Mohan V. Drugs affecting HbA1c levels. Indian J Endocrinol Metab. 2012;16(4):528-531. doi:10.4103/2230-8210.98004. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401751/#!po=30.0000
7. Gallagher E, Le Roith D, Bloomgarden Z. Review of hemoglobin A1c in the management of diabetes. J Diabetes. 2009;1(1):9-17
Possibly accessible via http://onlinelibrary.wiley.com/doi/10.1111/j.1753-0407.2009.00009.x/abstract
8. Kesson CM, Whitelaw JW, Ireland JT. Drug-induced haemolysis and fast haemoglobin A1 in diabetes mellitus. Br Med J. 1979;2:1037–8. (Case report referenced in [6])
9. http://sdcl-testviewer.ehealthsask.ca/Home/Details?id=365

Apr. 26, 2017I have a patient on warfarin going in for cataract surgery. Does she need to discontinue? The surgeon said it was up to me. details
 

Patient Age: 87
Patient Sex: F
Medical Problems: A fib, regular
HTN - controlled
asthma
CHAD2 S2-Vasc = 4; HAS-BLED = 2 (2)
Response: Cataract surgery carries a standard risk of bleeding.(1) While the patient's thromboembolic risk is high based on CHAD2S2-Vasc score, because the bleed risk is standard, no interruption in warfarin therapy is required.(1)
References: 1. http://medsask.usask.ca/documents/newsletters/33.2%20Periprocedural%20Antithrombotics.pdf
2. http://sparctool.com/

Apr. 26, 2017 I have a diabetic patient with asthma who has developed dry cough and worsening dypsnea post-MI. I suspect the ACE-inhibitor and beta blocker as potential causes. Is there any evidence for switching them? details
 

Patient Age: 65
Medical Problems: #Deleted
Medication History: #Deleted
Response: ARBs are proven to be effective options post-MI if ACE inhibitors are indicated but not tolerated. Valsartan (post-MI target 160 mg BID) from VALIANT trial and candesartan (32 mg daily post-MI target) from CHARM trial have evidence of being effective alternatives to ACE inhibitors post MI. (1,2,3,4,5) Note: The ramipril 10 mg daily dose that your patient is on was the post-MI target dose for ramipril.

Cardioselective beta blockers are preferred post-MI for those with asthma and DM (the cardioselective beta blocker acebutolol with intrinsic sympathomimetic activity less benefit). So we are left with metoprolol, bisoprolol, and atenolol as preferred options in these patients at cardioselective doses. (6,7) Metoprolol 100 mg BID is the target dose for post-MI. (8) 200 mg daily of metoprolol is also the maximum dose in which metoprolol can retain its cardioselectivity. (9) Therefore, the metoprolol 50 mg BID dose that your patient is on is a reasonable dose for a diabetic with asthma, and in fact he could potentially be titrated to the post-MI target dose of 100 mg BID if tolerated. (1)
References: 1. Jensen B, Reiger L. Post-Myocardial Infarction: Drug and Dosage considerations. RxFiles 11th edition. Updated March 2017.
2. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan in Acute Myocardial Infarction Trial Investigators (VALIANT). Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003 Nov 13;349(20):1893-906.
3. McMurray J, et al. The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). J Am Coll Cardiol. 2006 Feb 21;47(4):726-33.
4. Granger CB, McMurray JJ, Yusuf S, et al. CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet. 2003 Sep 6;362(9386):772-6.
5. McMurray JJ, Ostergren J, Swedberg K,et al.; CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003 Sep 6;362(9386):767-71.
6. O'Gara PT, Kushner FG, Ascheim DD et al. 2013 ACCF/AHA guideline for the management of st-elevation myocardial infarction. (STEMI) A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2012.
7. Which Beta-blocker. Med Lett 2001;43:9-11. & Drugs for Hypertension, Treatment Guidelines from the Medical Letter 2003; Vol 1 (Issue 6) 33-40.
8. Janosi A, Ghali JK, Herlitz J, et al.; MERIT-HF Study Group. Metoprolol CR/XL in postmyocardial infarction patients with chronic heart failure: experiences from MERIT-HF. Am Heart J. 2003 Oct;146(4):721-8.
9. Shelley R. Salpete. Cardioselective Beta Blocker Use in Patients With Asthma and Chronic Obstructive Pulmonary Disease: An Evidence-Based Approach to Standards of Care. Cardiovasc Rev Rep. 2003;24(11).

Apr. 27, 2017Is there established efficacy for Differin use in an 8 year old? details
 

Patient Age: 8
Patient Sex: M
Medical Problems: ?Acne?
Medication History: Adapalene
No other medications filled recently
Response: Assumption is that this is treating acne. Entry to market studies excluded children under the age of 12, so only post marketing data exists. Of this, the FDA has outlined ten's of serious adverse events, but no deaths attributable to adapalene. There is no evidence to suggest that it is safe to use in an 8 year old, but adapalene is poorly absorbed, and is also unlikely to cause a theoretical risk. Regardless, discuss side effects with the caregiver, and consider contacting the doctor for an alternate product if there are concerns surrounding the use of this product.
References: 1. UpToDate - Adapalene
2. FDA - Pediatric advisory committee - Adapalene

Apr. 27, 2017Is leflunomide truly contraindicated in chronic kidney disease patients? The monograph says it is, but there does not seem to be substatianting evidence for this. details
 

Patient Age: 83
Patient Sex: F
Medical Problems: 100 lb
GFR 26 (stage 4 CKD)
-rheumatoid arthritis
Medication History: Replavite B&C - 1 od
Metoprolol 50mg 1 bid
Vitamin D 2000IU once daily
Simvastatin 40mg 1 hs
Ramipril/HCTZ 10/12.5mg 1 od
Hydroxychloroquine 200mg 1.5 tabs once daily
Response: The very unsatisfying reason for the contraindication is insufficient study of leflunomide in CKD patients.(1-4) Like you, I struggle to understand the seemingly extreme precaution; certainly some inactive metabolites are excreted renally but the active metabolite is not excreted unchanged.(1) Two pieces of information lead me to believe a contraindication is unjustified:
1. Aubagio (teriflunomide = active metabolite of leflunomid[9]) has no contraindication nor dose adjustment requirement in CKD according to the monograph. In fact, the monograph states: “Severe renal impairment had no impact on the pharmacokinetics of teriflunomide. No dosage adjustment is necessary for patients with severe renal impairment.” (1) Considering leflunomide is essentially teriflunomide, it makes no sense that the two differ in terms of this recommendation.
2. The kinetics of leflunomide of five patients on hemodialysis were determined and found that removal of teriflunome was negligible (9). This patient is not on dialysis but this indicates to me patients with no renal function (either natural or renal replacement, since it did not remove the drug) are able to take leflunomide. It is important to mention this paper was strictly addressing the kinetics and made no mention of adverse effects or complications of using leflunomide in these patients. However, their data were collected between 2005 and 2010, which suggests to me they did not have problems with the drug in this population. Of course five patients is a small number.
Should the patient take the drug and experience severe adverse effects, one could also consider the availability of activated charcoal/cholestyramine for enhanced removal of leflunomide reassuring.
Considering the high protein binding of leflunomide (99.3%), it would be prudent to ensure the patient has adequate serum albumin levels.
References: 1. eCPS - respective monographs
2. Renal Drug Handbook 2010
3. AHFS
4. https://www.medicines.org.uk/emc/medicine/24155
5. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000235/WC500026289.pdf
6. http://www.medsafe.govt.nz/profs/Datasheet/a/aravatab.pdf
7. https://arthritis-research.biomedcentral.com/articles/10.1186/ar3256
8. Swarup A, Sachdeva N, Schumacher HR: Dosing of antirheumatic drugs in renal disease and dialysis. J Clin Rheumatol. 2004, 10: 190-204. PMID 17043508
9. Clin Rheumatol. 2013 Feb;32(2):267-70. doi: 10.1007/s10067-012-2122-1. Epub 2012 Nov 22. Leflunomide in dialysis patients with rheumatoid arthritis--a pharmacokinetic study.
Bergner R1, Peters L, Schmitt V, et al. PMID: 23179005

Apr. 28, 2017Can you comment about this red box / blue box "Xyngular" product? details
 

Response: I can’t provide you with a complete review of this product. The main reason is the way the manufacturer lists the ingredients, it is impossible to know the dosages of any one ingredient; secondly, there are just so many ingredients it would take a week and I know my response will be the same: there is no evidence to support claims; one cannot be sure the product contains what is listed (and more importantly does not contain undeclared ingredients such as stimulants).

As for the dosages, all of the products are listed as ‘proprietary blends’. As an example, it would be like taking a combination cold and flu product and listing like this:
ColdBeGone proprietary blend 3850 mg
acetaminophen, brompheniramine, dextromethorphan, guaifenesin
Clearly that’s not very helpful!

There are a lot of sources of caffeine in the product (denoted with an asterisk in the ingredients below) which is typical for weight loss products. Because we don’t know the amount of each individual ingredient, it is impossible to know how much caffeine would be consumed over the course of a day. One of the products also contains bitter orange, which has stimulant properties, which again, if the dose is unknown, can be potentially dangerous. Also, typical of weight loss products are laxatives, which are found in Flush. So people lose water weight and feel good about themselves.

This is what is in the blue box:

New Global Blend
We recommend taking 1-2 ounces of Global Blend at your convenience without food.
Proprietary Hi Orac Blend 6400 mg
several fruits and extracts, green tea extract*, sea buckthorn, grape seed extract, raspberry seed extract, white leaf tea*, aloe vera juice concentrate (from 1 mg 200:1 concentrate), goji berry, noni fruit, mangosteen
Proprietary Adaptagen Blend 50 mg
Amia fruit, panax ginseng root extract, eleuthero root
Proprietary Primary 30 mg
antioxidant complex - l-glutamic acid, l-cysteine, glycine

Accelerate
We recommend taking 2 accelerate mid-afternoon with food
Propietary Blend 850 mg
Green tea leaf*, guarana seed extract*, oolong tea extract*, kola nut extract*, cayenne pepper

Axion
We recommend taking 2 Axion first thing in the morning with food.
vitamins/minerals,
inositol 12.5 mg, lycopene 2 mg, lutein 5 mg, ALA 12.5 mg, quercetin 25 mg, CoQ10 12.5 mg, flaxseed 50 mg, bromelain 25 mg, papain 12.5 mg, pepsin 12.5 mg, spirulina 50 mg, resveratrol 5 mg, green tea leaf extract* 30 mg, rhodiola root extract 10 mg, panax ginseng root extract 10 mg, probiotics

Cheat+
We recommend taking Cheat+ 30 minutes before a meal. Always consume a minimum of 8oz of water when taking Cheat+.
Proprietary Blend 1230 mg
glucomannan, green coffee bean extract*, phytosterols, hydroxypropyl cellulose

Flush
We recommend consuming 2 flush before sleep on an as empty stomach
Proprietary blend 1300 mg
senna leaf powder, cinnamon bark, psyllium husk powder, fenugreek, clove, garlic bulb, aloe vera, ginger root, dandelion, slippery elm bark

Lean
We recommend consuming 1 scoop of lean with your choice of beverage, as outlined in the program you are utilizing.
More vits/minerals/fruit extracts/enzymes
Amino acid proprietary blend
alanine, arginine, aspartic acid, cystine, glutamic acid, glycine, histidine, isoleucine, lysine, methionine, phenyllalanine, proline, serine, threonine, taurine, tryptophan, tyrosine, valine
Lean Propietary bledn 13.4 g
soy isolates, soy milk, whey isolates, whey concentrates

Spryng
We recommend consuming Spryng on an empty stomach before or during exercise or another challenging event that requires mental and physical energy. (= energy/sports drink)
some vitamins
Proprietary blend 7, 138 mg
palatinose, l-citrulline, l-glutamine, ElevATP ancient peat and apple extract, ashwaganda root, alpha GPC, CoQ10, lycium berry 10:1 extract, cordyceps

Xyng
We recommend consuming 1 capsule of Xyng with food, no later than 3pm. If Xyng is well tolerated then it can be consumed on an empty stomach.
Proprietary Blend 733 mg
caffeine anhydrous*, white willow bark, 5-HTP, bitter orange extract, 30% synephrine alkaloids, garcinia cambogia - 60% hydroxycitric acid, green tea leaf extract*, cayenne pepper, rhodiola, korean ginseng root, maca root, black tea leaf extract*, yohimbe, undaria, black pepper

XR2
We recommend consuming 2 tablets on an empty stomach as needed to combat stress, stress eating, and improve sleep.
Proprietary Blend 670 mg
magnolia bark, phellodendron, valerian root, l-theanine, GABA, 5-HTP, celery seed

Xypstix
We recommend using 1 stick at your convenience without food.
Proprietary blend 550 mg
fruit extracts, acai fruit, goji berry, noni fruit, green tea leaf*, seabuckthorn fruit extract, white tea leaf*
Proprietary antioxidant blend 10 mg
l-glutamic acid, l-cystine, glycine, melon extract
Proprietary adaptagen blend 2000 mg
aloe vera juice, amla fruit extract, panax ginseng root, eleuthero root
References: 1. http://www.xyngular.com/en/products/faq-xypstix/
2. Natural medicines

May. 2, 2017Is Cevimeline available in Canada? details
 

Response: Cevimeline (Evoxac) is not available in Canada through the usual routes (1-3), nor the Special Access Programme (6), despite the fact Lexicomp lists it avaialble in Canada.(4) It is a muscarinic agonist that may last slightly longer and may be better tolerated than pilocarpine. Cevimeline may have a lower risk of bradycardia and bronchospasm than pilocarpine due to greater selectivity for the type of muscarinic receptors found in the mouth. Approved for dry mouth due to Sjögren’s syndrome, as is pilocarpine. (5)
References: 1. DPD
2. NOC database
3. drugbank.ca
4. Lexicomp
5. Canadian Pharmacist's Letter 2010; 26(10):261006
6. Phone communication SAP, 613-941-2108, May 3, 2017

May. 3, 2017For a patient who is over 80 years old and weighs less than 60kg, what is the dose for apixaban? details
 

Response: For non-valvular atrial fibrillation, a patient 80+ years and weighing <=60 kg should receive a dose of 2.5 mg twice daily.(1-3)
References: 1. Sk Formulary EDS Criteria
2. eCPS
3. http://www.rxfiles.ca/rxfiles/uploads/documents/CLOT-Apixiban-Checklist-Final-CPP.pdf

May. 3, 2017Can dexamethasone IV be given orally to a baby? details
 

Medical Problems: sodium phosphate
Response: Oral administration of the parenteral dexamethasone products to children has been evaluated and deemed acceptable.(3) The parenteral products are dexamethasone sodium phosphate but are labelled as amount of dexamethasone phosphate.(2) The molecular weight of dexamethasone phosphate is 472 g/mol and that of dexamethasone is 392 g/mol.(1) Therefore, each mg dexamethasone phosphate delivers 0.83 dexamethasone base.
References: 1. Martindale's
2. PMs from DPD
3. http://www.medscape.com/viewarticle/758927#vp_2

May. 3, 2017What would be the equivalent liquid dosage of phosphate compared to the 500mg sodium phosphate effervescent tablets? details
 

Response: The tablets contain phosporus 500 mg = 16 mmol.(1) As the liquid contains 20.7 mmol phosporus per 5 ml(2), an equivalent dose would be 3.86 ml.
References: 1. eCPS - Phosphate Novartis monograph
2. http://medsask.usask.ca/documents/drug-shortages/Sodium%20Phosphate.pdf

May. 3, 2017Can my patient still use the Twinrix that was left at room temperature for a day? details
 

Response: Off-label information indicates stable for 72 hours at temperatures between 8°C to 25°C but it is still recommended to contact the manufacturer with lot number and details. (1)
References: 1. Canadian Pharmacist's Letter 2008; 24(10):241014

May. 4, 2017Is there anywhere someone can find out interactions with cannabis oil? In this particular case the drug is azithromycin. details
 

Response: Both Stockley's and lexicomp include cannabis and do not list any interactions with azithromycin.(1,2) Drug cocktails suggests 'unknown danger'.(3)
References: 1. Stockley's
2. Lexicomp
3. http://drugcocktails.ca/medications/azithromycin

May. 4, 2017How is H.pylori treated in pediatrics? details
 

Medical Problems: 23kg child
Response: The regimens used in adults is what should be used for pediatrics at pediatric doses.(1) Quadruple therapy is now recommended as first line(1,2) and since tetracycline should not be used in young children(2), this leaves PPI + amoxicillin + metronidazole + clarithromycin.(1,2) Doses are all divided BID(3):
omeprazole 1-2 mg/kg/d or fixed dose in this child would be 10 mg BID
amoxicillin 50 mg/kg/d
metronidazole 20 mg/kg/d
clarithromycin 20 mg/kg/d
References: 1. Bugs and Drugs App
2. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Hpylori.pdf
3. Lexicomp

May. 5, 2017Distilled water is not available - is demineralized water the same? details
 

Response: Yes.
Purified water is prepared by distillation, ion-exchange (deionization, demineralization) reverse osmosis, or other methods.(2) Because none of the cited uses of Distilled Water imply a need for a particular purity attribute that can only be derived by distillation, water meeting the requirements of Purified water derived by other means of purfication could be equally suitable whenever Distilled Water is specified.(3)
References: 1. AHS Compounding Manual
2. Remingtons
3. https://hmc.usp.org/sites/default/files/documents/HMC/GCs-Pdfs/c1231.pdf
*USP, PL

May. 5, 2017How is Bordetella holmesii treated? details
 

Response: Boretella holmesii has only recently be recognized as a pathogen and much is unknown about it, including transmission, clinical manifestations, need for antibacterial therapy, and if so, which antibacterial therapy.(2-6) To date, the only information regarding antibiotic therapy comes from in vitro susceptibility tests in which it is most susceptible to fluoroquinolones (specifically ciprofloxacin and levofloxacin) and carbapenems, but not to third-generation cephalosporins or, surprisingly, erythromycin. Clarithromycin and azithromycin were not tested.(4) While co-trimoxazole was found to have a low MIC(4), resistance has been reported elsewhere.(5,6)
References: 1. UTD - Pertussis infection: Epidemiology, microbiology, and pathogenesis
2. Clin Infect Dis. 2014 Jan;58(2):e39-43. doi: 10.1093/cid/cit669. Epub 2013 Oct 2. Bordetella holmesii bacteremia cases in the United States, April 2010-January 2011. Tartof SY1, Gounder P, Weiss D, et al. PMID 24092805
3. http://www.globalrph.com/bugs2.htm
4. https://academic.oup.com/cid/article/38/6/799/319520/Bordetella-holmesii-Bacteremia-A-Newly-Recognized
5. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099(14)70021-0/fulltext
6. http://www.tandfonline.com/doi/full/10.1586/14787210.2015.1056161?scroll=top&needAccess=true

May. 5, 2017What is the difference between prednisone and prednisolone? details
 

Response: Prednisolone is the active metabolite of prednisone; dosing is the same for the two.
References: 1. eCPS - Corticosteroids: Systemic

May. 5, 2017We recevied a hospital discharge for Bacid ii BID. Is there anything similar? details
 

Response: Culturelle contains 10 or 20 billion CFU per capsule of the GG strain(2) whereas Bacid contains 1 billion of the strain HA-111.(1) However, the research has been undertaken with the Culturelle strain.(3)
References: 1. http://eci2012.net/product/bacid/
2. https://www.culturelle.com/products/digestive-health-probiotic-capsules
3. Natural Medicines
4. http://www.probioticchart.ca/

May. 7, 2017Can Transderm-V be placed other than behind the ear? details
 

Response: One study regarding absorption of scopolamine from transdermal patches placed at sites other than postauricular has been published.(1) As one would expect, absorption was lower at other sites tested; specifically, the back and chest were half as permeable whereas the thigh was 10-20 times less permeable than the postauricular site. Of the sites tested, the back was the most permeable. Reduced absorption should be expected if the location is changed.
References: 1. (OVID): Nachum Z. Shupak A. Gordon CR. Transdermal scopolamine for prevention of motion sickness : clinical pharmacokinetics and therapeutic applicationsClinical Pharmacokinetics. 45(6):543-66, 2006.

May. 8, 2017How is hydromorphone converted to methadone? details
 

Patient Age: 41
Patient Sex: F
Medication History: Hydromorph contin 30mg tid
Hydromorph IR 4mg qid
many other medications as well
Response: The patient takes 106 mg hydromorphone daily, which is equivalent to 530 mg morphine (1,4). Different equivalency tables have different values for conversion to methadone. At a daily morphine dose of 530 mg these range from 1:10 (53 mg methadone)(2,4), 1:15 (35 mg methadone)(3,5). These tables apparently take into account cross-tolerance though some still prefer to further reduce for incomplete cross-tolerance.(3) As such, 30 mg daily methadone seems like a reasonable start, though preferably divided into three doses (10 mg TID).(3,4)
References: 1. http://nationalpaincentre.mcmaster.ca/opioidmanager/documents/opioid_manager_switching_opioids.pdf
2. cps
3. https://www.pbm.va.gov/PBM/clinicalguidance/clinicalrecommendations/Methadone_Dosing_Recommendations_for_the_Treatment_of_Chronic_Pain_July_2016.pdf
https://www.cpsbc.ca/files/pdf/Methadone-Program-Recommendations-for-the-Use-of-Methadone-for-Pain-PUBLIC.pdf
4. https://www.cpsbc.ca/files/pdf/Methadone-Program-Recommendations-for-the-Use-of-Methadone-for-Pain-PUBLIC.pdf

May. 8, 2017How should a general dental infection (acute simple gingivitis) be treated in someone allergic to penicillins, clindamycin and erythromycin? details
 

Patient Age: 35
Patient Sex: F
Response: 1. Penicillins (including amox / amp) and clindamycin are the first-line treatments in dental infections (1,2). The second line options include (1-3):
- Macrolides: Cover most of the typical dental pathogens, except anaerobes, though increasing resistance. Ex. Azith 500mg day 1, 250mg day 2-5 (3).
- Tetracyclines: Increasing resistance to the gram-negative and anaerobic activity of tetracyclines, but can be used. Ex. Doxycycline 100mg BID x 7-10d (3)
- Metronidazole (500mg q12h): Should be added to above regimens if anaerobic pathogens suspected, typically in more severe or deep infections.
References: 1. https://www.cda-adc.ca/jcda/vol-64/issue-7/antimicrobial-t-pic1.html
2. http://www.jcda.ca/article/a37
3. http://www.medscape.org/viewarticle/449821_7
*UpToDate, Management of periodontal disease

May. 9, 2017How do I find the alternatives to Buscopan? details
 

Response: http://medsask.usask.ca/documents/drug-shortages/Hyoscine%20butylbromide.pdf

May. 9, 2017Would an anaphylactic acetylsalicylic acid (ASA) allergy cause cross-reactivity to topical diclofenac? details
 

Response: There are two types of NSAID reactions: pseudoallergic and IgE-mediated.(1,2,4) Most reactions to ASA are pseudoallergic(1), which is a function of COX-1 inhibition.(1,2,4) For those with IgE-mediated reactions, other NSAIDs do not need to be avoided.(1,2,4) Those with severe pseudoreactions should avoid all NSAIDs to be prudent.(1,2) One needs to keep in mind the following:
- considering the pseudoallergy is due to COX-1 inhibition, it is suggested to use COX-2 selective agents as alternatives.(1,2,4) While diclofenac is not ever mentioned as one of these (1,2,4), it is COX-2 selective.(3)
- the reaction would seem to be dose-dependent: when undertaking ASA desensitzation, the first dose is oral and between 20-80 mg.(2)
- Systemic absorption of Emulgel is ~ 6%(5) based on application of 2.5g. If 2.5 g is applied of 8%, 200 mg diclofenac is applied and if 6% is absorbed = 12 mg reaching systemic circulation. The oral bioavailability of diclofenac is 55%(6) so someone taking a 50 mg tablet would have 27.5 mg in circulation. Because this isn't a huge difference, it would be prudent to start with Emulgel because of its signficantly lower concentration.
References: 1. UTD - NSAIDs (including aspirin): Allergic and pseudoallergic reactions
2. Lexicomp - Salicylate Allergy/Sensitivity (Drug Allergy and Idiosyncratic Reactions)
3. Canadian Pharmacist's Letter 2017; 33(1):330127
4. Canadian Pharmacist's Letter 2010; 26(10):261011
5. eCPS - Emulgel
6. Lexicomp

May. 9, 2017We have a question about comparing Dilantin Infatabs compared to the Suspension. We have a patient who came in on suspension but all we have are the infatabs. Do we give the same dose? details
 

Response: No dose adjustment is needed when switching between the suspension and Infatabs(1,2); slight adjustment may be required when switching to or from Dilantin capsules.(1)
References: 1. http://medsask.usask.ca/documents/drug-shortages/Phenytoin.pdf
2. eCPS - Dilantin Infatabs

May. 9, 2017Can pentasa tablets be split? details
 

Medical Problems: Crohn's
Medication History: Pentasa
Response: Pentasa tablets are composed of extended release microgranules that allow for continuous release of drug throughout the small and large intestines; the extended release nature of the granules allows for topical (local) distribution to the intestines. When 5-ASA is not formulated in an extended release formulation, 80% of the drug is absorbed systemically compared to 20-30% when it is in extended release form. Therefore, if a tablet is split, some of the microgranules will be split thereby comprimising the coating and promoting systemic absorption, which could result in less symptom control. If the patient finds her symptoms are not controlled or needs to be increasing the dose, it could be because the tablets are being split.(1)
References: 1. eCPS

May. 9, 2017How should the ISMN shortage be handled? details
 

Response: Referred to http://medsask.usask.ca/documents/drug-shortages/Isosorbide%20Dinitrate.pdf
and sent:
- ISDN 20mg TID, last dose 7pm, may need to tirate up
- Possibly slightly less effective than ISMN (likely due to tolerance / compliance issues)
- More headache

Bottom line: Therefore, while it seems that isosorbide-5-monohydrate has benefits over the shorter acting isosorbide dinitrate, isosorbide-5-dinitrate is still effective for the relief of angina and improved exercise tolerance, and would be an acceptable alternative in the wake of a monohydrate shortage. 20 mg TID of the dinitrate formulation can be used instead of the 60 mg monohydrate formulation. Make sure the last tablet is given at 7pm to ensure a drug free interval.

After reviewing the abstracts of 4 trials, the following can be concluded about the comparative efficacy between isosorbide dinitrate and isosorbide-5-mononitrate:

o The use of both isosorbide dinitrate and 5-mononitrate was associated with significant improvements of exercise tolerance however effect of mononitrate lasted longer (1) (Time to onset of chest pain was significantly increased by both drugs; Isosorbide-5-mononitrate increased total exercise time, both after a single dose and after 2 weeks’ therapy; Time to onset of chest pain was significantly increased by both drugs; Isosorbide-5-mononitrate increased total exercise time, both after a single dose and after 2 weeks’ therapy; Total exercise time was significantly increased only after 2 weeks’ therapy with isosorbide dinitrate (p<0.05); An increase in total exercise time of 230 seconds was experienced by 18 of 23 patients (78%) receiving isosorbide--mononitrate for 2 weeks and by 16 of 23 (70%) receiving isosorbide dinitrate. (5))

o Tolerance is more likely to develop with isosorbide dinitrate than with isosorbide mononitrate (i.e. dose of dinitrate had to be increased throughout trial, whereas the dose for mononitrate did not (2); effect of dinitrate had diminished after 1 week of sustained qid therapy with isosorbide dinitrate (3), the effective dose of mono mac was 1.5-2 times less than that of nitrosorbide or cardiket, thus it is more cost-effective (4); )

o Greater risk for experiencing headache adverse effect with dinitrate vs monohydrate (Number of attacks of headache increased during first week of treatment with both drugs, became even higher by the end of use of dinitrate and decreased by the end of use of mononitrate (2), Headache was the only clinically significant adverse experience, and was reported by 10 of 28 patients during treatment with isosorbide-5-mononitrate (not significant compared with placebo; 1 severe, 3 moderate and 6 mild) and 15 of 28 patients during treatment with isosorbide dinitrate (p <0.05 compared with placebo, not significant compared with isosorbide 5-mononitrate; 1 severe, 10 moderate and 4 mild) (5)).

Therefore, while it seems that isosorbide-5-monohydrate has benefits over the shorter acting isosorbide dinitrate, isosorbide-5-dihydrate is still effective for the relief of angina and improved exercise tolerance, and would be an acceptable alternative in the wake of a monohydrate shortage.

Other differences:
- ISDN onset in 30 min, ISMN ~4hr. ISDN duration 5h, ISM 12h.
- Should use ISDN oral swallow tablets, not SL form for angina prophylaxis.
- http://www.unc.edu/~vreddy/index_files/Medical%20Resources/Pharmacy/formularyequivguide.pdf --> 30mg OD ISMN = 40mg daily ISDN
- (6), ISDN 40mg BID was equivalent to ISMN 20mg BID
- (7), 80mg ISDN reduced to 45mg ISMN
- (8,9), heart failure studies compared same doses of ISMN and ISDN; each had same effect, but ISDN would wear out sooner.
References: (1) CPS – Nitrates
(2) Martsevich SIu, Semenova IuE, Alimova EV, Dmitrieva nA, Kozyreva MP, Koniakhina IP, Lukina IuV, Egorov VA. [Selection of therapy with nitrates in patients with stable effort angina: results of comparative study of common isosorbide dinitrate and long acting preparation of isosorbide-5-mononitrate]. Kardiologiia. 2005;45(11):42-5.
(3) Parker JO Controlled release isosorbide-5-mononitrate in angina pectoris: a comparison with standard formulation isosorbide dinitrate. Can J Cardiol. 1991 Apr;7(3):125-30.
(4) Lupanov VP, Alekseeva IA, Vasil'eva NN, Chotchaev KhKh, Naumov VG. [Comparative study of isosorbide dinitrates and mononitrates in patients with ischemic heart disease and stable angina pectoris caused by stenosing coronary atherosclerosis]. Klin Med (Mosk). 2000;78(9):52-5.
(5) Seabra-Gomes R1, Aleixo AM, Adao M, Machado FP, Mendes M, Bruges G, Palos JL. Comparison of the effects of a controlled-release formulation of isosorbide-5-mononitrate and conventional isosorbide dinitrate on exercise performance in men with stable angina pectoris. Am J Cardiol. 1990 Jun 1;65(20):1308-12.
6. Bidoggia H: Isosorbide-5-mononitrate and isosorbide dinitrate retard in the treatment of coronary heart disease: a multi-centre study. Curr Med Res Opin 1987; 10:601-611.
7. Micromedex comparative efficacy
8. Rabinowitz B, Hod H, Chouraqui P, et al: Hemodynamic effects of oral isosorbide-5-mononitrate and dinitrate in ischemic heart failure. Clin Cardiol 1987; 10:603-608.
9. euhaus R, Johnen R, Vydra L, et al: Comparative clinical trial of isosorbide 5-mononitrate and sustained-release isosorbide dinitrate in ischaemic heart disease. Pharmatherapeutica 1986; 4:486-495.

May. 10, 2017Is Narcan available as nasal spray in Canada? details
 

Response: Health Canada has approved Narcan nasal spray (2) though it is not available through wholesalers at this this time and there is no projected timeline (though in the fall of 2016, the projected timeline was Spring 2017[1]).(3) Pharmacies can order direct from Adapt Pharma after creating an account(3); this is possible because of an Interim Order of the Minister of Health from July 2016.(1)
References: 1. Previous research for Opioid toxicity lectures; Nov, 2016; in lecture slides
2. DPD
3. Phone communication with Adapt pharma 1-877-870-2726, May 11 2017

May. 10, 2017How should a patient switch between gabapentin and pregablin? details
 

Patient Age: 71
Patient Sex: M
Medication History: gabapentin 300 mg TID
pregabalin 75 mg BID
Response: Equi-Analgesic dose gabapentin to pregabalin is considered approx 6:1. (3) Small studies have shown tolerance for a straight switch (2), ie, taking usual gabapentin hs dose and starting the next morning with the Lyrica, Since he is taking 900 mg gabapentin, Lyrica 75 mg bid is a reasonable dose; monitor for adverse effects. (3) Another option would be to decrease the gabapentin dose by 50% and add 50% of the Lyrica dose for 4 days then switch to the full Lyrica dose. Both were well tolerated. (1)
References: 1. Bockbrader HN1, Budhwani MN, Wesche DL. Gabapentin to pregabalin therapy transition: a pharmacokinetic simulation. Am J Ther. 2013 Jan;20(1):32-6. PMID 23018586
2. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010;11(3):456-65.
3. http://www.pharmacytimes.com/contributor/jeffrey-fudin/2015/09/how-gabapentin-differs-from-pregabalin

May. 10, 2017I would like to treat a client with azithromycin and ceftriaxone. He is on Seroquel. Any interactions? details
 

Patient Age: 28
Patient Sex: M
Medical Problems: no other medical issues
Medication History: Seroquel 25 mg PO BID PRN
Response: The only potential risks is QT prolongation between Seroquel and azithromycin.(1-3) However, this client has no other risk factors (1,4) so the combination is not a concern.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-QA%20TORSADESdePoint.pdf
2. Lexicomp
3. Stockley's
4. QT prolonging drugs: assessement and management of risk in Jade/DzFiles/3. Cardiovascular/QT

May. 10, 2017How long should one wait between doses of epinephrine for anaphylaxis? details
 

Response: Doses can be repeated every 5-15 minutes as needed. (1,2)
References: 1. http://s3.amazonaws.com/files.cps.ca/document/526/print-ready_e.pdf?AWSAccessKeyId=AKIAIQDIKLPWFMPMSEAA&Expires=2145934800&Signature=jQ9JnSRwQTE690jXDUw7XlJXJKY%3D
2. eCPS - Epipen

May. 10, 2017Fenofibrate micro 200 mg is shorted. What would be the most similar agent? details
 

Response: Fenofibrate micro 200 mg = 145 mg nanocrystal tablet (Lipidil EZ) or 160 mg micronized tablet (Lipidil Supra).(1,2) Only the EZ formulation is on the SK Drug Plan.
References: 1. eCPS - CPhA Fibrates monograph
2. http://medsask.usask.ca/professional/drug-shortages/index.php

May. 10, 2017What is the process for obtaining medical marijuana legally? details
 

Response: Forms for Health Canada need to be submitted by prescribing physicians. (1) Cannimed, a supplier in SK has forms on their website.(2) It is unclear if these forms replace those required by Health Canada or if these are to be submitted after approval by Health Canada. Caller to contact Cannimed.
References: 1. http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/faq-eng.php
2. https://www.cannimed.ca/pages/prescription-forms

May. 10, 2017How significant is the interaction between cotrimoxazole and perindopril? Is it dose-dependent? details
 

Patient Age: 55
Patient Sex: F
Medical Problems: eGFR Apr 24 2017: 93 ml/min
Infection unknown
K+ in Jan 2017: 3.8 mEq/L
Medication History: Cotrimox daily x 2months
perindopril 4 mg daily
Response: It seems that the interaction would be dose-dependent as the interaction is additive.(2) There is evidence that the interaction is more severe in patients taking high versus low dose trimethroprim(1); however, in this case, high dose refers to doses >5 mg/kg/day used for HIV and low dose would encompass both the single-strength and double-strengths of co-trimoxoxazole. There is no direct evidence risk is lower when using single strength versus double strength. If the patient is >65 years, co-trimoxazole should probably be avoided considering she's on perindopril.(2) Potassium needs to be checked on day 4 or 5.(1) Considering there is no direct evidence of a signficant difference in interaction between single-strength and double-strength, if double-strength is indicated for the infection, it should be used. MD is aware of interaction and plans to check potassium weekly (suggested day 4-5 for the first one).
References: 1. Canadian Pharmacist's Letter 2015; 22(1):310102
2. Stockley's

May. 12, 2017Can pilocarpine eye drops be administered orally for dry mouth? What dosage is appropriate? details
 

Patient Age: 63
Patient Sex: F
Response: Pilocarpine — A systematic review of the literature identified nine randomized trials that studied pilocarpine in the postradiation setting. The review concluded that approximately 50 percent of patients with xerostomia benefit from oral pilocarpine following RT. Continuous treatment with doses greater than 2.5 mg three times per day is required for optimal response, with some patients needing up to 12 weeks to experience benefit. Typical pilocarpine dose for xerostomia is 5–10 mg TID po. Lifelong therapy is required. (2)
Pilocarpine causes frequent side effects. These include sweating, headaches, tachycardia, hypertension, flushing, and increased bowel and bladder motility. Pilocarpine should be avoided in patients with uncontrolled asthma, acute angle glaucoma, or known hypersensitivity to pilocarpine. (3)
Tablets are expensive(1) so:
Dosage of pilocarpine eye drops (from 2015-2016 database ID 1931)
- The drops are available as 1%, 2%, and 4%(9) providing 0.5 mg, 1 mg, and 2 mg per drop, respectively.
- Some physicians are having patients take 4 to 5 drops (0.25 mL) of 2% pilocarpine ophthalmic solution in 4 ounces of water QID.
- Opthalmic pilicaropine 4%: Sig: 2 drops on the tongue and swallow QID daily (2 mg/drop)
References: 1. Canadian Pharmacist's Letter 2015; 22(2):310208
2. Jensen et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: management strategies and economic impact. Support Care Cancer. 2010;18(8):1061.
3. Jham et al. A randomized phase III prospective trial of bethanechol to prevent radiotherapy-induced salivary gland damage in patients with head and neck cancer. Oral Oncol. 2007 Feb;43(2):137-42. Epub 2006 Jun 23.

May. 12, 2017Does Sanis doxycycline (capsules [DIN 02351234 ] or tablets [DIN 0235124]) contain gluten? details
 

Response: No, neither the Sanis doxycycline capsules nor tablets have ingredients that are sources of gluten.(2)
References: 1. Jade/Dz Files/24. General Files/Excipients/Gluten Cheat Sheet
2. Phone communication with Sanis medical information, 1-866-236-4076

May. 15, 2017Regarding Estrosense by Womens Sense, what are these two ingredients: sulforaphane and indole-3-carbinol. Is there any safety information on these? details
 

Patient Age: 39
Patient Sex: F
Medication History: not available
Response: Sulforaphane and indole-3-carbinol are essentially the broccoli in the supplement; both of these are molecules derived from broccoli.(1,2) Unfortunately, Natural Medicines suggests there is insufficient information available for safety and effectiveness of sulforaphane; it was not listed in any of the other references I consulted. There is marginally more information regarding indole-3-carbinol in that it is considered possibly safe at doses of 200-400 mg daily for up to 3 months or 100-200 mg daily for up to 15 months.(1) Adverse effects include skin rash and small increases in ALT; in doses > 400 mg, it may cause disequilibrium syndrome, nausea, and tremor.(1,3) There is some in vitro data suggesting both compounds may induce CYP1A2.(1)
References:
1. Ulbricht K, Basch E, editors. Online Natural Medicines[Internet]. Somerville (MA); c2017 [cited 16 May 2017]. Available from: https://naturalmedicines.therapeuticresearch.com/ Subscription required.
2. Houghton CA, Fassett RG, Coombes JS. Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality? Oxid Med Cell Longev. 2016;2016:7857186.
3. Indole-3-carbinol. In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: 16 May 2017).

May. 15, 2017Can ciprodex be used in the eye? details
 

Response: While eye drops can genearlly be used in the ear, ear drops should not be used in the eye because they may not be isotonic, appropriate pH, or preserved.(1,2) Corticosteroids generally should be avoided for conjunctivitis.(3)
References: 1. Canadian Pharmacist's Letter; October 2006; Vol: 22
2. Pharmacist's Letter - The Ins and Outs of Eye and Ear Meds
3. medSask Conjunctivitis Guideline in development - http://medsask.usask.ca/professional/guidelines-in-development/conjunctivitis-bacterial,-viral-and-allergic.php

May. 15, 2017Could you by chance assist in enlightening us on the smoking of fentanyl patches? details
 

Response: I started by going to erowid.org to find out what techniques are used. Unfortunately, all of the posts were from the early 2000s when the fentanyl patches were reservoir and the gel could be extracted then heated. Now, it seems they just heat the entire piece of patch (the patch is cut into the ‘correct dose’) on some tinfoil and use a tubular/cylindrical object to inhale the fumes.(1) I suspect there have been more sophisticated techniques developed as well.

As for published journals, I only found an analysis of heated fentanyl and a few case reports.
I was hoping the analysis of the heated fentanyl would provide some insight into possible harmful substances formed by combustion of the patch materials; however, it only reported on the metabolites of fentanyl from heated fentanyl HCl powder and that of heated fentanyl citrate extracted from a Duragesic reservoir patch (which even if products of combustion were reported it wouldn’t necessarily be applicable to the matrix patch).(2)

Beyond this, I only saw three case reports. One case reported alveolar proteinosis as a result of smoked fentanyl patches; for some reason, this study is not available to me so I only had the limited information from the abstract.(3) As this was published in 2012 it is hard to predict if the product used would have been reservoir or matrix. The other two case reports simply report on overdoses in which contents of reservoir fentanyl patches had been smoked.(4,5)
References: . https://drugs-forum.com/threads/how-to-smoke-fentanyl-patches-safely-non-gel-type.148708/
2. Nishikawa RK, Bell SC, Kraner JC, et al. Potential biomarkers of smoked fentanyl utilizing pyrolysis gas chromatography-mass spectrometry. J Anal Toxicol. 2009 Oct;33(8):418-22.
3. Chapman E, Leipsic J, Satkunam N, et al. Pulmonary alveolar proteinosis as a reaction to fentanyl patch smoke. Chest. 2012 May;141(5):1321-1323.
4. Martin T, Woodall K, McLellan B. Fentanyl-related deaths in Ontario, Canada: Toxicological findings and circumstances of death in 112 cases (2002-2004). J Analyt Toxicol 2006; 30(8):603-610.
5. Marquardt K, Tharatt S. Inhalation abuse of fentanyl patch. Clin Toxicol 1994; 32(1): 75-78. Abstract only

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1. Potential biomarkers of smoked fentanyl utilizing pyrolysis gas chromatography-mass spectrometry. Nishikawa RK, Bell SC, Kraner JC, Callery PS. J Anal Toxicol. 2009 Oct;33(8):418-22. PMID: 19874647
2. https://www.erowid.org/experiences/exp.php?ID=34904 2008
3. https://www.erowid.org/experiences/exp.php?ID=63381
4. https://www.erowid.org/experiences/exp.php?ID=51301
5. https://www.erowid.org/experiences/exp.php?ID=37460 2004
6. https://www.erowid.org/experiences/exp.php?ID=20164 2004
7. https://www.erowid.org/experiences/exp.php?ID=16951 2004
8. https://drugs-forum.com/threads/how-to-smoke-fentanyl-patches-safely-non-gel-type.148708/
9. J Anal Toxicol. 2009 Oct;33(8):418-22. Potential biomarkers of smoked fentanyl utilizing pyrolysis gas chromatography-mass spectrometry. Nishikawa RK1, Bell SC, Kraner JC, Callery PS.
10. Chest. 2012 May;141(5):1321-1323. doi: 10.1378/chest.11-1462. Pulmonary alveolar proteinosis as a reaction to fentanyl patch smoke. Chapman E1, Leipsic J2, Satkunam N3, Churg A4.
11. Martin T, Woodall K, McLellan B. Fentanyl-related deaths in Ontario, Canada: Toxicological findings and circumstances of death in 112 cases (2002-2004). J Analyt Toxicol 2006; 30(8):603-610.
12. Marquardt K, Tharatt S. Inhalation abuse of fentanyl patch. Clin Toxicol 1994; 32(1): 75-78 - abstraact only
13. Schauer C, Shand J, Reynolds T. The fentanyl patch boil-up - a novel method of opioid abuse. Basic Clin Pharmacol Toxicol 2015; 117:358-359. http://onlinelibrary.wiley.com/doi/10.1111/bcpt.12412/pdf
*Pubmed "smoked/inhaled fentanyl

May. 15, 2017Is Concerta 72mg safe at 6 months pregnancy? details
 

Response: There is very little information regarding exposure of human pregnancies to methylphenidate.(1-4) Of the limited data available, there is no signal that methylphenidate, when taken at therapeutic doses, causes congenital malformations. The related drugs amphetamines, when taken at high doses (i.e. illegal, abusive use) may be associated with intrauterine growth restriction, miscarriage, high blood pressure, placental abruption, neonatal behavior, and central nervous system development disturbances.(3,5) There could also be a neonatal withdrawal syndrome.(5)
As such, pregnancy termination is not warranted based on methylphenidate exposure. The fetal growth should be monitored and after delivery, the infant should be observed for neonatal withdrawal syndrome (possibly presenting with trouble eating, sleeping too little or too much, having very floppy or tight muscles, and being very jittery[5]).
References: 1. Briggs
2. Drugs During Pregnancy and Lactation - Clinical Key
3. Micromedex - Reprotox
4. Micromedex - Teris
5. http://mothertobaby.org/fact-sheets/methamphetaminedextroamphetamine-pregnancy/
*Motherisk

May. 15, 2017One of our facilities accidentally purchased non-PVC IV bags that we use for amiodarone, nitroglycerin and chemo drugs. We have been asked if they can be used in place of PVC bags (i.e. to use them up) for all their other drugs? They order them from the cancer centre - Braun DEHP non-rubber, non-latex. details
 

Response: The Braun bags contain a copolymer of propylene and ethylene (formerly referred to as polyolefin).(2) Insulin, as an example, is a drug that has been found to adsorb to this material.(4) As such, compatability would need to be confirmed for each drug before using this IV bag. If the compatability has been examined, it will be in the Handbook of Injectable Drugs.(3)
References: 1. http://www.bbraunusa.com/8090.html
2. Phone communication with Sue, Braun customer service, 1-800-854-6851, May 15, 2017
3. Trissel's 2017 via SHIRP
4. Trissel L, Xu Q, Baker M. Drug compatibility with new polyolefin infusion solution containers. Am J Health-Syst Pharm. 2006; 63:2379-82

May. 15, 2017When using methotrexate ORALLY for medical termination of pregnancy, does the dose need to be adjusted for obesity? details
 

Response: Both the CPhA Methotrexate monograph(1) and the SOGC guidelines(2) consider the oral dose of MTX for medical abortion to be 50 mg. One study compared 25 mg to 50 mg; while both doses were considered effective, women in the 50 mg group passed the pregnancy more quickly.(3) Otherwise, studies have used either 50 mg(4) or 50 mg/m2 (5,6) without addressing weight.

The study that may be of most interest to you is from 1997 but is the only study I found that correlated weight with effectiveness.(7) It needs to be noted effectiveness as per weight was not a primary outcome but a multivariate analysis undertaken as a means to identify predictors of success. The researchers found an inverse linear relationship between body surface area (BSA) and success. This study used a dose of 50 mg. Completed abortion rates as per BSA quartiles were as follows:
BSA 1.38-1.62: 94.7%
1.63-1.74: 92.9%
1.75-1.82: 89.2%
1.83-2.36: 87.8%
As such, the authors suggest a higher dose or use of the IM route may be necessary for women with higher BSAs.
References: 1. RxTx [Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. CPS online: CPhA Methotrexate; [updated 01 Nov 2016; cited 16 May 2017]. Available from: https://www.e-therapeutics.ca/
2. Costescu D, Guilbert E, Bernardin J, et al; Society of Obstetricians and Gynecologists of Canada. Medical Abortion. J Obstet Gynaecol Can. 2016 Apr;38(4):366-89.10
3. Creinin MD. Oral methotrexate and vaginal misoprostol for early abortion. Contraception. 1996;54:321-327
4. Carbonell JL, Varela L, Velazxo A, et al. Oral methotrexate and vaginal misoprostol for early abortion. Contraception. 1998; 57: 83-88
5. Wiebe E, Dunn S, Guilbert E, Jacot F, et al. Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol. Obstet Gynecol 2002;99:813.
6. Wiebe ER. Oral methotrexate compared with injected methotrexate when used with misoprostol for abortion. Am J Obstet Gynecol 1999;181:149-152.
7. Creinin MD, Vittinghoff E, Schaff E, et al. Medical abortion with oral methotrexate and vaginal misoprostol. Obstet Gynecol. 1997; 90: 611-616

May. 16, 2017Can a patient receive the zoster vaccine while on two DMARDs? details
 

Patient Age: 77
Patient Sex: F
Medical Problems: RA
50 kg
Medication History: MTX 20 mg (0.4 mg/kg) once weekly
Hydroxycholoroquine
Response: Neither the American College of Rheumatology(1) nor the National Advisory Committee on Immunizations(2) consider Hydroxycholoroquine immunosuppressive. The ACR specifies patients taking combination DMARD therapy - which includes combinations of methotrexate, sulfasalazine, HCQ, or leflunomide - can have the zoster vaccine.(1)
References: 1.https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf
2.Jade/DrugFiles/Zoster vaccine/NACIHerpesZosterUpdate2013

May. 16, 2017Patient is on Estalis patch and it is shorted, as is the Climara Pro patch. What would be the next closest product? details
 

Response: No other combination patches are available.(1) The only other topical progesterone would be compounded progesterone cream; however, this does not provide endometrial protection.(1) As such, if she still needs progesterone (more than likely does), there do not appear to be any agents other than oral.(1)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Postmenopausal-RxandHerbal.pdf

May. 17, 2017Patient is having trouble with diarrhea (the worst it's ever been). MD has prescribed 1/2 packet cholestyramine BID at two biggest meals (noon and 1700h). How does it bind other drugs? We've tried to move some of her meds to breakfast but she takes Tylenol Arthritis, magnesium and tramadol at 1400h that can't really be changed. Will these be affected? details
 

Medical Problems: severe diarrhea
Medication History: tried loperamide
Tylenol, Mg, tramadol
Response: Cholestyramine has the potential to bind with many drugs and unless proven otherwise, should be assumed to bind a drug.(2) In general, other drugs should be taken one hour before or 4-6 hours after the cholestyramine.(2) There are limited data with acetaminophen showing minimal affect on absorption when cholestyramine is given one hour after acetaminophen.(1) It will not be possible to space the 1400 doses appropriately so patient's pain and magnesium levels will need to be monitored.
References: 1. Stockley's
2. CPhA Cholestyramine monograph

May. 17, 2017Patient has been on Xanax XR 1 mg daily as well as Prozac 40 mg daily since March. The psychiatrist here told him to reduce Prozac to 20 mg daily for 7 days, then stop. He has also started Pristiq 50 mg and is on quetiapine 25 mg for anxiety. The patient was told to only take the Xanax if absolutlely needed. He has 10 tablets left. I'm worried he may undergo some anxiety if the Xanax is stopped abruptly. Would this be the case? If so, how should it be tapered? details
 

Patient Age: 19
Patient Sex: M
Medical Problems: anxiety
Medication History: Prozac 40 mg -> 20 mg, Pristiq 50 mg. After 7 days stop Prozac
Xanax XR 1 mg
Response: Up to 30% of patients suggested to experience withdrawal after 8 weeks of benzodiazepine treatment.(3) This patient is on that cusp and there is a chance he won't experience withdrawal symptoms. It is feasible for him to abruptly discontinue the Xanax XR. He should report any intolerable withdrawal symptoms (insomnia anxiety, irritability, sweating, GI)(2), keeping in mind they should dissipate after a couple of days and fully resolve in a few weeks.(2)
References: 1. Micromedex
2. http://www.open-pharmacy-research.ca/wordpress/wp-content/uploads/benzodiazepine-deprescribing-information-pamphlet.pdf
3. Clinical Handbook of Psychotropic Drugs, 20th edition

May. 17, 2017Is Erivedge cytotoxic? Should our nurses be taking precautions with administration? Should our care aids be taking precautions considering they're exposed to the resident's fluids? details
 

Response: This drug is on the NIOSH list because of its teratogenic effects and classification as an antineoplastic agent.(2) The drug is a capsule(1) so caregivers administering the drug can wear gloves (single is fine) and, if there is a risk of splashing, eye and face protection.(2) Most of the drug is excreted in the feces unchanged; only 4% excreted renally.(1) As for those handling the patient's waste (particularly fecal), double chemotherapy gloves, protective gown, eye/face protection if liquid could splash are recommended.(2)
References: 1. RxTx - eCPS
2. https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf

May. 18, 2017Can hydromorphone 2mg/ml ampoules be pre-drawn into a syringe? details
 

Response: Depending on the syringe used, loss of hydromorphone concentration when stored >24 hours is possible. This has been reported when some drugs have been stored in BD syringes that used an alternate rubber stopper (to the original latex-free elastomer stopper).(1) BD told me, "As far as they know all of their syringes have the latex-free elastomer stoppers"(2), which doesn't instill a lot of confidence but even at that, if the syringes on hand were manufacturered a couple of years ago, they could have the alternate rubber stopper. How the stoppers of other manufacturers of syringes affects the concentrations is not known.(3) If BD syringes are used, it may be worthwhile contacting BD with the lot number to ascertain the composition of the stopper.
Otherwise, hydromorphone in concentrations of 1.5 mg/ml and 80 mg/ml have been found to be stable in 30 ml polypropylene syringes for up to 60 days when stored in the fridge and dark or at 23 deg C in fluorescent lighting.(1)
References: 1. Handbook of Injectable Drugs, 2017 via SHIRP
2. Phone communication with Christian, BD Customer Service, 1-866-979-9408 May 18, 2017
3. https://www.ismp-canada.org/download/presentations/LHSC2016-02_BDIssue.pdf
4. http://www1.bd.com/hypodermic/pdf/Sept_2016_Syringe_Notification.pdf

May. 18, 2017Patient is on Methotrexate 15 mg per week (takes on Wed). She has a knee replacement scheduled on June 5. Does she need to stop the methotrexate (because of immunosuppression)? details
 

Patient Sex: F
Medical Problems: RA
Medication History: Actemra (stopping for surgery)
MTX 15 mg once weekly
Response: Based on one randomized trial of patients on methotrexate for RA and undergoing elective orthopedic surgery, it is recommended to continue methotrexate.(2,3) In the study, the group in whom MTX was continued had better outcomes than those in whom it was discontinued 2 weeks prior as well as a control group of RA patients not taking MTX.(1)
References: 1. UTD - Perioperative medication management
2. Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis. 2001;60(3):214. PMID 11171680
3. Rheumatoid arthritis: Perioperative management of biologics and DMARDs. Goodman SM. Semin Arthritis Rheum. 2015 Jun;44(6):627-32. doi: 10.1016/j.semarthrit.2015.01.008. Epub 2015 Jan 30. Review. PMID: 25747348
*PL

May. 18, 2017I have an elderly patient who accidentally took 2x100 mg losartan (usually takes 100 mg). Do you have any information about harms? details
 

Response: ARBs seem to have a wide therapeutic window(1) such that she wouldn't be expected to experience any severe and likely not any mild effects. She'll just need to be careful when up and about and lie down more frequently today.
References: 1. Micromedex - Toxicology

May. 22, 2017I have a prescription from a dentist for my patient to take Valium 5mg X 5 tablets one hour prior to dental appointment. Is this something that is recommended? details
 

Patient Age: 19
Patient Sex: M
Response: Dosage recommendations are 5-10mg/dose given 1 hour prior to dental procedure. There appears to be some confusion in the prescribers order, and I would recommend the patient take the maximum recommended dose (10mg) one hour prior to the appointment, then clarify the dosing with the dentist when you arrive.
References: 1. Lexicomp
2. Micromedex

May. 23, 2017One of my elderly patients was interested in trying Chaga tea as he heard it was useful for diabetes management. I'm just looking for general information regarding this herbal product such as any evidence of benefit, side effects/risks, interactions with medications. details
 

Patient Age: 76
Patient Sex: M
Medication History: hydralazine, Adalat, terazosin, atenolol, rosuvastatin, ASA
Lantus, Novorapid,
allopurinol, nitro patches, Olmetec, Pantoloc,
Response: There has been no study of chaga in humans. From in vitro and in vivo animal studies, it appears it may have immunostimulant, antiplatelet, anti-inflammatory, and blood glucose lowering effects. (1,2) Sent link to (2) and Patient Handout from (1).
References: 1. Natural Medicines
2. https://www.mskcc.org/cancer-care/integrative-medicine/herbs/chaga-mushroom
*Lexicomp, Micromedex

May. 23, 2017A male patient from the Cancer Clinic said he is getting hot flashes and the oncologist prescribed venlafaxine. Is there any evidence of use for this in males? details
 

Response: There is evidence of use of venlafaxine 75 mg daily for treatment of androgen deprivation therapy-induced hot flashes in men with prostate cancer; while it was effective at reducing hot flash episodes, it was not as effective as medroxyprogesterone 20 mg daily or cyproterone 100 mg daily.(1)
References: 1. UTD - Side effects of androgen deprivation therapy

May. 23, 2017Can roflumilast be crushed and administered via an orogastric tube? details
 

Response: Similar to the caller, I found no specific information about crushing roflumilast.(*) However, as caller states, it is not a controlled release product. It is also neither on the do not crush list(1) nor the hazardous drug list(2) so if they are willing to risk a clogged tube, there appears to be no reason not to try.
References: 1. http://www.ismp.org/tools/donotcrush.pdf
2. https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf
*AHS Alt ROA, Handbook of Drug Administration via Enteral Feeding Tubes, PubMed

May. 23, 2017What is seradase? details
 

Response: Seradase is serrapeptase, promoted as an anti-inflammatory and mucolytic agent, but efficacy for either use has not been well established.(1) It has been well tolerated in short-term (1-2 weeks) clinical trials enrolling more than 1,400 patients, with an incidence of adverse effects similar to that with placebo. Hypersensitivity reactions and gastric pain have been reported.(1) It is not a prescription drug in Canada, but is a Natural Health Product for which several products have been licensed in Canada.(2)
References: 1. Lexicomp
2. LNHPD

May. 23, 2017Is there any data of rechallenging bisphosphonates in a patient who had osteonecrosis of the jaw that has healed? details
 

Response: There are no data so can only go by expert opinion from guidelines, which suggests to resume bisphosphonate therapy (for oncological indications) upon control of the osteonecrosis of the jaw (1-3). Some, in fact, only discontinue the bisphosphonate if the ONJ worsens with continued bisphosphonate therapy.(1)
References: 1. UTD - Medication-related osteonecrosis of the jaw in patients with cancer
2. Khan AA, Sándor GK, Dore E, et al; Canadian Association of Oral and Maxillofacial Surgeons. Canadian consensus practice guidelines for bisphosphonate associated osteonecrosis of the jaw. J Rheumatol. 2008 Jul;35(7):1391-7. Epub 2008 Jun 1. PMID 18528958
3. Khan AA, Morrison A, Hanley DA, et al; International Task Force on Osteonecrosis of the Jaw. Diagnosis and management of osteonecrosis of the jaw: a systematic review and international consensus. J Bone Miner Res. 2015 Jan;30(1):3-23. doi: 10.1002/jbmr.2405. PMID 25414052

May. 23, 2017Is pregabalin 75mg TID in an 11 year old for seizures appropriate? details
 

Medical Problems: probably seizures?
Medication History: VPA before this 750 mg per day
Response: There has been one phase I trial of pregabalin in children 1 month to 16 years old with refractory partial seizures. The children were given the drug for 7 days so long term safety is unknown. For a child of 11 years, the optimal dose (in terms of safety and tolerability) was 10 mg/kg/d.(3) Otherwise, the only other evidence is a case series of 19 children (4-15 years, mean 9.7) with partial seizure refractory to other anti-epileptics (mean failure of 5 drugs). The dose was 150-300 mg daily. It reduced the number of children with daily seizures from 74% to 37%; 26% withdrew due to ineffectiveness and it worsened myoclonic epilepsy in 11% (n=2).(4)
From the information provided by the caller, this child does not seem to be refractory at this point. The diagnosis of seizure is questionable and the caller needs to confirm the indication. That said, this dose has been used in children of this age.(3,4)
References: 1. Micromedex
2. Lexicomp
3. Mann D, Liu J, Chew ML, et al. Safety, tolerability, and pharmacokinetics of pregabalin in children with refractory partial seizures: a phase 1, randomized controlled study. Epilepsia. 2014 Dec;55(12):1934-43.
4. Pregabalin: preliminary experience in intractable childhood epilepsy. Jan MM, Zuberi SA, Alsaihati BA. Pediatr Neurol. 2009 May;40(5):347-50. doi: 0.1016/j.pediatrneurol.2008.12.016. PMID: 19380070
5. RxTx - CTC - Seizures and Epilepsy

May. 23, 2017Would a skin reaction to hydroxychloroquine cause cross-reactivity to chloroquine? details
 

Response: There is a report of 4 patients who experienced cutaneous reaction with HCQ and were subsequently treated with CQ. Three of the reactions were morbilliform eruptions that were often intensely pruritic. They all began within 3 weeks of initiation of therapy and resolved with discontinuation (and often prednisone). Two of these patients tolerated the CQ and one developed another morbilliform eruption. A fourth patient experienced erythoderma from HCQ and when rechallenged with CQ, developed truncal erythema and pruritus.(2)
References: 1. Lexicomp - QuiNIDine/QuiNINE Derivative Allergy (Drug Allergy and Idiosyncratic Reactions)
2. Pelle MT, Callen JP. Adverse cutaneous reactions to hydroxychloroquine are more common in patients with dermatomyositis than in patients with cutaneous lupus erythematosus. Arch Dermatol. 2002;138(9):1231-1233.[PubMed 12224986]

May. 24, 2017How does obesity affect the dosage requirements for these medications when given orally: 1) opioids 2) benzos 3) gabapentin details
 

Response: 1. General obesity dosing principles are as follows (1,2,3):
- Lipophilic drugs will have a higher volume of distribution (VD), and thus a longer half-life. This creates a longer time-to-steady-state, and also potential for drug accumulation for drugs with a long half-life (eg. Diazepam's half-life is greatly increased in obesity, possibly should use lower doses). For IV drugs that require loading doses, this means a higher loading dose would be required. This does not apply to all lipophilic drugs, however--highly variable.
- Hydrophilic drugs may have higher renal clearance in some obese individuals.
- Hepatic clearance may be increased in obese individuals, IF the person does not have fatty liver issues (which would decrease clearance). CYP2E1 and 3A4 activity is increased, as is glucuronidation. The magnitude of this is largely unstudied, and no clear dosing guidelines exist for drugs that may be affected by this.
- These principles tend to only be of clinical importance for low therapeutic index drugs, or certain IV drugs (anesthesia, IV emergency pain induction).

2. For opioid drug dosing:
- Almost all data available was for IV dosing in emergency situations, which suggest using Ideal Body Weight (which is unchanged in obese vs. non-obese) (4)
- Some studies show (5,6) opioid analgesia requirements post-OP were the same in obese vs non-obese individuals.
- No specific dosing guidelines of opioids in obesity available. Theoretically:
- Morphine is hydrophilic, so possible increased clearance, but this was highly variable and unpredictable. Not enough data to make recommendations (7)
- Hydromorphone is intermediate hydro/lipophilic. No data on pharmacokinetic changes in obesity.
- Fentanyl is lipophilic, leading to possible accumulation or prolonged effects, thus dosing based on IBW (vs. TBW) is safer (8).

3. For benzodiazepines:
- In general, most benzodiazepines are lipophilic, and thus concern with increased half-lives. This will mean steady-state will take longer to reach, and there is the potential for accumulation. (9)
- Some specifics (10):
- Alprazolam (lipophilic) had much longer half-life (11h to 22h) in obese vs. non-obese individuals. However, final AUC ended up being the same once steady-state reached. Metabolism and clearance unchanged.
- Triazolam's (more hydrophilic) half-life was slightly increased from 2.6 to 4.1h, and had a slightly greater AUC in obese individuals due to decreased clearance.
- Diazepam (11), at steady-state, achieves similar AUC in obese and non-obese patients, it just takes longer in obese patients.
- However, IV dosing is still based on IBW (4), so likely no need for alteration to oral dosing in obesity.

4. No specific data for gabapentin could be found. Gabapentin is hydrophobic, which may increase renal clearance and the need for higher maintenance doses; but there are no pharmacokinetic studies available to show this is true.
References: 1. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1374§ionid=74719619
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018176/
3. http://www.druginformation.co.nz/Bulletins/2008/012-Obesity.pdf
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018176/table/i1551-6776-15-2-94-t01/
5. http://www.smiss.org/abstract/opioid-requirements-obese-patients-following-minimally-invasive-transforaminal-lumbar
6. http://emj.bmj.com/content/31/2/139
7. https://www.ncbi.nlm.nih.gov/pubmed/19743886
8. https://www.ncbi.nlm.nih.gov/pubmed/16024584
9. Koda-Kimble Pharmacology book: https://books.google.ca/books?id=qcVpuHngXK0C&pg=PA1880&lpg=PA1880&dq=obesity+benzodiazepine&source=bl&ots=E1CK2_qawb&sig=YC4Ox_l_wQiiLnSK7xmuZ1Mgn6M&hl=en&sa=X&ved=0ahUKEwjoxezBvonUAhXD6oMKHZ2gBuQQ6AEIQDAF#v=onepage&q=obesity%20benzodiazepine&f=false
10. https://www.ncbi.nlm.nih.gov/pubmed/6143633
11. http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1983.tb02750.x/abstract

May. 26, 2017I need to know the specific areas of the gut where Isoniazid and rifampin are absorbed, and if tube placement and direct drug delivery to this area will increase absorption. details
 

Patient Age: 32
Patient Sex: M
Medical Problems: tuberculosis
Medication History: oral isoniazid,rifampin,levofloxacin,ethambutol,pyrazinamide, pyridoxine
Response: The absorption sites of isoniazid and rifampin are unknown and I found no information regarding use of tubes for targeted administration. (1,*)

I did find information about malabsorption of TB drugs in TB patients (compared to healthy volunteers).(7) There has been suggestion to obtain two serum levels – one at 2 h and the other at 6 h.(9) The reason for this is that a low 2 h level may simply indicate delayed absorption, not malabsorption. If the 6 h level is higher than that of the 2 h, the peak concentration likely occurred between the two sample times and the patient can be counselled to take the drugs on an empty stomach. Should the 6 h levels also be subtherapeutic, a dose increase is warranted; however, the authors simply recommend increasing the doses to achieve target concentrations (9). Certainly, one would not expect toxicity with higher doses if malabsorption is indeed the cause of the low levels.
I looked quickly (not enough time for a complete search) of reports of increasing TB drug doses in response to low concentrations. I only found one study, which was conducted in a specific population of TB patients with diabetes.(10) Patients whose 2 h concentrations for isoniazid and/or rifampin were below the defined therapeutic range were given a higher dose: from 600 mg to 900 mg daily for rifampin and from 300 mg to 450 mg daily for isoniazid. Therapeutic concentrations were achieved in 12 of 15 patients whose doses were increased due to subtherapeutic 2 h values. Unfortunately, only the mean concentration is reported for the patients with and without diabetes, not patient-specific data. Therefore, it is quite possible those who did not achieve therapeutic concentrations may have had exceptionally low initial values, such as your patient. The authors acknowledge by using a lone 2 h level some patients with delayed absorption may have been erroneously categorized as malabsorptive, though they contend if this were the case adverse effects/toxicity would be expected.
Given the limitations you state for IV therapy, the team may want to consider increasing the doses above the usual maximum recommended daily doses and re-evaluating the concentrations and adverse effects. Certainly this may have already been tried and, if not, I understand this strategy is met with cost implications, though I suspect the cost would be lower than IV administered drugs. My understanding is these drug levels are not readily available in Canada; this and the lack of evidence to support this strategy are further significant limitations.
References: 1. Handbook of Drug Administration via Enteral Feeding tubes (online thru library) 2011
2. Bioequivalence trials of rifampicin containing formulations: extrinsic and intrinsic factors in the absorption of rifampicin. Agrawal S, Singh I, Kaur KJ, Bhade S, Kaul CL, Panchagnula .
Pharmacol Res. 2004 Sep;50(3):317-27. PMID: 15225676
3. AHS Compounding Manual
4. AHS Alt Route Admin
5. UTD - Antituberculous drugs: An overview
6. UTD - Treatment of drug-susceptible pulmonary tuberculosis in HIV-uninfected adults
7. Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis. Pinheiro VG, Ramos LM, Monteiro HS, Barroso EC, Bushen OY, Façanha MC, Peloquin CA, Guerrant RL, Lima AA. Braz J Infect Dis. 2006 Dec;10(6):374-9. PMID: 17420908
8. Therapeutic drug monitoring in the treatment of tuberculosis. Peloquin CA. Drugs. 2002;62(15):2169-83. Review. PMID: 12381217
9. Drugs. 2014 Jun;74(8):839-54. doi: 10.1007/s40265-014-0222-8. Therapeutic drug monitoring in the treatment of tuberculosis: an update. Alsultan A1, Peloquin CA. PMID 24846578
10. Tuberc Res Treat. 2013;2013:129723. doi: 10.1155/2013/129723. Epub 2013 Nov 17. Early Therapeutic Drug Monitoring for Isoniazid and Rifampin among Diabetics with Newly Diagnosed Tuberculosis in Virginia, USA. Heysell SK1, Moore JL2, Staley D2
11. A dose-ranging trial to optimize the dose of rifampin in the treatment of tuberculosis. Boeree MJ, Diacon AH, Dawson R,; PanACEA Consortium.. Am J Respir Crit Care Med. 2015 May 1;191(9):1058-65. doi: 10.1164/rccm.201407-1264OC. PMID: 25654354
*PubMed

May. 28, 2017A patient accidentally took 2 doses of alendronate 70 mg last Sunday. Anything we need to worry about? details
 

Medical Problems: -patient otherwise well
Response: No overdosage information available. Given other medications in the class can be taken in higher doses less frequently (eg, risedronate), unlikely to be of concern. With both etidronate and pamidronate, extreme doses of 10-fold resulted in hypocalcemia.
References: <1> Lexi-Drugs

May. 29, 2017What is the stability of Depo-Medrol multidose after it's been punctured? details
 

Response: According to USP guidelines, multidose vials are stable for 28 days following puncture unless otherwise specified by the manufacturer.(1) Considering there is nothing mentioned in the monograph of Depo-Medrol regarding stability after puncture (2), default to 28 days.
References: 1. https://www.cdc.gov/injectionsafety/providers/provider_faqs_multivials.html

May. 30, 2017Can you look for evidence of increasing rifampin and isoniazid dosing based on plasma levels? details
 

Response: Below is the data I have found re: use of therapeutic drug monitoring (TDM) for TB drugs. It seems there may be more success with using TDM for rifampin (RIF) than isoniazid (INH).

Mehta, 2001(2)
- Of 124 patients, 6 were slow responders (3 months) so RIF levels taken 1.5-2.5 h post-dose.
- All were subtherapeutic (therapeutic range defined as 8-24 mcg/mL) -> RIF increased from 600 mg daily to 900 mg daily
- All achieved therapeutic levels at 900 mg except 1 patient required dose of 1500 mg daily for therapeutic levels
- All responded clinically once in therapeutic range
- No adverse effects reported

Ray, 2003(3)
- A qualitative study of usefulness of a TDM clinic
- 90 levels measured for various reasons: routine (62); toxicity (3); failure (10); malabsorption (2); interaction (1); compliance (2)
- RIF levels taken 1-3 h post-dose; doses varied from 150 mg to 750 mg
- INH levels taken 1-3 h post-dose; doses varied from 150 mg to 750 mg
- 46% RIF subtherapeutic (therapeutic range defined as 10-29 mcg/mL)
- 48% INH subtherapeutic; 29% supratherapeutic (therapeutic range defined as 22-37 mcg/mL)
- Includes a case example of patient with slow response whose RIF and INH were subtherapeutic; doses increased, therapeutic levels achieved as well as clinical response

Heysell, 2010(4)
- Retrospective cohort study to determine prevalence of subtherapeutic levels
- 42 patients, slow to respond
- RIF and INH levels drawn 2 h post-dose; therapeutic defined as 8-24 mcg/mL and 3-6 mcg/mL, respectively
- 52% subtherapeutic RIF levels; 59% subtherapeutic INH levels
- Median RIF dose increased from 600 mg to 900 mg daily and for INH from 300 mg to 450 mg daily
- 18 RIF levels rechecked: 89% therapeutic after first dose increase
o 14 finished, all with clinical success
- 14 INH levels rechecked: 29% therapeutic after first dose increase
- No reported adverse events

Babalik, 2011 (5)
- Retrospective case control study (patients with TB undergoing TDM matched to those with TB and no TDM)
- 20 had TDM due to slow clinical response, undergoing concomitant treatment or had comorbid illnesses that led to uncertainty of correct dosing.
- RIF and INH levels drawn 2h post-dose; therapeutic ranges stated as “published reference ranges from studies in human volunteers”.
- RIF dose 10 mg/kg up to 600 mg daily; INH 5 mg/kg up to 300 mg daily; dose increases at discretion of physician
- 17 patients had at least one low level of RIF, INH, rifabutin and/or pyrazinamide
o 67% of RIF levels measured were subtherapeutic; mean dose increased 50%
o 87% of INH levels measured were subtherapeutic; mean doses increased 60%
- Mean time to culture conversion 7.8 weeks in those with low levels compared to 3.3 weeks in those with adequate levels (nonsignificant)

Magis-Escurra, 2012 (6)
- Case series of patients undergoing TDM (slow response, relapse, abnormal concentrations suspected for other reasons)
- Therapeutic ranges RIF: 8-24 mg/L; INH: 3-5 mg/L; levels drawn at 2 h post-dose
- n=4
- Case 1
o RIF: 5.6 mg/L -> 15.2 mg/L after increase dose from 600 mg to 1200 mg.
o INH: undetectable -> 0.04 mg/L (dose increase not stated)
o Clinical improvement 2 weeks after dose increase; sputum culture conversion 6 weeks after
o No adverse effects
- Case 2
o Had to stop pyrazinamide due to GI intolerance; positive sputum at 4 months
o RIF 4.1 mg/L -> 22.4 mg/L after increase dose from 600 mg to 1200 mg
o Sputum culture conversion 1 month after dose increase
- Case 3
o Gastric surgery concern of absorption
o RIF 4 mg/L at 4h (deemed peak; it is unclear how many levels were drawn) -> 8.5 mg/L after 2 dose increases from 450 mg to 900 mg
o Sputum culture conversion 8 weeks after 2nd RIF dose increase
o No adverse effects
- Case 4
o Sputum conversion at 6 weeks but slow to respond clinically and radiologically
o At 12 weeks, RIF 2.3 mg/L -> 8.2 mg/L after increase dose from 600 to 900 mg; Levels at 4 h and 6 h were 3.6 and 1.6 mg/L, respectively; increased dose to 1200 mg
o Improved clinically after 2nd dose adjustment

Van Tongeren, 2013 (7)
- Case series of TDM results from 52 inpatients (76 episodes)
- Levels drawn 2h post-dose; “normal drug levels were as defined by the reference laboratory site criteria”
- 68.4% RIF levels subtherapeutic, median 3.81 mcg/mL -> median dose increase 300 mg -> median 7.1 mcg/mL (9 patients had been remeasured; levels decreased in 2 patients despite increased dose)
- 76.6% INH levels subtherapeutic, median 0.97 mcg/mL -> median dose increased 150 mg -> median 3.11 mcg/mL (levels remeasured in 17 patients)
- No info re: clinical improvement
References: 1. Verbeeck RK, Günther G, Kibuule D, et al. Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring. Eur J Clin Pharmacol. 2016 Aug;72(8):905-16. doi: 10.1007/s00228-016-2083-4. Epub 2016 Jun 15. Review.PMID: 27305904
2. Mehta JB, Shantaveerapa H, Byrd RP Jr, Morton SE, Fountain F, Roy TM (2001) Utility of rifampin blood levels in the treatment and follow-up of active pulmonary tuberculosis in patients who were slow to respond to routine directly observed therapy. Chest 120:1520–1524
3. Ray J, Gardiner I, Marriott D (2003) Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid. Intern Med J 33:229–234
4. Heysell SK, Moore JL, Keller SJ, Houpt ER (2010) Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, USA. Emerg Infect Dis 16:1546–1553
5. Babalik A, Mannix S, Francis D, Menzies D (2011) Therapeutic drug monitoring in the treatment of active tuberculosis. Can Respir J 18:225–229
6. Magis-Escurra C, van den Boogaard J, Ijdema D, Boeree M, Aarnoutse R (2012) Therapeutic drug monitoring in the treatment of tuberculosis patients. Pulm Pharmacol Ther 25:83–86
7. Van Tongeren L, Nolan S, Cook VJ, FitzGerald JM, Johnston JC (2013) Therapeutic drug monitoring in the treatment of tuberculosis: a retrospective analysis. Int J Tuberc Lung Dis 17:221–224

May. 30, 2017In the Canadian Tuberculosis guidelines, they state that high doses of pyridoxine can interfere with isoniazid activity. What is the mechanism of this inhibition and at what doses of pyridoxine are they referring too? Also does pyridoxine inhibit the GI absorption of Isoniazid? details
 

Response: I have been unable to find any evidence that pyridoxine interferes with INH activity. As you know, the purported mechanism of pyridoxine deficiency is competitive inhibition of the enzyme pyridoxal phosphokinase as well as increased urinary excretion of pyridoxine.(1) INH is a prodrug that is activated by a catalase peroxidase (KatG) endogenous to M tuberculosis,(2) and pyridoxal phosphokinase is not involved in any part of the metabolic pathway of INH.(1)

As you suggest, the next possibility is reduced absorption of INH with concomitant use of pyridoxine. The only information I found addressing this possibility is a rat study.(3) The authors of this study found that pyridoxine does reduce intestinal absorption of INH in a concentration-dependent manner. One of the suspected mechanisms is use of the same transporter. I interpret from this data that separating the administration of the two would circumvent the interaction.

The pyridoxine dose threshold suggested by the Standards and the CPhA monograph of INH(4) is 25 mg daily. Do you have a patient who requires a dose of pyridoxine >25 mg daily? If so, I could dig further by contacting the editor of the Standards for the reference used to support the statement; however, I suspect it will be a process to identify who wrote the section and to obtain the reference(s). If this is a theoretical question, I will leave it at this.
References: 1. Hernon C. Antituberculous Medications. In: Hoffman RS, Howland M, Lewin NA, Nelson LS, Goldfrank LR. eds. Goldfrank's Toxicologic Emergencies, 10e New York, NY: McGraw-Hill; 2015. http://accessemergencymedicine.mhmedical.com/Content.aspx?bookid=1163§ionid=65095861. Accessed May 31, 2017.
2. Metcalfe C, Macdonald IK, Murphy EJ, et al. The tuberculosis prodrug isoniazid bound to activating peroxidases. J Biol Chem. 2008 Mar 7;283(10):6193-200.
3. Zhou Y, Jiao Y, Wei YH, et al. Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats. Eur J Drug Metab Pharmacokinet. 2013 Mar;38(1):5-13.
4. RxTx [Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. CPS online: Isoniazid; [updated 01 Oct 2013; cited 31 May 2017]. Available from: https://www.e-therapeutics.ca/

May. 30, 2017Are any of these meds associated with drug-induced lupus? None of them correlate temporally with onset of lupus-type symptoms. details
 

Medication History: Humira (adalimumab)
Sublinox (zolpidem)
Estrogen
Progesterone
Dessicated thyroid
MTX
Prednisone
Hydroxychloroquine
Omeprazole
Response: 1. Of the drugs your patient is on, I could only find a possible link for Adalimumab, Estrogen/progesterone, and omeprazole (1,2,3)

2. Adalimumab and its link to SLE is thoroughly reviewed here (4):

- “Post marketing studies on the three licensed anti-TNF-α agents have suggested that the estimated incidence of ATIL is 0.19%–0.22% for infliximab, 0.18% for etanercept, and 0.10% for adalimumab. The onset of symptoms ranges from less than one month to more than 4 years.
- Can cause cutaneous or systemic manifestations, but most commonly cutaneous. "The cutaneous features of ATIL are most commonly malar rash, pruritic rash, photosensitive rash, or purpura."
- “However, in most reported cases, the diagnosis was made based on the development of one or more symptoms consistent with SLE, ongoing exposure to an anti-TNF-α agent, no prior history of SLE, and resolution of symptoms when the offending drug was discontinued. “
- Symptoms resolve within three weeks to six months after withdrawal of the implicated drug .

3. A recent systemic review / meta-analysis was done about OC use or HRT and its link to SLE (5). Their conclusion:

- “In the studies included in the present meta-analysis, OC and HRT generally did not affect the course of lupus activity at a clinically significant level. Two randomized clinical trials of HRT vs. placebo failed to find differences in disease activity or the incidence of severe flares in the two groups; however, one found the incidence of mild to moderate disease and the probability of suffering flares of any type were higher in the group that received HRT. The results of this clinical trial are in contrast with other cohort and case control studies in which there were no differences in the rate of flares nor in the disease activity scores in postmenopausal women with SLE treated with HRT compared with postmenopausal SLE women not treated with HRT. Interestingly, Kreidstein found that although there was not a difference in the incidence of total flares, pure serological flares were more common in HRT users and clinical flares more common in non-users.”

4. Omeprazole has some link as well, though weaker than adalimumab.
- A case-series (6) reports on 21 patient cases of SLE caused by PPIs. On average, it took 8 months (but up to 3.5 years) to develop SLE, and ~3 months to resolve once the PPI was discontinued.
- A systematic review (7) concluded that the evidence is limited to case reports, such as in (6), but PPIs should be considered a possible culprit for SLE development if there is no other suspected cause.
References: 1. Micromedex
2. SIDER database
3. Medeffects Canada, post-marketing report database
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504723/
5. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104303
6. http://onlinelibrary.wiley.com/doi/10.1111/bjd.12699/full
7. http://onlinelibrary.wiley.com/doi/10.1111/bjd.12832/full

May. 30, 2017Any issue giving prevnar-13 and zostavax simultaneously, or how long must they be separated? (eg. Pneumovax-23 and zostavax has rules around this) details
 

Response: 1. They can be given simultaneously; additional, the warning about pneumo-23 and HZ simultaneously has been removed, as it has not resulted in decreased efficacy with newer studies (the warning was just based on a theoretical concern by the FDA) (1,2). Even if they are not administered simultaneously, they can be administered any time before or after each other. (3)
References: 1. Health Can Imm Guide part 4 for pneumococcal vaccines
2. ", for shingles
3. ", part 1, timing of immunizations
4. http://www.immunize.org/askexperts/experts_pneumococcal_vaccines.asp

May. 31, 2017Is Myobloc available in Canada? details
 

Medical Problems: Cervical dystonia - seems to be getting antibodies to botulinum A
Response: While the drug has been approved in Canada(1) it is not necessarily marketed - considering the manufacturer suggested it is not available and SAP does not have it, there is no way to get it.
References: 1. DPD

May. 31, 2017A patient is agitated and MD (psychiatrist) wants to switch from 2 mg BID risperidone to loxapine. What is the best way to switch? details
 

Response: While there is no established or best strategy for switching, a cross taper where the risperidone is slowly tapered (e.g. 25% per week or every 2-4 weeks) while the loxapine is titrated (start at 25% of target dose and increase at same rate as risperidone reduction) would be an appropriate option. (2,4) Confirmed the prescribed is a psychiatrist considering switching from a 2nd generation to first generation antipsychotic is not typical.(1)
References: 1. http://switchrx.ca/antipsychotics.php/switch/risperidone-oral-to-loxapine-oral-
2. http://wiki.psychiatrienet.nl/index.php/Risperidone-Rest_AP
3. CPhA Loxapine monograph
4. Clinical Handbook of Psychotropic Drugs, 20th Ed., pg 175

Jun. 1, 2017How would a patient on a 87mcg fentanyl patch and on tramadol 350mg/d convert to hydromorphone contin / IR? details
 

Response: 1) Converting from fentanyl to another oral opioid, especially when tramadol is involved, will be inexact. For simplicity, I suggest ignoring the tramadol component and basing their starting dose of hydromorphone just based on the fentanyl component, and then titrating up from there. Additionally, for the first few days, the patient should just be given hydromorphone IR to allow for finding the new effective dose more easily. Once that is found, then converting to hydromorphone contin plus the IR for breakthrough pain can be done.

2) Most calculators and guidelines (1-3) suggest the 87.5mcg/hr of fentanyl is roughly equivalent to 30-45mg of hydromorphone.

3) The following is a suggested method to convert safely from Fentanyl to an oral opioid (3):

• Remove the fentanyl patch.
• For the first 12 hours after patch removal, use only the previously prescribed rescue opioid only for pain that occurs.
• Twelve hours after patch removal, begin with 50% of the calculated scheduled opioid regimen, and continue to offer the rescue opioid as needed.
• Twenty-four hours after patch removal, increase to 100% of the calculated scheduled opioid regimen, and continue to offer the rescue opioid as needed.
Here is a worked example, using morphine, from the resource above:
“BL is a 52 year old man admitted to your hospice program with a diagnosis of lung cancer;
he is receiving 50 mcg/h fentanyl with MSIR 15 mg po q2h prn breakthrough pain…
BL is agreeable to switching to sustained release morphine tablets. You use the 2 mg oral morphine:1 mcg fentanyl rule, and calculate an approximate total daily dose of oral morphine of 100 mg. But how do we make this switch—how do we time taking off the patch, and beginning
the morphine therapy?

In the case of BL, even though we have a good idea that fentanyl 50 mcg/mL is equivalent to
100 mg/day of oral morphine, you decide to move first to using the oral morphine he has in the home on an around the clock basis before ultimately switching him to oral sustained-release morphine tablets. So, let’s take a look at how we do this. After removing the patch, you instruct the patient to wait 12 hours before taking scheduled doses of oral morphine, however he is welcome to use the morphine 15 mg every 2 hours as needed for breakthrough pain. Based on our rule of thumb of fentanyl 50 mcg/ hour is equivalent to 100 mg oral morphine per day, we determine the 4-hourly dose of oral morphine to be 15 mg. Twelve hours after the patch is removed we instruct BL to take 50% of the calculated dose of morphine, which would be MSIR 7.5 mg po q4h (with rescue opioid still available). After 24 hours BL is instructed to increase to MSIR 15 mg po q4h around the clock. After two days of this regimen, he is switched to sustained-release oral morphine 45 mg po q12h, keeping the MSIR 15 mg po q2h prn breakthrough pain.”

Adapting that example to your patient would look like this (4):
• Fentanyl 87.5mcg/hr is roughly equivalent to 175mg morphine, or ~40mg hydromorphone
• The patient can use their tramadol IR* as the rescue medication, for now.
• Remove the fentanyl patch and allow the patient to take tramadol IR q4h as needed during this time.
• 12 hours after the patch is removed, the patient should start taking 50% of the calculated hydromorphone dose (20mg) as hydromorphone 4mg IR scheduled every 4 hours (max 5 per day), with the rescue dose option of tramadol still available.
• 24 hours after patch removal, the patient can start taking the full calculated hydromorphone dose as hydromorphone IR 8mg scheduled every 4 hours (max 5 per day), with the rescue option still available.
• Once this is done for a few days, can then convert to hydromorphone contin (either 18mg BID or 24mg BID), while also providing 2mg IR tablets for breakthrough pain.

*If patient does not have enough tramadol for this, they could be given hydromorphone 2mg IR as the breakthrough pain option instead.
References: 1. http://www.globalrph.com/opioidconverter2.cgi
2. https://opioidcalculator.practicalpainmanagement.com/conversion_results
3. https://www.ashp.org/-/media/store-files/p1985-sample-chapter-5.ashx
4. http://scp.in1touch.org/uploaded/web/refmanual/REF_Opioids_Switching_Tables_Current.pdf

Jun. 1, 2017Can sublingual suboxone tablets be split? details
 

Response: 1. Generally, sublingual tablets should not be split, as they crumble easily, it may not be accurate, and the remaining half may start degrading. The half being taken may also release slightly faster. (1)

2. However, there are plenty of online addictions forums with anecdotal reports of people splitting them to help with tapering (5), and I did find one Ontario addictions center guidelines for suboxone, which does suggest splitting the tablets to speed dissolution for witness doses (but not to administer the other half later) (2). A Veterans Affair insurance company also suggests the SL tablets can be split for easier dose adjustment (3). Officially, the monograph strongly suggests against splitting (4).

3. Based on this, the first dose of 1.5 8mg SL tablets would likely be close to 12mg, but the second one may be slightly less due to unknown stability. Other options would include giving a mix of dosage forms (2 and 8mg SL tablets), or if his stable dose has been found, alternate day dosing is possible--eg if 8mg per day is his stable dose, then he can take 16mg one day, 0 the next, 16mg the next, etc. (4)

4. I could not find any information about alternating different strengths each day to achieve an "average" daily dose, unfortunately. However, based on the alternate day regimen suggested in the monograph, and the pharmacokinetics of buprenorphine, it does theoretically make sense (eg. 8mg day 1, 16mg day 2, 8mg day 3, 16mg day 4 = average of 12mg per day, which is similar to the monographs alternate day regimen.)
References: 1. http://www.medscape.com/viewarticle/807030_4
2. http://www.ocpinfo.com/library/practice-related/download/Buprenorphine%20for%20the%20Treatment%20of%20Opioid%20Dependence.pdf
3. https://www.pbm.va.gov/clinicalguidance/abbreviatedreviews/BuprenorphineSLFilmSuboxoneAbbreviatedReview.doc
4. Suboxone monograph
5. Google search

Jun. 2, 2017Any interactions between azithromycin, acetaminophen, naproxen and morphine? details
 

Response: There are no interactions of note.(1,2) A vague possible interaction is that azithromycin may increase morphine levels due to PGP inhibition(1); however, this is not documented with these two drugs and morphine would be titrated to effect.
References: 1. Lexicomp
2. Stockley's

Jun. 12, 2017Any new evidence for direct anticoagulants for medical management of stroke prevention in aortic disease? details
 

Patient Age: 87
Patient Sex: F
Medical Problems: 60.7kg
End-stage CHF
Patent Foramen Ovale with left to right shunt
Severe Aortic calcification
Mild left ventricular hypertrophy
CHADS2-VASC = 5-6
Medication History: CITALOPRAM HYDROBROMIDE 10 mg TABLET
0.5 Tablet(s), QAM
LAX-A-DAY 17 GRAM/DOSE POWDER (17G/DOSE)
17 g, QD PRN
RAMIPRIL 2.5 mg CAPSULE
1 Capsule(s), QD
RANITIDINE HCL 150 mg TABLET
1 Tablet(s), BID
SPIRONOLACTONE 25 mg TABLET
0.5 Tablet(s), QAM
TYLENOL ARTHRITIS ER 650 MG TB
1 Tablet(s), BID
WARFARIN SODIUM 1 mg TABLET
1.5 mg, QD
E# FUROSEMIDE 20MG TABLET
3 Tablet(s), QAM
E# MIRTAZAPINE 15 mg TABLET
0.5 Tablet(s), QHS, 1 Week(s)
then 1 Tablet(s), QHS, 3 Week(s)
E# POTASSIUM CHLORIDE 8 mEq (600 mg) TABLET, EXTENDED RELEASE
1 Tablet(s), QD
Response: 1. There is currently insufficent data to answer the exact benefit DOACs may have in HF / CAD patients in sinus rhythm (1-7). There is only one on-going trial (COMMANDER-HF) at the moment (2) which is investigating if DOACs will be safe or effective in this population.
2. Some groups (3) consider using DOACs in this setting to be an inappropriate alternative to warfarin, due to lack of evidence.
3. The only data for DOACs use in CHF come from the original trials of these agents, which were all Afib patients (4). It was found that the efficacy of the DOACs were the same regardless of if the patient had heart failure or not. However, this cannot be extrapolated to patients without Afib.
4. Other organizations recomment anticoagulation in heart failure in the following scenarios (5):
ESC: HF with Afib or HF with previous thrombo-embolism or intracardiac thrombus
AHA: HF with Afib, or previous thrombo-embolism, mobile LV thrombus
HFSA: HF with Afib, or previous thrombo-embolism, LV thrombus, recent anterior MI with low EF
5. For your patient, if it was felt that they benefit from anticoagulation with warfarin (have they had a previous MI, stroke or TIA?), then a DOAC is a reasonable alternative, but there is no direct evidence to support going this route.
References: 1. http://www.heartfailure.onlinejacc.org/content/2/1/1
2. https://www.clinicaltrials.gov/ct2/show/NCT01877915?term=NCT01877915%26rank=1
3. UpToDate, Antithrombotic therapy in patients with heart failure
4. http://www.rimed.org/rimedicaljournal/2017/05/2017-05-18-thromboembolic-riley.pdf - 2017 lit review
5. http://www.imetha.gr/pdf/presentations/alpic2016/saturday/100-filippatos%20DOACs%20in%20HF%20ALPIC%202016%20finale.pdf
6. https://www.wjgnet.com/1949-8462/full/v9/i5/422.htm
7. https://link.springer.com/chapter/10.1007/164_2016_126
8. Medline Literature search: (DOAC or NOAC) AND (heart failure – all types) OR CAD

Jun. 12, 2017What is the proper dose of Epipen (adrenaline / epinephrine) in a 9 month old weighing 7kg? details
 

Response: The current recommendations are that patients weighing 10 kg to 25 kg should be prescribed EpiPen Jr, while those weighing more than 25 kg should be prescribed EpiPen. For patients weighing less than 10 kg, physicians and families will need to weigh the benefits and risks of administering epinephrine via syringes after being drawn up by a family member from small ampules. This method has been shown to be both error and delay prone, and family members must be fully competent before choosing this method of administration.(2) One allergist (as opinion) points out there is no research to support that 0.01 mg/kg is the 'correct dose'. (3) The adverse effects of too much epinephrine include elevations in the mean systolic pressure, pallor, tremor, anxiety, and palpitations, though they appear to be transient and unlikely to be serious in a young child without known cardiovascular disease.(3)
References: 1.UTD - Prescribing epinephrine for anaphylaxis self-treatment
2. POSITION STATEMENT Canadian Pediatric Society - Emergency treatment of anaphylaxis in infants and children. Posted: Jan 1 2011 Reaffirmed: Feb 1 2016 - http://www.cps.ca/documents/position/emergency-treatment-anaphylaxis
3. https://www.aaaai.org/ask-the-expert/dose-epinephrine-infant

Jun. 16, 2017In the monograph it states not to initiate a SGLT-2 inhibitor if eGFR is under 60, due to the lack of effect the medication would have. How true is this? details
 

Response: Regarding canagliflozin, data exists for A1c lowering in patients with stage 2 and stage 3 chronic kidney disease (CKD) (1-3), including patients with eGFR as low as 30 ml/min (3). Two of the papers are post-hoc analyses of pooled data (2,3) and only one was designed to assess the CKD population (1). I can understand not approving use in those with eGFR between 30 and 45 ml/min based on post-hoc analysis but there has been no indication of harm in this population. While the American and Canadian dosing are the same for canagliflozin, the thresholds for contraindications are different and I’m not sure on what the Canadian threshold would be based.

A study has been conducted of dapagliflozin in patients with eGFR 30-60 ml/min (4). The patients in this study did not achieve greater improvement in HbA1c; however, there was no more harm, and in fact they had improved weight loss and blood pressure reductions compared to the placebo group. Therefore, I cannot understand the contraindication in Canada – sure it doesn’t work so keep the label that it should be discontinued if <60 ml/min but a contraindication does not seem justified.

Direct evidence is available to suggest empagliflozin reduces A1c in patients with eGFR as low as 30 ml/min, but that it is ineffective in those with eGFR < 30 ml/min (5). The average eGFR in the patients in this study with Stage 3 CKD was 45 ml/min, which I suspect is the reason the FDA chose that threshold for discontinuation. This study also included patients with Stage 4 CKD (eGFR 15-30 ml/min) and while empagliflozin did not cause more adverse events than placebo in patients with CKD Stages 2 or 3, there were more adverse events reported in those with Stage 4 (though most were mild or moderate). Perhaps this explains the FDA’s threshold of 30 ml/min as a contraindication.

While I can justify the FDA dosing for these drugs, I am not sure on what reasons the doses of Health Canada are based.
References: 1. Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes mellitus and chronic kidney disease. Diabetes Obes Metab. 2014;16(10):1016–27.
2. Roussel R, de Zeeuw D, Law G, et al. Efficacy and safety of canagliflozin (CANA) in patients with type 2 diabetes mellitus (T2DM) who progressed to stage 3A chronic kidney disease during treatment (abstract). Diabetologia. 2014;57(Suppl 1):S322–3 (abstract 799).
3. Yamout H, Perkovic V, Davies M, et al. Efficacy and safety of canagliflozin in patients with type 2 diabetes and stage 3 nephropathy. Am J Nephrol. 2014;40(1):64–74.
4. Kohan DE, Fioretto P, Tang W, et al. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int. 2014;85(4):962–71.
5. Barnett AH, Mithal A, Manassie J, et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369–84.

Jun. 16, 2017Regarding your phosphate shortage document, am I to believe I can use the ratio of 16.1 mmol P per 500 mg from the tablets to the liquid? details
 

Response: Yes, this is correct. 500 mg phosphorus is obtained in 3.86 ml solution that contains 2.4 g monobasic sodium phosphate and 0.9 g dibasic sodium phosphate.(1)
References: 1. http://medsask.usask.ca/documents/drug-shortages/Sodium%20Phosphate.pdf

Jun. 16, 2017Is paresthesia caused by amiodarone a potentially serious reaction? details
 

Patient Sex: M
Medical Problems: arrhythmia
Medication History: propafenone - not effective
amiodarone - is effective and is willing to put up with the side effect 400 mg PO BID x 2 weeks followed by 200 mg PO BID
Response: While there is not much information about paresthesia specifically (1), peripheral neuropathy including muscle weakness, loss of sensations, and absence of tendon reflexes (1) but also with paresthesia (2) has been reported commonly with amiodarone treatment. It is thought to be dose-dependent (1,2) and much less common in daily doses of 400 mg or less. These effects have been reported to be irreversible in some patients though other patients have recovered partially or completely with dose reduction or discontinuation (1). As this patient is currently receiving a loading dose, it is quite possible symptoms will abate with the dose reduction.
References: 1. DrugDex
2. UTD - Type and incidence of major side effects associated with amiodarone therapy

Jun. 20, 2017Patient has been on Seasonique; MD has prescribed Activelle (estradiol 1 mg) and said there is less estrogen with the Activelle. Is this true? details
 

Response: Seasonique contains 30 mcg ethinyl estradiol (1) and Activelle contains 1 mg estradiol hemihydrate.(2) Ethinyl estradiol 5 mcg = estradiol hemihydrate 1 mg. Therefore, Activelle contains much less estrogen than Seasonique.
References: 1. http://www.pbm.va.gov/clinicalguidance/drugclassreviews/HormoneTherapyCombinedEstrogenProgestinAbbreviatedDrugClassReview.pdf
2. CTC - Menopause
3. https://pubchem.ncbi.nlm.nih.gov/compound/154274#section=Top
4. CTC - Contraception

Jun. 20, 2017How should a patient taper off triamcinolone 40mg/month for 2 years? details
 

Medical Problems: Originally was told the triamcinolone was intralesional. After calling back with response, was told that it was IM.
Response: An IM dose of 40-80 mg triamcinolone is expected to suppress HPA for 2-4 weeks.(10) Asthma patients who were given triamcinolone 80 mg IM q4weeks in a study were all found to develop adrenal suppression after 24 weeks' treatment. (12) Therefore, while it is still debatable that tapering is required, it seems reasonable to taper to err on the side of caution. No tapering strategies are available for this situation. They could consider reducing the dose by 10 mg q4weeks. If the patient complains of fatigue, weakness, muscle pain or has disease flare, the taper should go slower.(14)
References: 1. Micromedex Drug Consult - Comparative Dosage Table: Corticosteroids (Selected) Properties and Potencies
2. Canadian Pharmacist's Letter 2010; 26(5):260507
3. UTD - Intralesional injection
4. http://www.dermnetnz.org/topics/intralesional-steroid-injection/
5. eCPS
6. UTD - Clinical manifestations of adrenal insufficiency in adults
7. UTD - Glucocorticoid withdrawal
8. UTD _ Pharmacologic use of glucocorticoids
9. http://www.aafp.org/afp/2009/0215/p297.html
10. https://www.drugs.com/monograph/triamcinolone.html
11. http://www.nhsggc.org.uk/media/230935/Triamcinolone%20in%20adults%20Difficult%20Asthma%20Advice%20Note%20June%2013_with_Header.pdf
12. http://www.jaad.org/article/S0190-9622(06)00210-6/pdf
13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1020562/pdf/thorax00239-0040.pdf
14. GeriRxFiles
*nothing for intralesional absorption: Micromedex

Jun. 20, 2017What birth control should be used on a patient on Visanne? details
 

Response: There were no interactions flagged between dienogest and hormonal contraceptives (2,3); however, preferably estrogen is avoided as it can fuel the endometrial growth.(4) Dienogest does inhibit ovulation at 2 mg daily(5); however, it has not been developed as a contraceptive (and therefore data on pregnancy rates are not available). Women should use non-hormonal contraceptives(5), which would include copper IUDs and barrier methods. In endometriosis, the advantages of copper IUDs generally outweigh the potential or known risks.(7,8)
References: 1. RxTx - eCPS
2. Stockley's
3. Lexicomp
4. Canadian Pharmacist's Letter 2011; 27(12):271228
5. Schindler AE. Dienogest in long-term treatment of endometriosis.Int J Womens Health. 2011;3:175-84. doi: 10.2147/IJWH.S5633. Epub 2011 Jul 6. PMID 21792339
6. Rxtx - CTC - Contraception
7.https://www.cdc.gov/reproductivehealth/contraception/pdf/summary-chart-us-medical-eligibility-criteria_508tagged.pdf
8. http://apps.who.int/iris/bitstream/10665/173585/1/9789241549257_eng.pdf?ua=1

Jun. 20, 2017Patient was started on Gardasil 4 and had doses at 0 and 2 months. It is now d/c and now is only available as Gardasil 9. Do you have information about switching between the two? details
 

Patient Sex: M
Response: It is acceptable to finish the series with Gardasil 9.(1,2) This will provide protection against the strains common to the 4-valent and 9-valent vaccines (6, 11, 16, 18).(1) However, the patient cannot expect immunity against the 5 strains unique to the 9-valent unless he gets a full 3-dose course.
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-9-human-papillomavirus-vaccine.html
2. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm

Jun. 20, 2017How much calcium is in rosuvastatin calcium? details
 

Medication History: Rosuvastatin 10 mg PO OD
Response: In one 10mg rosuvastatin tablet, there is 0.400 mg of calcium. (1,2)
References: 1. Martindale 2014
Brayfield A, editor. Matindale: The Complete Drug Reference 38th Edition. United Kingdom: Pharmaceutical Press; 2014. p.1488.
2. P Table Website
Periodic Table. Http://www.ptable.com/ (accessed June 21, 2017).

Jun. 20, 2017Any issues combining rosuvastatin and gemfibrozil? details
 

Patient Sex: M
Medical Problems: T2DM
hypertriglyceri 6.49
LDL - couldn't determine
compliant as per report
Medication History: rosuvastatin 20 mg
Response: Unlike most statins, there has been no documented interaction between rosuvastatin and the fibrates, though there is still an increased risk of myopathy that will need to be monitored.(1) Caller does understand that the fibrates do not improve CV outcomes (2,3) but wants to try regardless. Suggested to use fenofibrate as it is associated with fewer interactions in general than gemfibrozil.(4,5)
References: 1. eCPS
2. http://www.onlinecjc.ca/article/S0828-282X(16)30732-2/pdf
3. http://www.cfp.ca/content/61/10/857
4. Stockley's
5. Lexicomp

Jun. 20, 2017What is the best method to administer phenytoin in relation to nasogastric feeding? details
 

Patient Age: 60
Patient Sex: F
Response: Feeds need to be held 2 hours pre and post phenytoin. There are two options:

1. Continue with the suspension. Dilute the volume 2-3 times with sterile water. Flush the tube with 20 ml sterile water before and after administration (1). Depending on the duration of the feeds, it is possible the phenytoin could be administered between 9-10 am, 2-5 pm, and 9pm or later.

2. Switch to phenytoin capsules, which can be dosed once daily (2). Generally liquids are preferred to solid dosage forms for feeding tube administration; however, in the case of phenytoin suspension which requires the feed holds and three times daily dosing, capsules have been recommended.(1) Open the capsules and make a slurry with sterile water. (1) Flush the tube with 20 ml sterile water before and after administration. (1) The switch from suspension to capsules is not 1:1. Each phenytoin capsules contains 100 mg phenytoin sodium, equivalent to 92 mg phenytoin acid. The suspension is labelled as free acid such that each 5 ml contains 125 mg phenytoin. (2) As such, the patient technically should be converted to 163 mg (160 mg) phenytoin. Certainly levels should be monitored.
References: 1. Alt Routes of Admin
2. RxTx - CPhA phenytoin monograph

Jun. 21, 2017We're seeing vyvanse being used for anorexia (binge-purge subtype) -- what is the evidence (safety/efficacy)? details
 

Response: 1. Evidence exists for using lisdexamphetamine in Bulemia or Binge-eating-disorder (1-4), but no evidence for using it in anorexia binge-purge subtype, though it is an area of interest (1,4). Anorexia with binge-purge is distinct from binge eating disorder (5), and there is the risk of appetite suppression and worsening of a person's anorexia if a stimulant is used. The most recent review (1), states:

"The finding of ADHD symptoms in [Anorexia Binge-purge] is as high as in [Bulemia] evoke the question if it is possible to try stimulant medication also in this group, if proven effective for [Bulemia]. However the risk due to appetite suppression in an underweight patient must be taken into consideration. Another possible approach for deepened understanding could be a longitudinal study to investigate how treatment for [eating disorders] interacts with ADHD symptoms and vice versa."

2. In summary, use of a stimulant this way is highly experimental and should only be done under close monitoring and after traditional treatments have failed.
References: 1. https://bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-016-1093-1
2.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4777329/
3. http://annals.org/aim/article/2531704/binge-eating-disorder-adults-systematic-review-meta-analysis
4. McElroy, S.L., Guerdjikova, A.I., Mori, N. et al. Curr Psychiatry Rep (2015) 17: 35. doi:10.1007/s11920-015-0573-1
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793109/
6. Medline literature search: (anorexia (all sub-types)) AND (stimulants OR amphetamines OR lisdexamphetamine OR methylphenidate)

Jun. 22, 2017Should patients be switched to a different oral contraceptive when they have been taking the same one for several years? Concern about effect on fertility or on the other hand, reduced effectiveness in preventing pregnancy. details
 

Patient Age: 24
Patient Sex: F
Medication History: oral contraceptive
Response: There is no evidence that long-term use of oral contraceptives delays or decreases the chances of pregnancy after stopping the pill.(1)(2) Oral contraceptives do not lose their effectiveness with long-term use - switching to a different product is not necessary if the patient is having no problems with the product she is currently using.(3)
References: 1. UpToDate - Risks and side effects associated with estrogen-progestin contraceptives
2. Prolonged use of oral contraception before a planned pregnancy is associated with a decreased risk of delayed conception. Hum Reprod (2002) 17 (10): 2754-2761.
3. How long can I safely take birth control pills? http://www.mayoclinic.org/healthy-lifestyle/birth-control/expert-answers/birth-control-pills/faq-20058110

Jun. 26, 2017Formula for a vancomycin suspension (200mg TID for 10 days desired) to use in a enteral tube feed? details
 

Medical Problems: 200mg TID for 10 days

C.Diff
Patient has a tube feed
Response: Here are the methods you could dose vancomycin for this patient.

1. Reconstitute the vancomycin for injection with sterile water for injection. This yields a concentration of 50mg/ml, so your patient’s dose would be 4ml TID for 10 days. Since they need 6 grams total to complete their course of therapy, based on what’s available you would have to order a case of 10x1g vials (~$650). Each 1g vial is reconstituted with 20ml of sterile water for injection and would have a shelf life of 24h once reconstituted. Even with NG tube administration, it would still be recommended to further dilute each dose in 15-30ml of water prior to administration to make it more palatable.

2. Same as above, but you could make a more palatable and stable compound with a 1:1 ora-sweet:water mixture. The compound would look like this:

Vancomycin oral solution 6 grams in 240ml (25mg/ml) from reconstituted IV vancomycin

1. Prepare a vehicle of 60ml ora-sweet : 60ml purified (distilled) water.
2. Reconstitute six 1g vials of vancomycin with 20ml of sterile water for injection each (120ml water total)
3. Add the reconstituted vancomycin to the vehicle

Shelf-life: Stable for 26 days room temperature, or 75 days refrigerated

3. Alternatively, using the capsules to make an oral solution may be cheaper (could order three JAMP-Vancomycin 125mg caps, 20 caps per pack, $330 total). I could not find any official formulas for this method, but vancomycin is highly soluble in water, so the following method should work:

Vancomycin oral solution 6 grams in 120ml (50mg/ml) from commercial capsules

1. Empty contents of 48 vancomycin 125mg capsules into a mortar. Dissolve with approximately 60ml of distilled water.
2. Add 60mls of ora-sweet to yield 120ml of product

Shelf-life: Stable for 26 days room temperature, or 75 days refrigerated
References: 1. http://www.salfordccg.nhs.uk/download.cfm?doc=docm93jijm4n3351.pdf&ver=3547
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999368/
3. IJPC, Jan/Feb 2011, pg 73
4. http://www.iwk.nshealth.ca/sites/default/files/compounding-formulas/vancomycin%2025%20mg.pdf?m=1

Jun. 30, 2017I have a 19 yo client who is diagnosed with cone cell dystrophy. She was told to take Omega 3 and Vitalux, but we do not know the dose. details
 

Patient Age: 19
Patient Sex: F
Medical Problems: cone cell dystrophy
Response: Rod-cone and cone-rod dystrophies (the difference lies in the first type of cells to degenerate) are heritable retinal diseases more commonly referred to as retinitis pigmentosa (RP).(1,9) Very little in terms of treatment is available.(7)
Nutritional supplementation has shown promise in some observational trials, but this has not panned out in RCTs (7,8) such that they can’t be recommended based on effectiveness. DHA has been studied in doses of 400 mg daily for 4 years(3) as well as 1200 mg daily for 2 years.(2) Lutein has been studied at doses between 10 and 30 mg daily.(4,5) Vitamin A has been included in some studies at a dose of 15 000 IU daily(1,5) though based on the toxicity of Vitamin A and lack of demonstrated effectiveness for RP, it is not recommended.(7) That said, none of the Vitalux products contain Vitamin A (some contain beta-carotene).(10)
References: 1. Sahel JA, Marazova K, Audo I. Clinical characteristics and current therapies for inherited retinal degenerations.Cold Spring Harb Perspect Med. 2014 Oct 16;5(2):a017111. doi: 10.1101/cshperspect.a017111. Review. PMID: 25324231
2. Berson EL, Rosner B, Sandberg MA, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004 Sep;122(9):1306-14. PMID 15364709
3. Hoffman DR, Locke KG, Wheaton DH, et al. A randomized, placebo-controlled clinical trial of docosahexaenoic acid supplementation for X-linked retinitis pigmentosa. Am J Ophthalmol. 2004 Apr;137(4):704-18. PMID 15059710
4. Bahrami H1, Melia M, Dagnelie G. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial [NCT00029289]. BMC Ophthalmol. 2006 Jun 7;6:23. PMID 16759390
5. Berson EL, Rosner B, Sandberg MA, et al. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol. 2010 Apr;128(4):403-11. doi: 10.1001/archophthalmol.2010.32. PMID 20385935
6. Aleman TS, Duncan JL, Bieber ML, et al. Macular pigment and lutein supplementation in retinitis pigmentosa and Usher syndrome. Invest Ophthalmol Vis Sci. 2001 Jul;42(8):1873-81. PMID 11431456
7. UTD - Retinitis pigmentosa: Treatment
8. Natural Medicines
9. Dynamed - Retinitis pigmentosa
10. http://www.vitaluxvitamin.ca/en/vitalux-family-of-products/time-release.shtml

Jul. 4, 2017Are there any interactions between methotrexate (MTX) and Mezavant which I am wanting to initiate for ulcerative colitis? I have never had difficulties with concurrent use previously but am now being told that there is an interaction? I'm wondering if the person expressing concerns is confusing Mezavant with NSAIDS. What is the bottom line regarding concurrent use? details
 

Patient Age: 78
Patient Sex: M
Medical Problems: Rheumatoid arthritis
ulcerative colitis

72.5 kg
Medication History: methotrexate 17.5 mg weekly
rabeprazole 20 mg daily
Response: Regarding the combination of methotrexate and 5-ASA, I looked in my usual drug interaction resources(1-4) and only one(3) indicated an interaction. The mechanism of the potential interaction is additive nephrotoxicity.(3) However, while the discussion of the interaction was general (nephrotoxic drugs were included), for methotrexate it specifies high intravenous doses.(3) As such, this interaction does not apply to your case. Concerns could be alleviated by ordering a renal panel.
References: 1. Stockley's
2. Lexicomp
3. drugs.com
4. RxTx, Mezavant

Jul. 4, 2017Imuran (azathiprine) is considered a non-antineoplastic hazardous drug so we glove when handling it and tell patients to wash their hands after taking. A nurse has told a family member they should have been gloving and gowning when dealing with biological fluids of the patient taking this. (Apparently the patient sometimes has urinary incontinence that family members clean up.) details
 

Medical Problems: Myasthenia gravis
Medication History: Mestinon SR 180 mg OD. Regular 120 mg QID
Azathioprine 200 mg OD
Response: Azathioprine is on the hazardous drug list (Group 2 = non-antineoplastic).(2) According to NIOSH and ASHP guidelines, caregivers handling biological waste of patients taking hazardous drugs should double glove, gown, and use eye/face protection (if chance of splashing) if the drug has been taken in the previous 48 hours.(2,3)
References: 1. Lexicomp
2. Safe Handling of Hazardous Drugs (Lexi-Drugs)
3. https://www.osha.gov/SLTC/hazardousdrugs/controlling_occex_hazardousdrugs.html

Jul. 4, 2017Dentist recommended glycerin in a glass of water for dry mouth. I presume it's safe to put in mouth? details
 

Response: While therapeutic doses of glycerin can cause water to move from the extravascular spaces to the plasma (and therefore is used for conditions such as cerebral edema), a therapeutic dose is 1 to 1.8 g/kg given as a 50% solution,(2) far higher than a few drops in 250 ml water. Biotene Mouth spray contains glycerin(3) and has been used as a demulcent. There is no evidence a low concentration of glycerin will be effective, but it won't be harmful and if less expensive than products marketed for dry mouth, seems reasonable to try.
A few drops (e.g. 3) in 250 ml water = 0.06%
References: 1. RxTx - CTMA Dry Mouth
2. Martindale's
3. RxTx - CPMA - Dry Mouth

Jul. 4, 2017Is Qvar safe for a 5 month old? Everything I see says 5 years and up. details
 

Medication History: salbutamol, prednisolone (in past)
Response: No asthma products are labelled by Health Canada for children younger than 1 year and at that, fluticasone is the only one labelled for children under 4 years.(1) However, a step-wise approach is used for infants as for other patients (4,5) and following trial of PRN short-acting bronchodilator, low dose inhaled corticosteroid is added.(5) As such, it is the approximate equivalent dosing that is important. A daily dose of 100 mcg Qvar is considered low.(4) This child has been prescribed 50 mcg daily, which is appropriate.
References: 1. RxTx - CTC- Asthma in Infants and Children
2. BNF Children
3. Cdn Thoracic Society 2012 Guidelines - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3373283/pdf/crj19127.pdf
4. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Asthma.pdf
5. UTD - An overview of asthma management Figure: Stepwise approach for managing asthma in children 0 to 4 years of age

Jul. 4, 2017Patient switching from Concerta 27 mg to Vyvanse 30 mg. He had his last Concerta dose 48 hours ago. Is it okay for him to start Vyvanse today? details
 

Response: When switching from methylphenidate to an amphetamine-based agent, it is recommended to stop the methylphenidate and begin the second at the starting dose. The starting dose of Vyvanse is 20-30 mg.(1) It is appropriate to start Vyvanse at this time.
References: 1. https://www.caddra.ca/pdfs/caddraGuidelines2011Chapter07.pdf

Jul. 4, 2017MD has ordered Humalog 10 units by IV. We usually give regular insulin IV; can Humalog be given IV? details
 

Medical Problems: 19.3
Medication History: Humulin R
Response: Insulin lispro (Humalog) can be administered intravenously (1,2) as a solution diluted to 0.1 to 1 unit/ml in normal saline as continuous infusion.(2)
References: 1. eCPS
2. Ottawa Hospital Parenteral Drug Therapy Manual
*SK IV Manual (no monograph for lispro)

Jul. 5, 2017A patient has been on metoclopramide. Due to an observed mouth tremor, one of our pharmacists recommended a dose reduction from 10 mg TID to 5 mg TID. If the metoclopramide is responsible for the twitch, how long will it take to resolve? details
 

Medical Problems: CrCl: 27 ml/min
COPD - uses lots of Combivent and long acting beta agonists
Response: The incidence of tardive dyskinesia (TD) has been estimated to be 20% in patients taking the drug for 3 months or longer. The risk increases with age and is more likely in women. The TD is described as an involuntary movements of the face, tongue, or extremities. It is often irreversible with drug discontinuation, though may remit or partially improve within weeks to months of discontination in some patients. While patients who will recover cannot be predicted, it is thought advanced age, higher doses, and longer exposure duration increase the risk of the disorder being irreversible.(2)
References: 1. RxTx - CPhA metoclopramide monograph
2. https://www.fda.gov/downloads/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm111378.pdf

Jul. 5, 2017Has there been anything published re: Pradaxa storage in compliance packaging since the one you referred to in your 2015 article? details
 

Response: No new evidence has been published since the study (1) on which the medSask article(2) is based.(3,4)
References: 1. Wang EHZ, Bolt JL, Decarie D, et al. Stability of dabigatran etexilate in manufacturer’s blister pack, unit-dose packaging, and community pharmacy blister pack. CJHP 2015; 68(1): 16-21
2. https://medsask.usask.ca/documents/hot-topics/Pradaxa_Update.pdf
3. PubMed: "dabigatran stability"; "dabigatran storage"; "dabigatran compliance"
4. Scopus: "dabigatran stability"; "dabigatran storage"; "dabigatran compliance"

Jul. 5, 2017Our patient has been using Pepto Bismol twice daily on a fairly regular basis. Given she also takes celecoxib and rivaroxaban, I want to recommend the Pepto be switched to Gaviscon. However, Lexicomp flags an interaction between Gaviscon and Vitamin D saying Vit D will increase absorption of aluminum. Is this a clinically significant interaction? details
 

Medical Problems: Renal function?
Medication History: celecoxib, rivaroxaban, PPI started, others
Vitamin D 2000 IU daily
Response: Vitamin D does increase absorption of aluminum, magnesium, calcium and phosphate.(1,5) Antacids contain either one of these minerals, sodium bicarbonate (likely also not an option), or are H2-receptor antagonists.(2) If liquid is required, options include aluminum, magnesium and/or calcium.(2) Considering magnesium and calcium can be easily monitored, these products would be preferred to aluminum-containing products. If liquid is not required, an H2-receptor antagonist would be preferable.
References: 1. Lexicomp
2. RxTx CMPA - Gastrointestinal Products: Antacid, Antiflatulent and Antireflux
3. RxTx CPhA Mg Monograph
4. RxTx CPhA Vit D monograph
5. Stockley's

Jul. 5, 2017I am trying to find some information regarding a phenobarbital tapering schedule for my patient with seizure disorder. Prior to now, her last seizure was in 7 months ago. She is still taking phenobarbital 15mg TID. But her doctor wishes to taper her off phenobarb due to potential toxicity/harm. She has now been tapered up to a therapeutic dose of divalproex EC (500mg BID). Her other medications include clobazam 10mg bid, carbamazepine 400mg BID and 200mg HS. She is also taking rosuvastatin 5mg for hypercholesterolemia, and VitD, B12, and calcium. I have only found one case report on a protocol for tapering 10% of the total phenobarb dose q 2 weeks… but this doesn't appear to be supported by any evidence. details
 

Medical Problems: seizure disorder - last seizure Dec 2016
Medication History: VPA 500 mg BID, clobazam 10mg bid, carbamazepine 400mg BID and 200mg HS
rosuvastatin 5mg, VitD, B12, and calcium
Response: Tapering protocols are more of an art than a science. Recently, Geri-RxFiles and medstopper.com have become available to provide general guidance on tapering. Both of these resources recommend phenobarbital (when used for seizure) be reduced by 10-25% every 4 weeks. This range is then applied to the individual patient. Considering the number of anticonvulsants required for your patient, I would lean toward a slower taper (10% each dose reduction); however, you and the physician will need to factor in the potential harm being experienced by this patient, which may give reason to hasten the schedule. The fact she has a replacement anticonvulsant at therapeutic dose on board certainly reduces concern of inducing a seizure with discontinuation.
References: 1. GeriRxFiles
2. medstopper.com
3. Lexicomp
4. Geurian K, Burns I. Detailed description of a successful outpatient taper of phenobarbital therapy. Arch Fam Med. 1994 May;3(5):458-60. PMID: 8032508

Jul. 5, 2017Patient was positive for chlamydia and gonorrhea a week ago. She was given ceftriaxone 1g IV on that day. Would this treat the GC or do we need to start over with 250 mg IM again? (She also received one dose of 100 mg doxycycline so she will be receiving treatment for chlamydia) details
 

Response: The client should be treated with ceftriaxone IM (preferred) or cefixime + azithromycin (preferred) or doxycycline today. (4) This is based on the fact genitourinal tissue concentrations following ceftriaxone 1g IV are not available (5) and more so on the recent guidelines released by Health Canada iterating combination therapy for gonorrhea with a cephalopsorin and macrolide should ideally be administered concurrently, that there is insufficient evidence to recommend what (if) lapse of time can be sustained to achieve the same benefit as concurrent administration, and that if the drugs are not administered concurrently, there may be reduced effectiveness.(2)
References: 1. #318 5/6/2016
2. Jade/Dz Files/1. Infectious Disease/STI/Cdn STI Guideline Updates_Apr2017
3. DrugDex
4. http://www.phac-aspc.gc.ca/std-mts/sti-its/cgsti-ldcits/section-5-6-eng.php#toc361210465
5. Fraschini F, Zoncada F, Scaglione F, et al. Distribution of ceftriaxone in the tissues of the female genital system. Int J Clin Pharmacol Res. 1987;7(6):499-502. PMID: 3440640

Jul. 6, 2017Patient prescribed Lomotil but has codeine and sulfa allergy. Is there cross-sensitivity? details
 

Medical Problems: codeine and sulfa allergy: hives and stomach pains for both
Medication History: loperamide does not sit well with her
Response: Because the patient experienced hives (and not other rash or severe skin reaction), this is more likely a pseudoallergic reaction caused by histamine release in which case using an opioid of a different class is reasonable.(1) Codeine is in the morphine group, whereas diphenoxylate is in the synthetic class of phenylpiperidine.(3)
References: 1.Canadian Pharmacist's Letter; February 2006; Vol: 22
2. Lexicomp - Diphenoxylate and Atropine (Drug Allergy and Idiosyncratic Reactions)
3. Lexicomp - AHFS DI

Jul. 6, 2017Can you send me options for treatment of cold sores in children. details
 

Response: Treatment of primary herpetic gingivostomatitis in children is well established:
- Supportive care with fluids and analgecs(1,4)
- In the event of severe presentation (unable to drink or significant pain) and within 48-72 hours of symptom onset, acyclovir is an optn(1,4) Several dosing regimens are available:
- 40-60 mg/kg/day divided into 4-5 doses for 5-7 day(1)
- 15 mg/kg 5x per day for 5-7 day(3,4)
- A British reference also lists valacyclovir 500 mg BID x 5 days for children 2-17 year(2)
*Note that primary herpetic gingivostomatitis is quite different from recurrent lesions as it is often associated with a prodrome that may include fever, anorexia, irritability, malaise, sleeplessness, and headache. (4)

No information is available for treatment of recurrent herpes simplex in immunocompetent children. I suspect this is because recurrent herpes simplex is not common in immunocompetent children so the diagnosis should possibly be questioned and/or the child investigated for a suppressed immune system. The British reference does not differentiate between treatment of primary herpes simplex treatment and recurrent herpes simplex treatment. It recommends acyclovir at the following doses:
- Infants 1 to 23 months: 100 mg 5x per day for 5 das(2)
- Children 2-17 years: 200 mg 5x per day for 5 dys (2)
References: 1. Bugs and Drugs app
2. BNF Children 2016-17
3. RxTx CTC Herpesvirus Infections
4. UTD - Keels M, Herpetic gingivostomatitis in young children

Jul. 6, 2017When bridging warfarin, do you use a prophylactic or therapeutic dose of the LMWH? I see your document provides doses of enoxaparin and dalteparin but this MD wants to use tinzaparin. details
 

Patient Sex: F
Medical Problems: Multiple PE's -
Normal renal function
103 kg
colonoscopy - possiblity of polypectomy
Response: The LMWH dose should be therapeutic,(1,2,3, 5) which for tinzaparin is 175 U/kg or ~ 18 000 units for this patient.(4)
References: 1. http://www.thrombosiscanada.ca/guides/pdfs/Warfarin_perioperative_management.pdf
2. http://medsask.usask.ca/documents/newsletters/33.2%20Periprocedural%20Antithrombotics.pdf
3. Canadian Pharmacist's Letter 2015; 31(8):310836
4. eCPS
5. Nazha B1, Spyropoulos AC2. The BRIDGE trial: What the hospitalist should know. J Hosp Med. 2016 Sep;11(9):652-7. doi: 10.1002/jhm.2594. Epub 2016 Apr 21. PMID 27098835

Jul. 6, 2017What is the safety of eletriptan in pregnancy? Not pregnant yet but thinking about it. details
 

Medical Problems: migraine
Medication History: eletriptan - first triptan tried
Response: When treating migraines in pregnancy, acetaminophen +/- caffeine +/- metoclopramide is first line.(2,3) If this is ineffective, intermittent doses of NSAIDs can be tried next, if the woman is not in the third trimester.(1,2) If triptans are required, sumatriptan would be the drug of choice simply owing to greater data;(2,3,4) it does not appear to increase the risk of negative pregnancy outcomes though the possibliity of increasing preterm birth cannot be ruled out.(5)
References: 1. RxTx- CTC Headaches in Adults
2. UTD - Headache in pregnant and postpartum women
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Peri-Pregnancy-DrugTx.pdf
4. http://www.motherisk.org/prof/updatesDetail.jsp?content_id=928
5. Briggs

Jul. 6, 2017I want to switch a patient from Humulin R to Humalog. Is the dosing 1:1? details
 

Response: Yes. (1,2)
References: 1. eCPS
2. Canadian Pharmacist's Letter 2015; 31(11):311128

Jul. 6, 2017Is T3 (triodothyronine) available in Canada? details
 

Response: Yes, it is available as Cytomel 5 mcg and 25 mcg tablets. (1)
References: 1. PharmaClik

Jul. 6, 2017I have a patient who wants to stop gabapentin. He has been on it for several months at 600 mg TID. What would be an appropriate taper? details
 

Response: A reduction of 25% of original dose weekly is reasonable with assessment of withdrawal symptoms and re-emergence of neuropathy, which may dictate a slower taper.(1,2)
References: 1. GeriRxFiles
2. medstopper.com

Jul. 7, 2017Can amoxicillin capsules be opened and sprinkled on soft food? details
 

Response: While there is no information specific to this because the suspenion is available,(1,2) there is no reason the capsule can't be opened.(3,4)
References: 1. AHS Alt ROA
2. Handbook of Drug Administration thru Enteral Feeding Tube
3. http://www.ismp.org/tools/donotcrush.pdf
4. Canadian Pharmacist's Letter 2015; 22(1):310126

Jul. 7, 2017Vitamin K injection - 10 mg/ml. Can we give it orally? details
 

Response: Yes. Tablets are only available through Special Access so the injectable is usually the dosage form used for oral administration.(1)
References: 1. RxTx - CPhA Vitamin K monograph

Jul. 7, 2017Is divalproex a drug of abuse? What about Dilantin? details
 

Response: A search of the literature as well as a website for posting experiences of recreational use of licit and illicit drugs yielded nothing of note for valproic acid aside from some accounts of it possibly reducing (1,2) or enhancing (3) the effect of other drugs; as well as one of an adverse reaction with use of a combination of drugs, including VPA.(4) No information was found in the published literature.
Several accounts of phenytoin - most often in people who had been prescribed it for seizure activity - are described on the website with the most common effect described being enhanced concentration and memory (6,7) as well as better dreams.(5) There were also accounts of adverse effects. One published case of recreational use of phenytoin was found; however, this person did not take it intentionally; he thought he was buying a street opioid but was given phenytoin. Based on rat studies, the author speculates "cannabis may produce effects similar to a cocaine high, especially when taken with other drugs such as phenytoin".(9)
A case was reported of someone who opened the contents of his girlfriend's phenytoin and mixed with the crack cocaine he regularly smoked. He described an "unbelievable high" but also experienced nausea, ataxia, and dysarthria.(11) Another NYC hospital reports on five cases in which crack cocaine was mixed intentionally with phenytoin before smoking. The authors note these patients disclosed that mixing phenytoin with crack cocaine was becoming common street practice.(12)
A review article of misuse of anticonvulsants includes a section on recreational use but only includes gabapentin, pregabalin and clonazepam.(10)
References: 1. https://www.erowid.org/experiences/exp.php?ID=84473
2. https://www.erowid.org/experiences/exp.php?ID=27915
3. https://www.erowid.org/experiences/exp.php?ID=21490
4. https://www.erowid.org/experiences/exp.php?ID=60867
5. http://www.drugcocktails.ca/medications/valproic-acid-divalproex-valproate
6. https://www.erowid.org/experiences/exp.php?ID=70148
7. https://www.erowid.org/experiences/exp.php?ID=18668
8. drugcocktails.ca
9. Jessen K. Recreational use of phenytoin, marijuana, and alcohol: a case report. Neurology 2004. 62(12): 2330
10. Piskorska B, Miziak B, Czuczwar SJ, Borowicz KK. Safety issues around misuse of antiepileptics. Expert Opin Drug Saf. 2013 Sep;12(5):647-57. doi: 10.1517/14740338.2013.796363. Epub 2013 May 4. Review. PMID: 23642151
11. Koppel B, Daras M, Samkoff L. Phenytoin neurotoxicity from illicit use. Neurology 1995;45:198. PMID: 7824121
12. Katz A, Hoffman R, Silverman R. Phenytoin toxicity from smoking crack cocaine adulterated with phenytoin. Ann Emerg Med 1993;22:1485– 1487. PMID 8363126

Jul. 10, 2017I have a patient wondering what kind of nutrient/ vitamin depletions he might get being on his medications? I haven't been able to find too much information on this. Current meds are Coversyl 4mg OD, Metoprolol 25mg OD, Xarelto 20mg OD details
 

Patient Age: 72
Patient Sex: M
Medication History: Coversyl 4mg OD, Metoprolol 25mg OD, Xarelto 20mg OD
Response: No nutritional deficiencies were identified for rivaroxaban or metoprolol (1,3,4). Perindopril may be associated with hyponatremia(3,4).
References: 1. http://medsask.usask.ca/documents/newsletters/34.4%20Drug-Induced%20Nutrient%20Deficiencies.pdf
2. Food-Medication interactions 16th Ed.
3. RxTx -eCPS
4. Micromedex
*PubMed

Jul. 10, 2017Patient would like me to give him his testosterone shot (Delatestryl). As far as I can tell it has to be administered in the gluteal muscle. Is that true? (If so, will refer to physician to inject.) details
 

Response: The Delatestryl monograph indicates administration into the gluteal muscle with no mention of other sites(1); this is also the only site mentioned in an American Nursing reference.(3) A tolerability study in healthy volunteers compared injection of testosterone enanthate in castor oil via gluteal, thigh and deltoid sites; the gluteal site was less prone to bleeding but was painful more often than deltoid or thigh injection sites.(4) It should be noted the formulation available in Canada uses sesame, not castor, oil.(1) Guidelines for Phamacists by the Saskatchewan College of Pharmacy Professionals state the route of administration should follow established protocols, if available.(5)
References: 1. PM from DPD
2. Lexicomp
3. Nursing Reference Center Plus: Testosterone enanthate By: Vallerand AH, Sanoski CA, Davis's Drug Guide for Nurses, January 1, 2017
4. Hum Reprod. 1995 Apr;10(4):862-5. Tolerability of intramuscular injections of testosterone ester in oil vehicle. Mackey MA1, Conway AJ, Handelsman DJ. PMID 7650133
5. http://saskpharm.ca/uploaded/web/refmanual/REF_Injection_Admin_Gdlns_Current.pdf
*RxFiles, Search of Nursing Reference Center Plus "testosterone [enanthate] deltoid"

Jul. 11, 2017Are there any guidelines for switching from gabapentin to topiramate? details
 

Medical Problems: neuropathy
Medication History: currently on gabapentin 600 mg PO TID
Response: The gabapentin should be tapered; 25% reduction per week is a good place to start.(3,4) Aside from additive CNS (1), there are no interactions between gabapentin and topiramate(2) so the topiramate can be titrated up (starting at 25 mg HS)(5) as the gabapentin is tapered.
References: 1. Lexicomp
2. Stockley's
3. GeriRxFiles
4. medstopper.com
5. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Pain-Chronic-NonCa.pdf

Jul. 11, 2017Can naltrexone 50 mg be split? It's film-coated. details
 

Response: Naltrexone is not on the do not crush list(1); it is not a narrow therapeutic index drug, is not a modified release product, does not contain more than one active ingredient and is not friable. Therefore, there is no reason it can't be split.(2)
References: 1. http://www.ismp.org/tools/donotcrush.pdf
2. Canadian Pharmacist's Letter 2012; 19(7):280737

Jul. 13, 2017How long should Xarelto be held before colonoscopy? details
 

Patient Sex: M
Medical Problems: eGFR unknown but 'everything is good'
going for colonoscopy
Response: The time for discontinuation depends on the bleed risk.(1,2) For rivaroxaban, the same discontinuation time applies to all degrees of renal function and all CV risk (CHADS2 score 1-6)(2):
Low bleed risk = colonoscopy only - do not discontinue (2)
Intermediate bleed risk = colonoscopy with biopsy - discontinue 2 days before (i.e. skip at least 1 dose; do not take a dose for at least 24 hours before procedure) (1,2)
High bleed risk = colonoscopy with polypectomy - discontinue 3 days before (i.e. skip 2 doses; do not take a dose for at least 48 hours before procedure) (1,2)
Polpectomies are generally performed during diagnostic procedures (i.e. it is possible they will need to perform a polypectomy in this patient during this scope).(3) Ideally, the surgeon would be contacted as to his/her expectation of requiring polypectomy or even biopsy. Without this information, it seems reasonable to go in the middle - discontinue the rivaroxaban at least 24 hours in advance of procedure in case a biopsy is required. The surgeon should be made aware of this in case polypectomy is considered during scope.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/CLOT-Rivaroxaban-Checklist-Final-CPP.pdf
2. http://thrombosiscanada.ca/?page_id=502&calc=perioperativeAnticoagulantAlgorithm
3. UTD - Overview of colonoscopy in adults

Jul. 13, 2017We have a new patient from BC. She takes methotrexate (MTX) 20 mg SC q1week for rheumatoid arthritis. She was supposed to get her MTX yesterday but we didn't have it in stock and so she won't get it until today. However, she was given her leucovorin calcium 5 mg yesterday. Should she get the MTX this week since she already had leucovorin? Does she need another dose of leucovorin calcium if she does get MTX this week? details
 

Medical Problems: RA
Medication History: MTX 20 mg SC q1week
leucovorin calcium 5 mg PO on day of MTX
Response: There is no information as to the best regimen for folate supplementation in low dose MTX regimens.(1) In the studies with low dose MTX, folinic acid was administered following the weekly MTX dose, either 4 hours post(5) or the following day.(4) The risk of dosing MTX after folinic acid is potentially reduced effectiveness of the MTX; however, this is theoretical and the patient will receive some, if not all, of the usual benefit of MTX. Therefore it is better to provide the dose this week than not at all. Again, on account of the variation of regimens with none known to be superior, there is no reason to provide another dose of leucovorin today.
Leucovorin calcium is costly; the acquisition cost is $7.50 per 5 mg tablet compared to folic acid, which is $0.43 per 5 mg tablet.(3) As the leucovorin is only covered by the SK government for patients with folate deficiency due to chronic use of TMP/SMX (2), this patient will not be covered for the leucovorin (unless private insurance). There is no evidence one of the folate supplements is superior to the other for the purposes of low dose MTX.(1) Therefore, there is no reason not to switch to the less costly folic acid 5 mg, which can be continued at the same dose regimen as the folinic acid.
References: 1. Shea B, Swinden MV, Tanjong Ghogomu E, Ortiz Z, Katchamart W, Rader T, Bombardier C, Wells GA, Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD000951. DOI: 10.1002/14651858.CD000951.pub2.
2. Drug Plan online formulary - http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
3. PharmaClik
4. Low-dose methotrexate with leucovorin (folinic acid) in the management of rheumatoid arthritis. Results of a multicenter randomized, double-blind, placebo-controlled trial.
Shiroky JB, Neville C, Esdaile JM, Choquette D, Zummer M, Hazeltine M, Bykerk V, Kanji M, St-Pierre A, Robidoux L, et al. Arthritis Rheum. 1993 Jun;36(6):795-803. PMID: 8507221
5. Administration of folinic acid after low dose methotrexate in patients with rheumatoid arthritis. Buckley LM, Vacek PM, Cooper SM. J Rheumatol. 1990 Sep;17(9):1158-61.
PMID: 2132565

Jul. 14, 2017I have a patient on Tylenol #3 and gabapentin trying to conceive. It looks like they are not preferred in pregnancy and gabapentin is teratogenic. Can you tell me where I can find information about what the effects are? I'm going to advise she discontinue and look for other pain modalities. How should the gabapentin be tapered? details
 

Medication History: gabapentin
Tylenol #3
Response: Gabapentin: Thirty women used gabapentin, one of whom delivered an infant with a major malformation: pyloric stenosis with bilateral fifth finger clinodactyly and prominent epicanthal folds (mother treated for seizures with monotherapy). Two of the 13 infants that were examined by a dysmorphologist had anticonvulsant facies (one monotherapy and the other combined with carbamazepine). In addition, two had neurologic abnormalities: failure to gaze up (sunsetting), opisthotonus, frontal bossing, medial flare of the eyebrows, and small for gestational age (mother treated for depression with gabapentin, doxepin, clonazepam, nefazodone, and zolpidem); sunsetting and metopic ridge (mother treated for chronic fatigue and fibromyalgia with gabapentin, lorazepam, and fluoxetine). Although they were not conclusive, the findings suggested reason for concern with gabapentin, as well as the same phenotype that has been observed with older anticonvulsants.(1)
Codeine congenital defects that have been reported: (observed/expected) 74/76 cardiovascular defects, 14/13 oral clefts, 4/4 spina bifida, 25/22 polydactyly, 15/13 limb-reduction defects, and 14/18 hypospadias. Only with the total number of defects is there a suggestion of an association between codeine and congenital defects, but other factors, including the mother's disease, concurrent drug use, and chance, may be involved.(1)
Reducing the dose by 25% per week is a good starting place for a taper.(2,3)
References: 1. Briggs
2. GeriRxFiles
3. medstopper.com

Jul. 14, 2017We have a patient who is on atorvastatin 80 mg. He finds it quite large to take. Is he deriving any benefit from this dose? details
 

Patient Age: 91
Patient Sex: M
Medical Problems: MI and then CABG 6 yrs ago
not diabetic, non-smoker
treated HTN - usually ~145/60
TC = 3.04; HDL = 1.09; LDL 1.53
Medication History: Ezetrol 10 mg daily
atorvastatin 80 mg daily - having no adverse effects
Response: Based on ACC/AHA ASCVD risk calculator(1), patient's risk of an event is 42.3%. Because this is >20%, high-intensity statins are recommended.(2) High-intensity statin use reduces this risk 27.5%; low-moderate intensity statin use reduces the risk to to 31.7%. However, the calculator is only intended for adults up to age 80.(2) Consideration to reducing dose or discontinuing statins should be given when the risks outweigh benefits or when there is insufficient benefit to be of value to the patient - such as if he has severe physical or cognitive impairments or is in the last year of life.(3) Since the patient is older than the age of the patients in the trials (3) and he has expressed some displeasure of taking at least this dose so a discussion of the benefits with him is definitely warranted.
References: 1. http://chd.bestsciencemedicine.com/calc2.html
2. Simplified Lipid Guidelines - http://www.cfp.ca/content/61/10/857.full
3. Geri RxFiles, pg 4-C

Jul. 14, 2017My patient has been on Cymbalta (duloxetine) for about a month and I want to increase him to 80 mg. Should I go to 70 mg then 80 mg or just straight to 80 mg? details
 

Response: Cymbalta is only available as 30 mg and 60 mg delayed release capsules(1) so you will have to increase the dose to 90 mg daily. Note there is no evidence of additional benefit when increasing above 60 mg daily.(1)
References: 1. RxTx - eCPS - Cymbalta

Jul. 14, 2017A client is on ketorolac and Azarga (brinzolamide—timolol maleate) drops. The specialist told her she needs to wait 10 minutes, not 5 minutes between drops. Is there something new? details
 

Response: All consulted references suggest to wait 5 minutes between eye drops (1-3) and nothing was found in a literature search.(4)
References: 1. Lexicomp
2. RxTx - CTC Cataract Surgery Postoperative Care
3. RxTx - CTC Glaucoma
*PubMed "ophthalmic drop instillation"; "ophthalmic drop administration"

Jul. 14, 2017Patient is in her late 50's and is on HRT. She's spotting daily since she started about 6 months ago. Is this normal? Should there be any changs to her medication?Her current medications are Climara 100 mcg/ patch and Provera 2.5 mg details
 

Patient Sex: F
Medication History: Climara 100 mcg/ patch
Provera 2.5 mg
Response: 40% of women on a continuous hormone regimen have irregular bleeding/spotting during the first 3-6 months of use that may persist up to 12 months(1,2); this is more likely if the woman is less than 2 years past menopause(2). Women who continue to have bleeding after six months of therapy need to have evaluation of the endometrium: if proliferation is found, the progestin dose should be increased (to 5 mg daily); if atrophy is found the progestin dose should be reduced (since she’s already on the lowest dose, she could reduce the number of days per month she uses it to 21).(2)
References: 1. RxTx CTC - Menopause
2. SOGC - Menopause 2014

Jul. 14, 2017We have a specialist who has prescribed 1/4 of a nitroglycerin patch. Is this okay? If so, we have Mylan patch; can it be cut? details
 

Medical Problems: tendinitis
Response: There is evidence small pieces of nitroglycerin patches may help with pain and healing of tendinopathies.(1,4) The Mylan brand is a matrix patch so can be cut.(2,3)
Topical nitroglycerin patches effectively reduce pain associated with activities of daily living in patients with chronic tendinopathies.(4) Consider using one-quarter of a nitroglycerin 0.2 mg/h matrix patch (e.g., Nitro-Dur, Trinipatch) daily on the affected joint area, rotating the application site with each application. The most common side effect is headache, but patients may also experience skin rash, dizziness and hypotension. Use with caution in the elderly or patients taking antihypertensives, due to the increased risk of orthostatic hypotension. (1)
References: 1. RxTx - CTC - Sports Injuries
2. NOC database
3. Canadian Pharmacist's Letter 2017; 33(7):330733
4. 04 Jul 2012 RUMOUR vs Truth: Nitroglycerin patches can be used to treat tennis elbow.

Jul. 17, 2017We have a prescription for chorionic gonadotrophin 10 000 units vial but the doctor wants patient to mix with 5ml diluent rather than 10ml and inject 2.5 ml to get 5000 units. Is 5 ml diluent enough to dissolve properly? details
 

Medical Problems: put on file
Response: Volumes of diluent between 1 to 10 ml can be used to achieve different concentrations when reconstituting.(1,2) Adding 5 ml diluent and injecting 2.5 ml is specifically noted for a dose of 5000 units.(2)
References: 1. RxTx - eCPS - Pregnyl
2. Personal Message from DPD CHORIONIC GONADOTROPIN FOR INJECTION, USP from Fresenius Kabi Canada; DIN 02247459

Jul. 17, 2017MD wants info about heberprot-p75 Easyef; it's an epithelial growth factor for diabetic foot ulcer healing. He wants to use it in a patient and wanted some basic information? details
 

Response: This product is not available in Canada (3) nor is any other of several growth factors that have been researched for diabetic foot ulcers.(2)
References: 1. https://en.wikipedia.org/wiki/Nepidermin
2. Martí-Carvajal AJ, Gluud C, Nicola S, Simancas-Racines D, Reveiz L, Oliva P, Cedeño-Taborda J. Growth factors for treating diabetic foot ulcers. Cochrane Database of Systematic Reviews 2015, Issue 10. Art. No.: CD008548. DOI: 10.1002/14651858.CD008548.pub2.
3. Health Canada Drug Product Database

Jul. 17, 2017We received Mylan-verapamil SR 180 mg today. It has a different DIN from other stock we have. They are similar looking tablets but different markings. Are they interchangeable? Is there any difference between the two? 02210355 (former) 02450488 (received today). Markings: older ones Knoll - SR|180. Newer ones M|VM 2- other side blank. details
 

Response: The first DIN has been discontinued from the market.(1,4) The second DIN is bioequivalent to the first (though excipients differ somewhat)(4) and they are considered interchangeable in Saskatchewan.(2)
References: 1. Health Canada Drug Product Database
2. Sask Formularly online
3. http://ev.mylan.ca/Product.aspx?id=620 UN: druginfo@usask.ca PW: Mylan
4. Phone communication with Farzana, Mylan Medical Information, 1-844-596-9526, 17 Jul 2017

Jul. 17, 2017I have a patient on citalopram and I was going to give azithromycin but I got a drug interaction. What is the significance? details
 

Patient Age: 82
Patient Sex: F
Medical Problems: COPD - AECB
eGFR not available
Medication History: citalopram 20 mg PO OD
pantoprazole
Response: The interaction that would have been flagged is QT prolongation. Citalopram, especially at higher doses can prolong QT; 20 mg daily is considered the maximum dose in elderly patients.(1) Given the patient's age, gender, and use of citalopram, addition of azithromycin puts her at moderate risk of QT prolongation(2), which is not dire but other agents are available that do not prolong QT and are better agents for acute exacerbations of chronic bronchitis: amoxicillin, doxycycline, SMP/TMX (3,4)
References: 1. RxTx - eCPS Celexa
2. QT prolonging drugs: assessement and management of risk in Jade/DzFiles/3. Cardiovascular/QT
3. Anti-infective guidelines for community-acquired infections
4. Bugs and Drugs app

Jul. 18, 2017I know Wellbutrin XL is contraindicated for patients with bulimia. In patients with bulimia, are there any special considerations when starting Vyvanse? Vyvanse has been shown to be helpful for binge-eating disorder, but I'm wondering if it might also help with a patient who has bulimia. I'm not sure if there is anything I should watch out for because she is purging multiple times a day. details
 

Response: The bottom line is there are no data to determine if stimulants increase the risk of seizure in patients with bulimia nervosa (BN) nor to be able to predict who may be at higher risk if they do.
As you suggested, bupropion is contraindicated in patients with bulimia. I believe this is based on the DB-RCT in which the prevalance of seizures among the bupropion-treated patients was 5.8%, considerably higher than what had been found in the other trials using doses up to 450 mg daily.(23) The authors of this study - that was terminated early on account of the seizures - could not identify any common factors among the patients who experienced seizures and so suggested it is possible bulimia nervosa makes a patient more vulnerable to bupropion-induced seaizures. This implies patients with BN would have abnormal EEG readings; while this has been found to some degree, results have been inconsistent and based on small, methodologically-weak studies.(24)
I tried to find evidence of seizure triggers that would be more likely in patients with BN. I was thinking along the lines of electrolyte abnormalities but found in general the most common triggers of seizures are sleep-deprivation/fatigue, stress, flashing lights, and fever.(17-19) Electrolyte abnormalites or anything diet-related were not mentioned at all in any of these papers.
I next attempted to determine the relative risk of seizure of lisdexamfetamine compared to bupropion. I knew there would not be strong data as that would require an RCT involving both these drugs (or even bupropion and other stimulants) with seizure as the primary outcome; a study I knew would not exist. Nonetheless, I thought some observational data may be available. Unfortunately I did not find any comparison data. While stimulants seem to lower the seizure threshold (6) and increase the risk of seizure (9), I found several papers supporting the cautious use if stimulants in patients with comorbid ADHD and controlled seizure disorder. (11-13)
Finally, while limited, there have been six case reports of positive outcomes on bingeing/purgeing in patients with BN who were treated with a stimulant for comorbid ADHD.(21,22) There were no reports of seizures among these patients. However, clearly more than six case reports are required to determine if patients with BN may also be more vulnerable to seizures from stimulant therapy.
I found nothing in my research to predict which patients, if any, would be at higher risk of experiencing stimulant-induced seizure.
References: 1. Psychopharmacologic treatment of eating disorders: emerging findings. McElroy SL, Guerdjikova AI, Mori N, Keck PE Jr. Curr Psychiatry Rep. 2015 May;17(5):35. doi: 10.1007/s11920-015-0573-1. Review. PMID: 25796197
2. Practitioner review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, Dittmann RW, Graham J, Taylor E, Sergeant J; European ADHD Guidelines Group. J Child Psychol Psychiatry. 2013 Mar;54(3):227- 46. doi: 10.1111/jcpp.12036. Epub 2013 Jan 7. Review. PMID: 23294014
3. Comparison of lisdexamfetamine and dextroamphetamine exposures reported to U.S. poison centers Kaland, M.E., Klein-Schwartz, W. 2015 Clinical Toxicology
53(5), pp. 477-485
4. Clinical Handbook of psychotropic drugs, pg 260-264
5. RxTx CTC Eating Disorders
6. RxTx - eCPS
7. Managing the risks of ADHD treatments. Schneider BN, Enenbach M. Curr Psychiatry Rep. 2014 Oct;16(10):479. doi: 10.1007/s11920-014-0479-3. Review. PMID: 25135779
8. Recurrent aborted sudden cardiac death with seizures and rhabdomyolysis due to bulimia-induced hypokalemia: report of one case. Finsterer J, Stöllberger C. Rev Med Chil. 2014 Jun;142(6):799-802. doi: 10.4067/S0034-98872014000600016. PMID: 2532732
9. A cohort study of the risk of seizures in a pediatric population treated with atomoxetine or stimulant medications. McAfee AT, Landon J, Jones M, Bangs ME, Acharya N, Hornbuckle K, Wong J. Pharmacoepidemiol Drug Saf. 2013 Apr;22(4):386-93. doi: 10.1002/pds.3390. Epub 2012 Dec 26. PMID: 23280590
10. Risk factors for complications of drug-induced seizures. Thundiyil JG, Rowley F, Papa L, Olson KR, Kearney TE. J Med Toxicol. 2011 Mar;7(1):16-23. doi: 10.1007/s13181-010-0096-4.
PMID: 20661684
11. Attention deficit/hyperactivity disorder and interictal epileptiform discharges: it is safe to use methylphenidate? Socanski D, Aurlien D, Herigstad A, Thomsen PH, Larsen TK. Seizure. 2015 Feb;25:80-3. doi: 10.1016/j.seizure.2015.01.002. Epub 2015 Jan 8. PMID: 25645642
12. Treating children with attention-deficit/hyperactivity disorder and comorbid epilepsy. Kattimani S, Mahadevan S. Ann Indian Acad Neurol. 2011 Jan;14(1):9-11. doi: 10.4103/0972-2327.78042. PMID: 21633607
13. The use of psychotropic drugs in epilepsy: what every neurologist should know. Kanner AM. Semin Neurol. 2008 Jul;28(3):379-88. doi: 10.1055/s-2008-1079342. Epub 2008 Jul 24. Review. PMID: 18777484
14. The effect of pharmacotherapy for attention deficit hyperactivity disorder on risk of seizures in pediatric patients as assessed in an insurance claims database. McAfee AT, Holdridge KC, Johannes CB, Hornbuckle K, Walker AM. Curr Drug Saf. 2008 May;3(2):123-31. PMID: 18690990
15. Stimulant therapy and seizure risk in children with ADHD. Hemmer SA, Pasternak JF, Zecker SG, Trommer BL. Pediatr Neurol. 2001 Feb;24(2):99-102. PMID: 11275457
16. http://www.epilepsy.com/learn/triggers-seizures/nutritional-deficiencies
17. The impact of sleep loss on the facilitation of seizures: A prospective case-crossover study. Samsonsen C, Sand T, Bråthen G, Helde G, Brodtkorb E. Epilepsy Res. 2016 Nov;127:260-266. doi: 10.1016/j.eplepsyres.2016.09.014. Epub 2016 Sep 16. PMID: 27665308
18. Seizure-Precipitating Factors in Relation to medical Recommendations: Especially Those Limiting Physical Activity. Stanuszek A, Wnękowicz E, Kuźniar E, Krakowska K, Gergont A, Kaciński M. J Child Neurol. 2015 Oct;30(12):1569-73. doi: 10.1177/0883073815574334. Epub 2015 Mar 25. PMID: 25808459
19. Seizure precipitants (triggering factors) in patients with epilepsy. Ferlisi M, Shorvon S. Epilepsy Behav. 2014 Apr;33:101-5. doi: 10.1016/j.yebeh.2014.02.019. Epub 2014 Mar 15. PMID: 24632482
20. Psychotropic medications in adult and adolescent eating disorders: clinical practice versus evidence-based recommendations. Garner DM, Anderson ML, Keiper CD, Whynott R, Parker L. Eat Weight Disord. 2016 Sep;21(3):395-402. doi: 10.1007/s40519-016-0253-0. Epub 2016 Feb 1. PMID: 26830430
21. Reduction of bulimia nervosa symptoms after psychostimulant initiation in patients with comorbid ADHD: five case reports. Keshen A, Ivanova I. Eat Disord. 2013;21(4):360-9. doi: 10.1080/10640266.2013.797828. PMID: 23767675
22. Innov Clin Neurosci. 2013 Feb;10(2):30-3. Adjunctive Methylphenidate in the Treatment of Bulimia Nervosa Co-occurring with Bipolar Disorder and Substance Dependence.
Guerdjikova AI, McElroy SL. PMID 23556140
23. Horne RL, Ferguson JM, Pope HG Jr, et al. Treatment of bulimia with bupropion: a multicenter controlled trial. J Clin Psychiatry. 1988;49(7):262.
24. Pope H, McElroy S, Keck P, et al. Electrophysiologic abnormalities in bulimia and their implications for pharmacotherapy: A reassessment. Int J Eating Disorders. 1989; 8(2): 191
*PubMed "lisdexamfetamine bulimia"

Jul. 18, 2017A child on a ketogenic diet has been receiving Wampole calcium (NPN 80006877) as it is ketogenic-friendly. However, it is not concentrated enough and the mother is not able to administer the required dose of 20 ml. We were going to compound a more concentrated product and the drug plan suggested two other products (JAMP calcium citrate liquid, NPN 80068122 and SoluCal, NPN 80002626). Are these suitable substitutes? details
 

Response: The product the child is currently receiving is 20 mg/ml elemental calcium.(1) This is the same concentration as the SoluCal(1), so it will not be a suitable alternative. The JAMP product contains 33.3 mg/ml elemental calcium as calcium citrate(3); it's excipients include sucralose and xylitol as sweetening agents.(3)
References: 1. LNHPD
2. NIHB 2017 Drug Benefit list
3. Phone/email communcation with JAMP medical information

Jul. 18, 2017 Is there any evidence of Qvar (Beclomethasone) for eosinophilic esophagitis? A child has been prescribed Flovent (fluticasone) but the family cannot afford it. details
 

Patient Age: 6
Patient Sex: M
Medical Problems: eosinophilic esophagitis
Medication History: Flovent 250 mcg BID
PPI
PO budesonide
Response: Definitely the majority of research for topical corticosteroid using inhaled corticosteroids for the treatment of eosinophilic esophagitis (EE) has been conducted using fluticasone propionate.(1-5) In terms of beclomethasone dipropionate, I found only one case that was reported among the first four cases of EE treated with topical corticosteroids.(5) All that was reported was the dose (42 mcg/puff, 4 puffs BID) and that a rapid clinical response was observed within one week.(5)
The most common reason provided for preferring fluticasone propionate is its low oral bioavailability,(4,5) which has been found to be <1% (6) compared to ~26% with beclomethasone propionate. (7) While theoretically the Qvar should be just as effective as the Flovent®, the concern would be long term adverse effects of systemically absorbed corticosteroid.

I’m not sure if there are other factors at play here, but when I price out the inhalers, they all seem to be about the same price for approximate equivalent corticosteroid dosing, with the exception of mometasone:
Acquisition cost per 30 days(8,9): Qvar $80; Alvesco $83; Flovent $90 Asmanex $40
I also included Alvesco®, which also has low oral systemic absorption (<1%(6)) and for which one study of use in EE has been published.(11) As you can see the price is within range of the Qvar® and Flovent®. I also considered Asmanex® as it would be less expensive than the other agents when comparing pediatric high dose corticosteroid doses for asthma (8); however, the only study of mometasone in EE used aerosolized drug in adult patients (12) whereas Asmanex is a dry powder inhaler. It would seem very difficult to access the powder out of a dry powder device (requiring a quick breath) without inhaling most of the dose instead of swallowing; no studies were found using this type of device in EE.

If the cost of the Flovent® is not manageable for the family, I doubt a $10/month saving will be much of a reprieve. If not done already, the family can apply to the Saskatchewan Drug Plan and Extended Benefits Branch for special coverage to help offset costs.
References:
1. Noel RJ, Putnam PE, Collins MH, et al. Clinical and immunopathologic effects of swallowed fluticasone for eosinophilic esophagitis. Clin Gastroenterol Hepatol. 2004;2:568–75.
2. Konikoff MR, Noel RJ, Blanchard C, et al. A randomized, double-blind, placebo-controlled trial of fluticasone propionate for pediatric eosinophilic esophagitis. Gastroenterology. 2006;131:1381–91.
3. Butz BK, Wen T, Gleich GJ, et al. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology 2014;147:324–333.
4. Andreae DA, Hanna MG, Magid MS, et al. Swallowed fluticasone propionate is an effective long-term maintenance therapy for children with eosinophilic esophagitis. Am J Gastroenterol 2016;111:1187–1197.
5. Faubion WA Jr, Perrault J, Burgart LJ, et al. Treatment of eosinophilic esophagitis with inhaled corticosteroids. J Pediatr Gastroenterol Nutr. 1998 Jul;27(1):90-3.
6. Hübner M, Hochhaus G, Derendorf H. Comparative pharmacology, bioavailability, pharmacokinetics, and pharmacodynamics of inhaled glucocorticosteroids. Immunol Allergy Clin North Am. 2005 Aug;25(3):469-88.
7. Daley-Yates PT, Price AC, Sisson JR, et al. Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following IV, PO, intranasal and inhaled administration in man. Br J Clin Pharmacol. 2001 May;51(5):400-9.
8. Rutherford L, Crawley A, Jensen B, et al. Asthma: overview. RxFiles drug comparison charts. Saskatoon, SK: Saskatoon Health Region. [updated 01 Mar 2017; accessed 19 Jul 2017]. Available from: www.RxFiles.ca
9. RxTx [Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. CPS online: respective monographs. Available from: https://www.e-therapeutics.ca/
10. McKesson Canada; c2017 [cited 19 Jul 2017] PharmaClik; Available from http://clients.mckesson.ca Account required.
11. Schroeder S, Fleischer DM, Masterson JC, et al. Successful treatment of eosinophilic esophagitis with ciclesonide. J Allergy Clin Immunol. 2012 May;129(5):1419-21.
12. Bergquist H, Larsson H, Johansson L, et al. Dysphagia and quality of life may improve with mometasone treatment in patients with eosinophilic esophagitis: a pilot study. Otolaryngol Head Neck Surg. 2011 Oct;145(4):551-6.

Jul. 18, 2017Patient has eGFR of 22 ml/min and is on ASA 81 mg. When do you stop ASA in Chronic Kidney Disease? details
 

Patient Age: 77
Patient Sex: M
Medical Problems: CABG -couple of years ago.
Response: ASA has shown to quite markedly reduce the risk of major CV disease, MI, stroke, CV mortality and total mortality in patients with eGFR <45 ml/min.(2) Because patients with chronic kidney disease are at increased risk of CV events, use of ASA is recommended in this population by the National Kidney Foundation unless bleeding risks outweigh benefits(3) and by the American Heart Association.(4)
References: 1. http://thrombosiscanada.ca/?page_id=18# - Acetylsalicylic Acid (ASA)
2. http://kdigo.org/wp-content/uploads/2017/02/201203_Zanchetti.pdf
3. https://www.kidney.org/sites/default/files/How_to_manage_CKD_patients.pdf
4. Washam JB, Herzog CA, Beitelshees AL, et al.; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, Council on Functional Genomics and Translational Biology, Council on the Kidney in Cardiovascular Disease, and Council on Quality of Care and Outcomes Research. Pharmacotherapy in chronic kidney disease patients presenting with acute coronary syndrome: a scientific statement from the American Heart Association. Circulation. 2015 Mar 24;131(12):1123-49. doi: 10.1161/CIR.0000000000000183. Epub 2015 Feb 23. PMID 25712269
http://circ.ahajournals.org/content/circulationaha/early/2015/02/23/CIR.0000000000000183.full.pdf

Jul. 18, 2017Can SK pharmacists prescribe ulipristal? details
 

Response: Not currently; it is included in the Emergency Contraception guidelines, but these are in development only.(1)
References: 1. http://medsask.usask.ca/professional/guidelines-in-development/emergency-contraception.php

Jul. 19, 2017Can Vigamox eye drops be used in pregnancy? She is at about 10 weeks gestation. details
 

Response: Moxifloxacin has very limited absorption when administered ophthalmically - 0.02% that of oral administration.(1) Systemic absorption can be reduced by applying punctual occlusion following administration.(1) An alternative would be preferred if possible, but the American Academy of Ophthalmology suggests fluoroquinolone eye drops are safe in pregnancy.(2)
References: 1. Lexicomp
2. https://www.aao.org/focalpointssnippetdetail.aspx?id=43773f38-f7a5-477c-ab00-debf7501aa0b

Jul. 20, 2017Question about a person taking dutasteride 2.5 mg for hair loss. Lexicomp says this is the off-label dose but I've seen studies using 0.15 mg and have seen 0.5 mg elsewhere. Is 2.5 mg appropriate? details
 

Patient Age: 54
Patient Sex: M
Medication History: finasteride 1 mg since May
Response: Doses up to 2.5 mg have been used in studies.(1,3) However, not much more benefit was gained with 2.5 mg compared to 0.5 mg dosing (110 hairs per cm2 area compared to 95, respectively).(1) The 2.5 mg dose will definitely be much more expensive as the drug is only available as 0.5 mg capsules(2) and may be associated with more androgen-related adverse effects.
References: 1. Micromedex
2. PharmaClik
3. RxTx - CTMA Hair Care and Hair Growth

Jul. 20, 2017I have drug schedules of most vaccines. Can you help me find the scheduling for meningococcal (specifically Menactra)? details
 

Response: Meningococcus vaccine is schedule II.(1)
References: 1. NAPRA drug scheduling

Jul. 21, 2017What is the treatment of mild malaria? Patient was in chloroquine-resistant area. details
 

Response: Options(1,3):
Malarone: 4 adult tablets as one dose on three consecutive days.(2)
OR
doxycycline 100 mg BID x 7 days (5) in combination with quinine 500 mg (base) TID x 3-7 days (7 days if acquired in Southeast Asia)(4)
References: 1. CATMAT 2014
2. eCPS - Malarone
3. https://www.cdc.gov/malaria/diagnosis_treatment/clinicians2.html
4. eCPS - CPhA Quinine sulfate monograph
5. lexicomp

Jul. 21, 2017When treating MS exacerbation with prednisone 1250 mg every other day for 5 doses, is a taper required? details
 

Response: The need for a taper is not established and no guidelines exist to provide direction; some clinicians will taper and others will not but it is generally up to clinician experience and preference.(1)
References: 1. http://medsask.usask.ca/documents/newsletters/34.2%20MS%20Flares_Steroids.pdf

Jul. 25, 2017Is there a biphasic tramadol extended release that is 25%IR and 75%XR? details
 

Response: Tridural is a biphasic product (1,6) that releases 25% tramadol within the first two hours and 75% slowly over several hours.(4)
References: 1)Tridural product monograph
2)https://www.nps.org.au/radar/articles/once-daily-tramadol-extended-release-durotram-xr-for-pain
3) http://www.medsafe.govt.nz/profs/datasheet/d/durotramxrtab.pdf
4) Phone communication with Kayla, Paladin Labs, 1-888-867-7426 7 Aug 2015

Jul. 26, 2017Our patient was on Humira (adalimumab) and at the time of menopause it became less effective. She is equating this to the change in her hormones. She started HRT 6 years ago and is now on Simponi, that is working very well. However, she feels if she discontinues the HRT the Simponi will quit working. I told her I'm confident the loss of effectiveness of Humira was not related to menopause but am wondering if you can confirm this. Also, how can she taper her regimen of Estradot/Prometrium? details
 

Medical Problems: ankylosing spondylitis
menopausal x 6 years
Medication History: Humira - quit working so went to Simponi - working very well
Estradot 25 mcg patch twice weekly; Prometrium 100 mg PO OD
Response: There has only been one study to provide any sort of guidance on this question where exogenous estrogen was provided to premenopausal and menopausal women with ankylosing spondylitis (AS).(4) There were only five women in the menopausal group and all had active AS at the beginning of the study. Three were menopausal physiologically while menopause was induced iatrogenically. In total, seven women elected to take estrogen therapy, four of whom were in the menopausal group (conjugated estrogen 0.0625 mg on days 1-25 and clormadinone starting on day 16). After one month, peripheral arthritis subsided in these patients and did not recur while receiving therapy. The authors report relapse in four women who discontinued treatment; however, it is not reported to which group these women belonged nor if all patients were followed after discontinuation and only 4 of the 7 women who had taken estrogen therapy experienced relapse.
Estradot is a matrix patch (1) so can theoretically be cut in half and the patient to use 1/2 patch twice weekly. However, this is the lowest dose and it is reasonable to consider this the last step in the taper. Prometrium could be taken every other day if needed.
References: 1. RxTx - Estradot
2. RxTx - Simponi, Humira
3. Analysis of the effect of the oral contraceptive pill on clinical outcomes in women with ankylosing spondylitis. Mahendira D, Thavaneswaran A, Carty A, Haroon N, Anton A, Passalent L, Alnaqbi KA, Savage L, Aslanyan E, Inman RD. J Rheumatol. 2014 Jul;41(7):1344-8. doi: 10.3899/jrheum.130996. PMID: 24931958
4. Jimenez-Balderas FJ, Tapia-Serrano R, Madero-Cervera JI, et al. Ovarian function studies in active ankylosing spondylitis in women: clinical response to estrogen therapy. J Rheumatol 1990;17:497–502.
5. http://onlinelibrary.wiley.com/doi/10.1002/art.23321/pdf
6. http://www.eajm.org/sayilar/194/buyuk/42-6.pdf
*UTD

Jul. 26, 2017I dispensed a prescription for Incruse (umeclidinium bromide)but the patient has asthma not COPD. I thought there was a concern of bronchospasm with anticholinergics in asthmatics? Her MD said they're starting to use this agent more in asthmatics. Are there any concerns? details
 

Response: Long-acting anticholinergics (often specified with tiotropium) can be considered if exacerbations continue in adults with asthma despite appropriate inhaled corticosteroid and long-acting beta-agonist therapy.(1,3-5) Tiotropium (but not umeclidinium) has an indication for asthma in the US (but not Canada).(6) Umeclidinium may cause paradoxical bronchospasm, but so may salmeterol.(2)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Asthma.pdf
2. RxTx - eCPS
3. RxTx - CTC Ashtma in Adults
4. UTD - Treatment of severe asthma in adolescents and adults
5. http://ginasthma.org/2017-pocket-guide-for-asthma-management-and-prevention/
6. Lexicomp

Jul. 28, 2017We have a prescription for "low carb"Gylcopyrrolate. Do you have a formula for that? This patient has epilepsy and was prescribed a ketogenic diet. details
 

Response: There are two possibilities: provide injectable orally, undiluted; or compound a suspension using powder and OraSweet SF/OraPlus.(4) For a dose of 0.2 mg QID, per 30 days the injectable would cost $400 at a minimum whereas a suspension would be ~ $34.(3) The sweeteners in OraSweet SF are sorbitol and saccharin, so if these are acceptable for the child's ketogenic diet, this would be the best alternative.
References: 1. All book marked compounding references (sick kids, IJPC etc)
2. Victoria Hospital Compounding Manual
3. PharmaClik
4. IJPC Jul/Aug 15(4): 337
5. IJPC May/Jun 8(3): 218
6. https://www.perrigo.com/files/rx/pdfs/pds173-ORA-Plus.pdf
7. https://www.perrigo.com/files/rx/pdfs/pds175-ORA-Sweet%20SF.pdf

Jul. 28, 2017We have a question from a woman travelling to Australia for 6 weeks about how to transport her Humira. If she decides not to have it for 4 weeks, what sort of effects can she expect? Return or worsening of her symptoms? details
 

Patient Age: 59
Patient Sex: F
Medical Problems: ?
Crohn's
Medication History: Humira x 7 years - controlled for 6 years

stopped bc of shingles x 3 months without any problems
Response: The most likely scenario of missing doses is relapse of her condition; considering her experience of missing three months' treatment with no ill effect, it is unlikely she'll experience relapse if one or two doses are missed; however, she should try her best to travel with the product and keep it adequately stored.
As for travelling with the product, Humira can be stored at room temperature for up to 14 days, but once it reaches this temperature, it must be used within 14 days (2) such that the patient will not be able to allow the injection required at 4 weeks to reach room temperature. Certainly she should have an insulated bag with ice to keep her Humira cool.(3,4) Transport Humira in the prescription labelled box and take empty ziploc bags.(3,4) When on the plane, if possible and the patient feels comfortable, ask if the Humira can be stored in the plane's fridge. Regardless, ask the flight attendants for more ice (to be put in the empty ziploc bags) at the end of the flight or whenever the ice melts.(4) When arrival at destination, put the Humira in a fridge as soon as possible.(3,4) If no fridge is available, the insulated pack will need to restocked with fresh ice whenever necessary. It will make the patient's trip more enjoyable if she plans ahead: check with the airports regarding putting her travel pack through security; check with the airline in advance regarding potential storage in the fridge; check with the accomodations regarding refrigeration possibitilies. Ideally, she will leave soon after her last dose so that she only requires two doses while abroad. The product used for the dose at 2 weeks does not require refrigeration as it will be used within 14 days; however, the product used for the 2nd injection on her trip needs to be refrigerated anyway. Then she would receive her next dose very quickly once back home. It may be a good idea to take three doses in the event of unforseen circumstances that delay her return home.
References: 1. UpToDate : Overview of the medical management of severe or refractory Crohn disease in adults
2. RxTx - Humira
3. https://www.abbviecare.ca/humira/humira-ra/travelling-with-humira
4. https://rheumatoidarthritis.net/living/traveling-with-refrigerated-medications/

Jul. 31, 2017We have a patient who recently had an Supraventricular Tachycardia (SVT) attack. It has been over 3 years since she last had one. Many years ago, she was on propranolol to manage her hypertension, which also prevented SVT attacks. Because propranolol wasn't controlling her hypertension, her mediactions was changed; first changed to ramipril then to losartan, then losartan/hctz as she is on currently. After her SVT attack was controlled, she was discharged with an prescription for metoprolol 12.5mg once daily for 20 days, to be taken in an attack. I'm not finding much information regarding oral metoprolol use in a "pill in the pocket" method, so I'm wondering if you could help out regarding dose and duration of such a treatment. details
 

Patient Age: 63
Patient Sex: F
Medical Problems: -hypertension
-high cholesterol
-depression/anxiety
-infrequent bouts of Supraventricular Tachycardia
-overactive bladder
Medication History: -Losartan/HCTZ 100/12.5mg od
-Lovastatin 20mg od
-citalopram 20mg od
-Vesicare 5mg od
-Vagifem 10mcg every other day
Response: 1. Beta-blockers have very limited evidence for use as a pill-in-the-pocket for an SVT attack. The 2015 AHA guidelines for SVT management (1) give this recommendation:
" IIb C-LD 3. Self-administered (“pill-in-the-pocket”) acute doses of oral beta blockers, diltiazem, or verapamil may be reasonable for ongoing management in patients with infrequent, well-tolerated episodes of AVNRT" (Recommendation level: IIb C-L) "
2. The "recommendation level IIb C-L" means treatment may be considered, but additional studies are needed, as only poor quality studies exist on this topic. The studies where this recommendation comes from (2,3) were testing a diltiazem and propranolol combination single dose given at onset of SVT symptoms.
3. There are no specific studies looking at just monotherapy with metoprolol as a pill-in-pocket strategy, so advice about dosing will not be evidence based. In the propranolol studies, they used 160mg propranolol in combination with diltiazem 120mg. Propranolol 160mg is a medium/maintenance dose, whereas the prescribed metoprolol 12.5mg seems likely too low to be used this way. In those two studies with propranolol, syncope was a major drawback to this strategy.
References: 1. http://www.sciencedirect.com/science/article/pii/S0735109715058404?via%3Dihub#bib241
2. https://www.ncbi.nlm.nih.gov/pubmed/11216977
3. https://www.ncbi.nlm.nih.gov/pubmed/3964710
*Dynamed Plus, management of SVT
*UpToDate, management of SVT
*medline literature search

Aug. 1, 2017Are there any direct numbers for an increased risk of atrial fibrillation development and alcohol consumption? details
 

Response: There appears to be an association between heavy alcohol use and development of atrial fibrillation:
1. http://circ.ahajournals.org/content/112/12/1736.short
- >35 drinks per week = hazard ratio of 1.45
2. http://www.sciencedirect.com/science/article/pii/S0002914903017090
- Data from the Framingham studies
- Moderate consumption = no risk
- >36g/d = increased risk (Relative risk of 1.34)
3. http://www.sciencedirect.com/science/article/pii/S0735109710044955
- Highest level of alcohol intake (considered to be 2 or more drinks per day in this analysis) had a relative risk of 1.51 versus the lowest level of intake (and lowest levels of intake still had an increased risk over not drinking)
4. http://www.sciencedirect.com/science/article/pii/S0735109714025133
- >21 drinks per week had a relative risk of 1.39; another analysis shows a relative risk of 1.47 for 5 drinks/day.
References: 1. http://circ.ahajournals.org/content/112/12/1736.short
2. http://www.sciencedirect.com/science/article/pii/S0002914903017090
3. http://www.sciencedirect.com/science/article/pii/S0735109710044955
4. http://www.sciencedirect.com/science/article/pii/S0735109714025133

Aug. 2, 2017Do you have a formula for butt balm 1-2-3 protective paste? details
 

Medical Problems: diaper rash
child
Response: A formula for 1-2-3 Protective Paste has been developed in Saskatoon but it is intended for patients undergoing radiation.(1) There is no standard formula to treat diaper rash but the components are the same: astringent, antifungal, and protectant.(3-6) The two formulae that may be most appropriate for the caller:
aluminum acetate solution 5g
Aquaphor Ointment 20g
Nystatin Cream 30 g
ZnO 20% ointment 30g (3)
OR
Emanuel Butt Paste:
karaya gum 25g
nystatin cream 10g
desitin ointment 12.5g
eucerin qs to 100g (4)
References: 1. Phone communication with Vera, BSP, Saskatoon Cancer Centre 655-2680, 24Nov2015
2. PharmaClik
3. IJPC 2011 15(6): 464-69
4. IJPC 2009 13 (5): 339
5. http://www.dermtek.com/products/dermburo.html
6. From previous call: . Foldvari, M. Dermatological preparations: ointements and gels. Hosp Pharm Pract. 1993. In print files - extemporaneous compounding - topical
*PL

Aug. 2, 2017I'm wondering if its advisable to split tablets of combination drugs? I know that typically if a drug is not coated and has no modified release properties, its generally considered okay to split. But I've come across some references that advise against splitting combination medications. I'm wondering specifically about tramacet and ramipril/hctz currently. details
 

Response: Pharmacist’s Letter used to consider drugs with more than one active ingredient a reason not to split though this reason is no longer listed.(1) A few other references also did not mention multi-ingredient products as a precaution.(2-4) A product with >1 ingredient should not have any more chance of uneven distribution in the tablet than a product with only 1 active ingredient. As such, the same principles would apply: avoid splitting if precise dosing is required; ideally split only one tablet at a time having the patient take both halves before splitting the next tablet to help ‘even out’ dosing as well as to maintain tablet stability as long as possible.(1)
References: 1. Canadian Pharmacist's Letter 2014; 21(8):300830
2. http://medsask.usask.ca/documents/newsletters/30.6%20Guide_to_Medication_Crushing.pdf
3. http://www.humber.nhs.uk/Downloads/Services/Pharmacy/Guidelines/Breaking%20or%20crushing%20tablets.pdf
4. Jade\Dz files\24. General\ Administration - Enteral\Issues of Splitting 2011

Aug. 2, 2017Is there a list of banned drugs for sports competition? Teenager is going to nationals for soccer in October and was told there may be random drug testing so to avoid all OTC products. Is this necessary? details
 

Response: The World-Antidoping Agency (WADA) maintains a list of prohibited substances.(1) Stimulants, including decongestants, are on the list but not other OTC ingredients. However, it is possible the athletes were told to avoid all OTC products so as not to accidentally take a product containing a decongestant.
Canada Soccer complies with the Canadian Anti-Doping Program administered through the Canadian Centre for Ethics in Sport,(2) which does follow WADA.(3) The CCES website has a checker in which you enter the sport, country of purchase and then search for the drug. A search of "Benylin" brought up several results with DIN and a clear indication if the ingredients are banned at all.(4)
References: 1. https://www.wada-ama.org/en/prohibited-list
2. http://www.canadasoccer.com/the-canadian-anti-doping-program-p151943
3. http://cces.ca/canadian-anti-doping-program
4. www.globaldro.com.

Aug. 2, 2017I have a patient who had her first dose of DMPA and was due for the next dose on July 13th (12 weeks). In the last week she had intercourse for the first time and says a condom was used. I did urine screen and there is no elevation of HCG (even though it wouldn't be elevated this early anway). I'm not sure if I should give her the next dose or wait a month to confirm she isn't pregnant? details
 

Patient Age: 17
Patient Sex: F
Response: Tomorrow will be 15 weeks since her dose. Since this is more than 14 weeks ago and assuming worst case scenario that patient did not use protection, emergency contraception can be offered if the intercourse was within the last 5 days and the next dose should be given as soon as possible. Urine beta-HCG should be repeated in three weeks to confirm no pregnancy.(2) Although the hormone is contraindicated in human pregnancy, inadvertent exposure to therapeutic doses does not appear to represent a significant risk of structural defects. Fetal growth restriction might be a low-risk complication if MPA is administered within 4 weeks of conception. (1)
References: 1. Briggs
2. SOGC - missed contraceptive

Aug. 4, 2017I have a 5 yo girl with lazy eye who is prescribed atropine eye drops twice weekly. All my references say to use daily. Would this be appropriate? details
 

Patient Age: 5
Patient Sex: F
Response: Atropine is administered to the sound eye to reduce focussing ability thereby providing an advantage to the amblyopic eye and encouraging its use. Weekend use is considered for those with mild to moderate severity.(2)
References: 1. UTD - Patient education: Crossed eyes and lazy eye (The Basics)
2. UTD - Amblyopia in children: Management and outcome

Aug. 4, 2017Patient is 87 years old and just started risedronate. She also has poor renal function. Even if her renal function were good, is there any benefit to her starting this at her age? details
 

Patient Age: 87
Patient Sex: F
Medical Problems: CrCl = 20 ml/min
dementia - forgets to take meds
Response: Risedronate is not the best choice given her renal function is such that risedronate (or any other bisphosphonates) is not recommended.(1) Furthermore, If she does remember to take her medications, she is unlikely to remember to take correctly - i.e. in the morning with full glass of water, remaining upright for 30 minutes and before any food - thereby putting her at greater risk of esphageal irritation/damage and/or lack of absorption (if she takes with food).
The only treatment for osteoporosis in which renal function is of relatively little consequence is denosumab (Prolia) (1) which is a subcutaneous dose every 6 months that may be more appropriate. However, she does not meet criteria for EDS of denosumab.(3) Whether to treat osteoporosis is somewhat of a judgment call based on life expectancy(time-to-benefit is 1-3 years [1]), risk factorsr, and patient values.
References: 1. GeriRxFiles
2. medstopper.com
3. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf

Aug. 4, 2017Are Dovonex cream and ointment still available or is only Dovobet available? details
 

Response: Dovonex cream has been discontinued from the market.(1) Dovonex ointment is available. (1,2)
References: 1. DPD
2. PharmaClik

Aug. 4, 2017I have an infant who reacted to azithromycin (body rash). I need to give some vaccines but there are trace amounts of neomycin and streptomycin in some. Do I need to withold the vaccination? details
 

Response: Azithromycin, a macrolide, is not related to neomycin and streptomycin, aminoglycosides.(1) There is no concern giving the vaccines.
References: 1. Lexicomp

Aug. 4, 2017A specialist told a patient to drink Fleet enema to increase phosphate levels. He has been drinking 15 ml daily. However, patient was at his GP who said he can't drink the enema. Is it a problem? details
 

Response: There are two types of Fleet enemas: regular Fleet enema that is a source of phosphate and contains sodium phosphates as well as benzalkonium chloride and edetate disodium in purified water. (1) There is no problem with drinking this solution.
Fleet Enemal mineral oil is 100% mineral oil (1), which should not be taken orally as there is a risk of aspiration in elderly patients.
I did suggest there are oral solutions available that can be used as a substitute to phosphate tablets during the shortage.(2)
References: 1. eCPS
2. http://medsask.usask.ca/documents/drug-shortages/Sodium%20Phosphate.pdf

Aug. 4, 2017Are there any drug interactions beteen methotrexate (MTX) and ethosuximide (Zarontin) or divalproex? details
 

Medical Problems: history of seizure
Medication History: Zarontin, divalproex
Response: No interactions are listed by Lexicomp.(1) Stockley's cites two case reports of reduced valproic acid levels but both involved high-dose MTX, one in combination with other antineoplastics.(2) Drugs.com suggests to be cautious of additive hepatotoxicity. (3) There is no reason to avoid the combination so long as usual monitoring is maintained.
References: 1. Lexicomp
2. Stockley's
3. drugs.com

Aug. 5, 2017Is there an alcohol free chlorhexidine .12% in Canada. details
 

Response: Two chlorhexidine 0.12% products licensed in Canada do not contain alcohol: Euro-Pharm International Chlorhexidine Alcohol-free (DIN 02463032) and Gum Paroex (DIN 02384272).(1) Only Gum Paroex is available at McKesson.(3)
References: 1. PMs from DPD
2. AHS Compounding Manual
3. PharmaClik
4. IJPC 2000;Mar/Apr (4): 128

Aug. 5, 2017Do you have information on H.pylori resistance rates in Saskatoon? details
 

Response: Helicobacter infection is diagnosed using one or more of several different methods, including antibody detection (least specific approach), fecal antigen detection, and urea breath testing, and culture of gastric biopsies. Culture is not used widely because it requires a biopsy specimen and because culture is not always successful. We have cultured a handful of specimens and isolated H. pylori at the request of gastroenterologists who were treating refractory cases. Therefore I am unable to share any data on antimicrobial resistance rates.(1)
As you probably noticed, the recommendations in the Pharmacy Practice article (2) which isbased on the Toronto Consensus guidelines (3) assume resistance unless there is local susceptibility data to prove otherwise. The Toronto consensus group identified lack of availability of data on local susceptibility patterns and eradication success rates as a knowledge gap that has a major impact on the choice of therapy and hence best management. If you have any further
References: 1. Email from Levett, Paul HE0 at Sask Disease Control Lab
2. From triple to quadruple therapy - Pharmacy Practice - August 2017
3. The Toronto Consensus for the Treatment of Helicobacter pylori
Infection in Adults Gastroenterology 2016;151:51–69http://www.sciencedirect.com/science/article/pii/S0016508516301081?via%3Dihub

Aug. 8, 2017Is a live vaccine contraindicated in a client taking salbutamol, Zenhale, venlafaxine, clonazepam and nortriptyline? details
 

Response: While Zenhale contains the corticosteroid mometasone, inhaled corticosteroids are not considered immunosuppressive.(1)
Corticosteroid therapy is not a contraindication to immunization when steroid therapy is short-term (i.e., less than 14 days); or a low-to-moderate dose of prednisone or equivalent (less than 2 mg/kg/day, or less than 20 mg/day if weight > 10 kg); or long-term, alternate-day treatment with short-acting preparations; or maintenance physiologic replacement therapy; or administered topically, inhaled, or locally injected (e.g., joint injection). (1)
References: 1.https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html

Aug. 8, 2017Does a woman need Plan B if she is just finishing her period, but has had unprotected sexual intercourse (UPSI)? She is within 72 hours or UPSI. She is not on any other birth control. details
 

Patient Sex: F
Medical Problems: UPSI
Response: Yes, Plan B should be recommended under any of the following conditions: Unprotected intercourse is defined as no contraceptive method used, condom breakage, more than 2 OC-pills missed any time during the cycle, 1 pill missed in the first week, more than 7-day pill-free interval, more than 13-week interval between DMPA injections, ejaculation on external genitalia or sexual assault.(1)
References: 1.RxTx

Aug. 8, 2017A patient on dialysis 2-3 times per week has been prescribed Cipro for a UTI (250 mg BID x 9 days). Does the dose need to be adjusted? details
 

Medication History: www.renalpharmacyconsultants.com
Response: This daily dose is appropriate (2-5); most references (3-5) recommend dosing q24h but one reference does cite q12h dosing interval.(2)
References: 1. Jade\Dz Files\13. Genitourinary\2013 Dialysis of Drugs
2. Renal Drug Handbook
3. Lexicomp
4. Bugs and Drugs app - Adult dosing recommendations in renal impairment
5. RxTx - eCPS - CPhA Fluoroquinolones monograph

Aug. 8, 2017I am getting some questions regarding a Facebook post about someone who needs a dose of epinephrine on a monthly basis and that dual epinephrine injectors are available for $9.95. This woman is from the U.S. so not really applicable here, but are there any other cheaper alternatives available in Canada? I couldn’t find anything with McKesson. I just want to prepare myself. details
 

Response: Epipen is the only epinephrine available as autoinjector at McKesson.(1) Other auto-injectors have been approved (Taro-epinephrine, Emerade, Anapen [1]) and could possibly be available through other wholesalers. The case described on Facebook is that of a patient who requires a dose of epinephrine on approximately a monthly basis. In this situation, one may want to consider purchasing epinephrine ampoules and syringes as the ampoules are available as 10x1ml for $14.05 (2) Autoinjectors have been preferred over ampoule & syringe (4,5) due to low confidence of the general public in drawing up the drug (6) as well as inaccurate dosing and delays in administration via this method.(6) However, in a case like this, the patient and family members could become comfortable and proficient with the procedure as it is required on a regular basis. In the far more common case where injections are required infrequently, it is hard to become proficient.
References: 1. DPD
2. Pharmaclik
3. http://www.ismp.org/newsletters/nursing/issues/NurseAdviseERR201601.pdf
4. https://www.aaaai.org/ask-the-expert/epinephrine-in-anaphylaxis
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485331/#CR11
6. Simons FE, Chan ES, Gu X, Simons KJ. Epinephrine for the out-of-hospital (first-aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical? J Allergy Clin Immunol. 2001;108(6):1040–4.

Aug. 8, 2017Patient swallowed a Spiriva capsule. Do I need to send her to the doctor? details
 

Response: No. Tiotropium has low oral bioavailability(2,3); the patient should be instructed to take a dose via inhaler for today.(2)
References: 1. https://www.fda.gov/downloads/drugs/drugsafety/medicationerrors/ucm080689.pdf
2. https://www.ismp-canada.org/news/item/80/
3. https://www.boehringer-ingelheim.com/products/prescription_medicines/respiratory/copd/spiriva/public/images/Spiriva_COPD_HandiHaler_and_Respimat_August_2014.pdf

Aug. 8, 2017Is there a more concentrated formula for clozapine suspension? (Using 20 mg/ml formula and noticed transferred prescription was 62.5 mg/ml) details
 

Response: The only formulae and stability studies available are for clozapine 20 mg/ml. (1-5)
References: 1. ijpc.com
2. AHS Compounding manual
3. http://www.pharminfotech.co.nz/manual/Formulation/mixtures/clozapine.html
4. https://www.cjhp-online.ca/index.php/cjhp/article/view/331
5. Trissel's stability of compounded formulations on STAT!REF via SHIRP
*CHEO, SickKids

Aug. 10, 2017A patient was started on metformin because her doctor said there is some information to say it helps bilateral neuropathy, but I cannot find this information. details
 

Response: No evidence was found. Overwhelmingly, the search results address whether metformin causes neuropathy through vitamin B12 deficiency.(2-4)
References: 1. UTD - Treatment of diabetic neuropathy
2. A observational study in patients of diabetes using metformin causing vitamin B12 deficiency causing peripheral neuropathy. Das S, Chakraborty A. J Assoc Physicians India. 2016 Jan;64(1):91. No abstract available. PMID: 27728101
3. Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy. Ahmed MA, Muntingh G, Rheeder P. BMC Pharmacol Toxicol. 2016 Oct 7;17(1):44. PMID: 27716423
4. Metformin: Potential analgesic? Smith B, Ang D. Pain Med. 2015 Dec;16(12):2256-60. doi: 10.1111/pme.12816. Epub 2015 May 29. PMID: 26031427
*Cdn guidelines (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273712/pdf/prm-19-328.pdf),

Aug. 11, 2017We have a prescription for diltiazem 2% with lidocaine for anal fissures. What is the recommended % of lidocaine for this indication? details
 

Response: There are no studies comparing concentrations of lidocaine for use in anal fissure. All different concentrations have been used: 10%(1), 5% when combined with minoxidil(2), 3% (3), 2% (4) and 1.5% combined with nifedipine 0.3%.(5) Considering the last one is closest to the situation and is actually supported by some efficacy data(5), it would be reasonable to suggest to aim for about 1.5%.
References: 1. A prospective, randomized, double-blind study comparing the efficacy of diltiazem, glyceryl trinitrate, and lidocaine for the treatment of anal fissure in children. Cevik M, Boleken ME, Koruk I, Ocal S, Balcioglu ME, Aydinoglu A, Karadag CA. Pediatr Surg Int. 2012 Apr;28(4):411-6. doi: 10.1007/s00383-011-3048-4. Epub 2012 Jan 3. PMID: 22212494
2. Recent advances in the pharmacotherapy of chronic anal fissure: an update. Medhi B, Rao RS, Prakash A, Prakash O, Kaman L, Pandhi P. Asian J Surg. 2008 Jul;31(3):154-63. doi: 10.1016/S1015-9584(08)60078-0. Review. PMID: 18658016
3. https://www.drugs.com/pro/lidocaine-rectal-cream.html
4. http://colonrectalsurg.wustl.edu/en/Patient-Care/Colorectal-Disorders/Anorectal-Disorders/Anal-Fissure
5. Dis Colon Rectum. 2002 Nov;45(11):1468-75. Topical nifedipine with lidocaine ointment vs. active control for treatment of chronic anal fissure: results of a prospective, randomized, double-blind study. Perrotti P1, Bove A, Antropoli C

Aug. 11, 2017Our patient wants to get both Twinrix and Gardasil vaccinations. Can these be given on the same day? The Twinrix schedule is 0, 1, 6 and the Gardasil is 0, 2, 6 - will it be okay getting them 4 weeks apart? details
 

Response: Because neither of these vaccines is live, the timing, whether same day or 4 weeks apart, is not a concern; either is fine so long as the injections on the same day are at different locations.(2)
The usual schedule for Gardasil 9 in women 15 years and older is 0, 2, and 6 months; the minimum interval between the 1st and 2nd dose is 4 weeks, the minimum interval between the 2nd and 3rd doses is 12 weeks and the minimum interval between the 1st and 3rd doses is 24 weeks.(1)
The usual schedule for Twinrix in adults is 0, 1, and 6 months.(2) While minimum intervals are not available for the combined vaccine, the minimum intervals for hepatitis B - which has the same schedule - is 4 weeks between the 1st and 2nd doses, 8 weeks between the 2nd and 3rd doses and 16 weeks between the 1st and 3rd doses.(2)
As such both vaccines could be given at either 0, 1, 6 months or 0, 2, 6 months; because it is better the interval be extended than shortened(2), 0, 2, 6 months may be preferable.
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-9-human-papillomavirus-vaccine.html#a5_f
2. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-1-key-immunization-information/page-10-timing-vaccine-administration.html

Aug. 11, 2017I would like to check if our patient's medications interact with Ibgard. What is the active ingredient? details
 

Response: The only active ingredient in IBgard is peppermint oil 90 mg.(1,2)
References: 1. https://ibgard.com/faqs/
2. LNHPD

Aug. 11, 2017We have an inpatient with extensive Kaposi sarcoma getting palliative radiation. The resident is wondering if there is an alternative to topical alitretinoin to apply to a painful lesion on the penis as they want to avoid chemotherapy. details
 

Response: Imiquimod 5% cream applied three times per week under occlusion has some evidence for non-HIV kaposi sarcoma.(1)
References: 1. UTD - Classic Kaposi sarcoma: Clinical features, staging, diagnosis, and treatment

Aug. 11, 2017When switching from Humulin R to Humalog is it just a straight switch? details
 

Response: The conversion is unit per unit.(1)
References: 1. Canadian Pharmacist's Letter 2015; 31(11):311128

Aug. 11, 2017How do you adjust dosing of Septra (sulfamethoxazole/trimethoprim - SMX/TMP)for a patient on hemodialysis? I am finding different answers. details
 

Medical Problems: UTI
Response: Of three references checked, I also found three different answers (2,4,5) including not recommended in hemodialysis patients.(4) Suggested to go with trimethoprim 200 mg daily - if the C&S is sensitive to SMX/TMP, it is sensitive to trimethoprim (7) and no dose adjustment is required in dialysis.(2,4)
References: 1. Dialysis of Drugs
2. Renal Drug Handbook
3.Bugs and Drugs app
4. Lexicomp
5. Micromedex
6. CPhA monograph
7. Geri RxFiles

Aug. 11, 2017Our patient has blood pressure readings that range from 100/50 to 190/90 (diastolic always <100). Are there any medications that keep the peaks lower and the valleys higher? details
 

Patient Age: 89
Patient Sex: F
Medication History: ramipril 5 mg PO HS
Response: I would suspect either adherence or longevity of the drug (wearing off before next dose) are issues here. This patient is the caller's mother so he is confident she is adherent though admits she sometimes 'adjusts her doses according to her BPs'. The patient takes ramipril 5 mg at bedtime and experiences lows in the morning and highs in the evening. Suggested to split the dose to 2.5 mg twice a day. Otherwise, consider switching to chlorthalidone 12.5 mg orally once a day or a long-acting calcium channel blocker as these may be useful in isolated systolic hypertension,(1,2) should this continue to be an issue with the split ramipril dose.
References: 1. UTD - Treatment of hypertension in the elderly patient, particularly isolated systolic hypertension
2. CTC - Hypertension

Aug. 11, 2017This patient was started on Coversyl (perindopril) - experienced GI upset. He has known lactose intolerance. Do you know if there are any antihypertensives that don't contain lactose? details
 

Patient Age: 33
Patient Sex: M
Medical Problems: caller does not know age
Medication History: Coversyl - first agent tried
Response: Certainly not the only possibility but ramipril is a good starting point as three brands checked do not contain lactose.(2) The brand carried by the community pharmacy will need to be checked. Antihypertensives that are not appropriate because all brands contain lactose include indapamide, hydrochlorothiazide, and candesartan.(1,2)
References: 1. RxTx - eCPS
2. PMs from DPD

Aug. 17, 2017Our patient was on gliclazide MR 90 mg once daily. She went to the US and was started on glipizide 10 mg BID. Is this equivalent? details
 

Response: There are no direct dose comparisons since gliclazide is not available in the US and glipizide is not available in Canada. However, indirectly:
First of all, glipizide is available as a regular release and extended release. Generally the RR is given once daily but may be split into two doses. The ER is usually given once daily.(1,3) Therefore, it is assumed this patient is using regular release, but this will need to be confirmed.
A daily dose of 90 mg gliclazide MR ~ 10 mg glyburide daily. (4)
10 mg glyburide daily ~ 20 mg glipizide RR (divided in 2 doses) or 10 mg glipizide XL. These are within the usual the dosing ranges of 2.5-40 mg and 5-20 mg daily, respectively.(1)
As such, glipizide 10 mg BID is an appropriate starting point to substitue for gliclazide MR 90 mg daily. Certainly the dose may need to be adjusted.
References: 1. http://www.hosp.uky.edu/pharmacy/formulary/formtools/sulfonylurea.htm
2. RxFiles - http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-diabetes.pdf
3. Micromedex Drug Consult - Class Comparison: Antidiabetic Agents
4. Canadian Pharmacist's Letter 2009; 25(8):250842

Aug. 17, 2017Our patient had a copper IUD inserted about 24 hours ago. She started bleeding during the insertion and the MD was not concerned and considered the insertion successful. She is still spotting and wants to know if there is a time frame beyond which she should see MD? details
 

Response: Some degree of spotting or bleeding is common following insertion of an IUD.(3) In one study, the average duration was 4.5 days after insertion and the average pad requirement was 3.5 per day.(3) This traumatic bleeding may meld into the increased bleeding pattern associated with copper IUDs (3) (average 13 days bleeding in first month and 6 days in 12th month(1)), such that even if bleeding continues beyond 5 days, it is not necessarily worrisome.
The patient should seek medical attention if she experiences bleeding that is is heavy (soaking 1 pad per hour), severe or unrelenting pain/discomfort, and/or the inability to feel strings as these could be indications of uterine perforation or expulsion.(2,3)
References: 1. SOGC - Canadian Contraception Consensus (Part 3 of 4): Chapter 7 e Intrauterine Contraception
2. UTD - Intrauterine contraceptive device: Insertion and removal
3. UTD - Intrauterine contraception: Management of side effects and complications

Aug. 17, 2017We're seeing folic acid being prescribed once a week for methotrexate (MTX). Our last prescription was for 10 mg once a week yet we used to see prescriptions for 5 mg folic acid daily. Is 10 mg weekly sufficient? Also, I have always thought the folic acid should be given on a different day than the MTX. Is this true? details
 

Response: Dosing regimens and doses of folate supplementation for patients using low dose methotrextate (MTX) have not been established.(1-3) It has been shown that folate reduces the incidence of abnormal transminase elevation and discontinuation rates of MTX.(2) A trend was seen in reduction of GI side effects and stomatitis, which could possibly be captured in the discontinuation data.(2) Doses of folic acid <7 mg per week have not demonstrated any negative effect on MTX efficacy (3) though it is not known if higher doses may counteract the MTX.(2,3) While optimal dosing and frequency remains unclear, authors of one systematic review recommend (based on available studies) 1-5 mg per day, except on administration day or 5-10 mg per week, 24-48 h after MTX. (3)
References: 1. RxTx CTC - Rheumatoid Arthritis
2. Shea B, Swinden MV, Ghogomu ET et al. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. J Rheumatol 2014;41(6):1049-60. PMID 24737913
3. Acta Derm Venereol. 2016 Jan;96(1):23-8. doi: 10.2340/00015555-2081. Methotrexate Dosing Regimen for Plaque-type Psoriasis: A Systematic Review of the Use of Test-dose, Start-dose, Dosing Scheme, Dose Adjustments, Maximum Dose and Folic Acid Supplementation. Menting SP1, Dekker PM, Limpens J, et al.

Aug. 17, 2017Male patient with a urinary tract infection ( UTI) has been on Cipro x 2 weeks. I just received another prescription for a further 14 days. I find that for complicated UTIs 14 days minimum treatment, but I can't find how much longer you would treat. details
 

Medical Problems: complicated UTI; caller only briefly spoke to patinet who mentioned UTI/prostate (according to patient)
caller unaware if C&S undertaken
Medication History: Cipro started Aug 4 x 2 weeks (today is last day of tx)
Response: Cipro is considered a first line treatment for men with UTI. (1,2) However, there is considerable resistance to ciprofloxacin(2) so it would be nice to know if a C&S were undertaken prior to treatment. Men who are treated for UTI and have persisitent symptoms at the end of the 2 weeks should be reassessed for prostatitis.(2) Should this be the case, the extention of the prescription to 4 weeks is reasonable.(3) If there has been no improvement in symptoms, however, resistance should be considered and followed through with C&S and appropriate antibiotic treatment.
References: 1. Bugs and Drugs app - Complicated UTI
2. UTD - Acute uncomplicated cystitis and pyelonephritis in men
3. Bugs and Drugs app - Acute bacterial prostatitis

Aug. 21, 2017Our patient started on warfarin for deep vein thrombosis (DVT) and put on Lovenox (enoxaparin sodium - low molecular weight heparin fragment) to bridge. Does the Lovenox have any effect on INR? details
 

Response: While it is logical to assume low molecular weight heparins (LMWH) and unfractionated heparin would prolong the prothrombin time(PT) (and therefore, INR), most PT reagents contain heparin-binding chemicals that block this effect.(6) When plasma concentrations are high (such as after heparin bolus), these blockers may be overtaken.(6) However, patients may have an elevated INR when initiating warfarin possible due to protein C deficiency(2,6) or liver disease.(4,6) The LMWH needs to be given in conjunction with warfarin for at least 5 days.(2,3)
References: 1. eCPS - Lovenox
2. http://www.rxfiles.ca/rxfiles/uploads/documents/members/Warfarin%20Management.pdf
3. CTC - Venous Thromboembolism
4. UTD - Hemostatic abnormalities in patients with liver disease
5. UTD - Biology of warfarin and modulators of INR control
6. UTD - Clinical use of coagulation tests
* UTD - Heparin and LMW heparin: Dosing and adverse effects

Aug. 21, 2017Can Twynsta 40/5 mg be cut? details
 

Response: Twynsta contains telmisartan 40 mg and amlodipine 5 mg; they are immediate release(1) and are not on the Do Not Crush list.(2) There is no reason they cannot be split, though ideally they should be split one at a time and both halves taken before splitting the next tablet.(3)
References: 1. eCPS - Twynsta, Norvasc
2. http://www.ismp.org/tools/donotcrush.pdf
3. Canadian Pharmacist's Letter 2014; 21(8):300830

Aug. 21, 2017What are the current treatment protocols for subfoveal choroidal neovascular membrane (CNV)? Are there any comparative studies between treatments? What are the outcomes for the available treatments and what supportive evidence is available for the current treatment options? details
 

Patient Age: 39
Patient Sex: M
Medical Problems: Subfoveal choroidal neovascularization (CNV) from pathological myopia
178 lbs
Response: I found no guidelines for the treatment of pathological myopic choroidal neovascularization (mCNV). However, expert opinion considers anti-VEGF (Vascular Endothelial Growth Factor) therapy the treatment of choice,(1) which is supported by conclusions of a recent Cochrane Review (CR).(2) The anti-anti-VEGF agents available include ranibizumab (Lucentis®), bevacizumab (Avastin®) and aflibercept (Eylea®). Note: (pegaptanib (Macugen®) was discontinued in 2015.
Based on the current recommendation, for severe myopia, treatment with anti-VEGF agents is likely more beneficial than photodynamic therapy, laser, or no treatment (based on moderate- and low-certainty evidence). Currently there is nothing to suggest either ranibizumab or bevacizumab is superior to the other (based on moderate-certainty evidence: two head-to-head RCTs); for the treatment of mCNV, the only controlled trial involving aflibercept has compared it to sham treatment.(3)
Severe adverse effects have not been reported in the studies.(2) A review paper considers the following potential adverse effects of intravitreal anti-VEGF injection for mCNV: traumatic cataract, retinal detachment, endophthalmitis and sustained elevated intraocular pressure.(1)
As in the case of age-related macular degeneration, cost and off-label prescribing are issues with intravitreal use of anti-VEGF agents. In Canada, Lucentis® and Eylea® are indicated for mCNV. Avastin® is only approved for oncologic indications, is not approved for intravitreal administration and is available in vials containing 100 mg and 400 mg (dose for mCNV is 1.25 mg). There is a practice of repackaging Avastin® for substantial cost savings; a report by CADTH (4) regarding anti-VEGF agents for retinal conditions in general concluded all three agents in Canada are of equal efficacy and as long as Avastin® is packaged and handled properly, Avastin® should be the agent of choice based on a pharmacoeconomic standpoint.
References: References:
1. Adatia FA, Luong M, Munro M, et al. The other CNVM: a review of myopic choroidal neovascularization treatment in the age of anti-vascular endothelial growth factor agents. Surv Ophthalmol. 2015; 60(3):204-15.
2. Zhu Y, Zhang T, Xu G, Peng L. Anti-vascular endothelial growth factor for choroidal neovascularisation in people with pathological myopia. Cochrane Database of Systematic Reviews 2016, Issue 12. Art. No.: CD011160. DOI: 10.1002/14651858.CD011160.pub2.
3. Ikuno Y, Ohno-Matsui K, Wong TY, et al; MYRROR Investigators. Intravitreal Aflibercept Injection in Patients with Myopic Choroidal Neovascularization: The MYRROR Study. Ophthalmology. 2015 Jun;122(6):1220-7.
4. https://www.cadth.ca/sites/default/files/pdf/TR0009_anti-vegf-in-brief-e.pdf25902630 https://www.ncbi.nlm.nih.gov/pubmed/25902630

Aug. 21, 2017Can you check into safety of podophyllotoxin in children under 10 years old? details
 

Response: No data was found.
References: 1. RxTx - CTMA - Viral Skin Infections: Common and Flat Warts
2. UTD -Molluscum contagiosum
3. PubMed (Clinical queries)
4. van der Wouden JC, van der Sande R, Kruithof EJ, Sollie A, van Suijlekom-Smit LWA, Koning S. Interventions for cutaneous molluscum contagiosum. Cochrane Database of Systematic Reviews 2017, Issue 5. Art. No.: CD004767. DOI: 10.1002/14651858.CD004767.pub4.
5. David W. Kimberlin MD, FAAP, ed. 2015. Red Book®: 2015 Report of the Committee on Infectious Diseases - 30th Ed. Printed in the United States of America. American Academy of Pediatrics. ISBN-10: 1-58110-926-1, ISBN-13: 978-1-58110-926-9. ISSN: 1080-0131. STAT!Ref Online Electronic Medical Library. http://online.statref.com.ezproxy.shirp.ca/Document.aspx?docAddress=zQBxysDX9wErnVtemYV1sw%3d%3d. 8/21/2017 10:54:01 AM CDT (UTC -05:00).
6. SCOPUS: Int J Dermatol. 2006 Feb;45(2):93-9. Childhood molluscum contagiosum. Brown J, Janniger CK, Schwartz RA, et al.

Aug. 22, 2017A patient wants to know if there is a link with statins "influencing the male persona" (caller thinks he means sexual dysfunction or libido), or precipitating Alzheimers Disease? details
 

Response: 1. Initially there was some concern that statins might have an effect on cognition and short-term memory, but a recent meta-analysis in 2015 (1) found that statins did not harm cognition in either cognitively normal patients or those with Alzheimers disease (AD). In the few reports that raised concern about statins causing cognition issues, it was found that this occurred early on in therapy--within 30 days. Thus, it is reasonable to consider switching statins if cognition issues develop shortly after initiation. Pravastatin or rosuvastatin are thought to cause fewer cognition issues since they are more hydrophilic and do not cross the blood-brain-barrier as much as the other statins (2). Of note, statins are currently being studied for helping dementia.

2. For sexual dysfunction, another meta-analysis done in 2014 (3) actually showed statins aided erectile dysfunction through increasing blood flow. The authors note there has been theoretical concern that since testosterone is made from cholesterol, statins could lower testosterone in a person and decrease libido. One analysis (4) found that statins might lower testosterone by 0.66nmol/L. Whether this is a clinically significant decrease is undetermined, but if the patient believes this to be an issue, it would be reasonable to have his testosterone levels checked if low libido is his main concern.
References: 1. https://www.ncbi.nlm.nih.gov/pubmed?term=25575908
2. UpToDate, Statins: Actions, side effects, and administration
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023379/
4. http://academicworks.cuny.edu/cgi/viewcontent.cgi?article=1041&context=sph_pubs

Aug. 22, 2017We have a client who contracted paratyphoid. He was treated in hospital with ceftriaxone IV x 3 days and sent home with azithromycin. MD wants three stool specimens collected after treatment to ensure infection is cleared. Patient started HP-Pac today x 7 days. Do we need to wait until he is done the HP PAC before collecting the specimens for C&S? The doctor said to go ahead and start collecting but to be sure the last one is 48-72 hrs after finishing HP PAC. Is this appropriate? details
 

Medical Problems: paratyphoid
Medication History: finished azithromycin on 15th
Public Health going to send out kits for collection today
started HP PAC today
Response: After treatment for paratyphoid fever, patients are to have three stool samples to ensure eradication of the organism; these samples are to be taken at least 48 hours apart from one another and at least 48 hours after stopping antibiotics to which the organism is sensitive.(3,5,7) HP-PAC contains amoxicillin.(8) While S.typhi is often resistant to amoxicillin there are strains that are sensitive.(2,5) If previous sensitivity testing did not confirm resistance to amoxicillin, the first sample should not be taken until 48 hours after completion of the HP PAC.
References: 1. https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/typhoid-paratyphoid-fever
2. David W. Kimberlin MD, FAAP, ed. 2015. Red Book®: 2015 Report of the Committee on Infectious Diseases - 30th Ed. Printed in the United States of America. American Academy of Pediatrics. ISBN-10: 1-58110-926-1, ISBN-13: 978-1-58110-926-9. ISSN: 1080-0131. STAT!Ref Online Electronic Medical Library. http://online.statref.com.ezproxy.shirp.ca/Document.aspx?docAddress=UH5bT6Z1lD2z5o9rvk1OZA%3d%3d. 8/22/2017 5:19:25 PM CDT (UTC -05:00).
3. http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Epid/CD%20Manual/Chapter%201%20-%20CDC/EntericCasesandtheirContacts_May2013.pdf
4. http://sdcl-testviewer.ehealthsask.ca/SCI/What%20is%20new%20at%20SDCL/SDCL%20antibiogram%202016_updated.pdf
5. UTD - Treatment and prevention of typhoid fever Table: Antibiotic options and doses for treatment of typhoid fever
6. http://www.who.int/rpc/TFGuideWHO.pdf
7. http://apps.who.int/medicinedocs/documents/s20994en/s20994en.pdf
8. eCPS

Aug. 23, 2017For a person with paroxysmal atrial fibrillation (AF) who is on a low dose of beta blocker, is there evidence that increasing the dose of the beta blocker will improve symptoms? This patient is not a candidate for pill-in-the-pocket as her episodes are self-limited to ~ 30 minutes. details
 

Patient Age: 85
Patient Sex: F
Medical Problems: pAF
no other cardiac history
symptomatic episodes ~ 3x/month
BP avg 122/81 resting HR 59
Medication History: metoprolol 12.5 mg BID somewhat recently (within last year)
Response: This response is regarding any evidence of benefit to increasing the metoprolol dose for this 85 year old female patient with paroxysmal atrial fibrillation (pAF) who is still experiencing symptomatic AF episodes about three times per month despite metoprolol 12.5 mg BID.
This type of patient is not well-represented in trials, possibly because pAF patients are often treated with anti-arrhythmic therapy (daily or pill-in-the-pocket) or catheter ablation.(1,2) There has been a trial in which rate control therapy (β-blockers, calcium channel blockers, or digoxin) was titrated to two different heart rates (HR).(3) Titration was according to resting HR with the two targets being < 80 bpm (strict) and < 110 bpm (lenient). Even the strict is well above your patient’s current resting HR of 59 bpm. It needs to be noted the included patients had permanent AF, were younger than your patient (~68 yr) and outcomes were cardiovascular morbidity and mortality, not symptoms. End doses were not reported, however, significantly more patients in the strict group took digoxin (59.4% vs. 36.0%, p=0.006) and required more than one agent (data not directly available but use of any rate control agent in the lenient group was 313/261 patients compared to 450/256 patients in the strict group). This seems to indicate digoxin and/or more than one drug were required to achieve the HR target(s).
I found one trial that certainly asked a similar question to yours. In this trial, patients with pAF were randomly assigned to one of four groups and followed over a year.(4) The primary outcome was the incidence of symptomatic AF episodes. The four groups were: β-blocker + enalapril + spironolactone (Group A); β-blocker + spironolactone (Group B); β-blocker + enalapril (Group C); β-blocker alone (Group D). The β-blocker dose was titrated to achieve a resting HR of 60-70 bpm (more similar to your patient’s), spironolactone dose was 25 mg daily and the mean enalapril dose was 12.5 mg daily. At the end of 12 months, both spironolactone groups had significantly fewer episodes than the other two groups, there was no difference between the two spironolactone groups and the β-blocker-only group did not improve over baseline. The cumulative episodes at 1 year follow up were: 3.0 ± 0.8 per patient for group A, 3.4 ± 1.0 for group B, 5.9 ± 1.2 for group C and 10.4 ± 2.2 for group D. Some considerations with this study are that it was small (N=164), the patients enrolled experienced fewer baseline AF episodes than your patient (baseline ranged from 3 to 4 over 3 months) and were younger (mean age 66 yr).
Potential options:
1. Increasing metoprolol dose – whether an increased dose would improve palpitations has not been studied. It is a logical assumption and may be worth trying. However, her resting HR is already quite low and this may be the limiting factor.
2. Adding spironolactone 25 mg daily – as per results of SPIR-A(4) Certainly this strategy contributes to polypharmacy and may introduce new adverse effects but shouldn’t affect resting HR.
3. Switching to an anti-arrhythmic – I understand the hesitation with this suggestion. If it becomes a consideration, I suggest dronedarone or sotalol, simply because they do not require concomitant AV-nodal blocking as do flecainide and propafenone.(1,2)
References: References:
1. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. Birnie D, Nery P. Supraventricular tachycardia; [updated 01 May 2017; cited 25 Aug 2017].Available from: https://www.e-therapeutics.ca/
2. Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg. 2016 Nov;50(5):e1-e88.
3. Smit MD, Crijins JGM, Tijssen JGP, et al. Effect of lenient versus strict rate control on cardiac remodeling in patients with atrial fibrillation data of the RACE II (Rate Control Efficacy in permanent atrial fibrillation II) study. J Am Coll Cardiol 2011; 58(9):942-9.
4. Dabrowski R, Borowiec A, Smolis-Bak e, et al. Effect of combined spironolactone-β-blocker ± enalapril treatment on occurrence of symptomatic atrial fibrillation episodes in patients with a history of paroxysmal atrial fibrillation (SPIR-AF study). Am J Cardiol 2010;106(11): 1609-1614.

Aug. 26, 2017I am giving a Zostavax injection (subcutaneous). What size needle should I use? details
 

Medical Problems: Author AA. Title of web page [Internet]. Place of Publication: Sponsor of Website/Publisher; Year published [cited YYYY Mon DD]. Number of pages. Available from: URL DOI: (if available)

Editor AA, Editor BB, editors. Title of book. # edition[if not first]. Place of Publication: Publisher; Year. Pagination.
Medication History: Shreeve DF. Reactive attachment disorder: a case-based approach [Internet]. New York: Springer; 2012 [cited 2012 Nov 2]. 85 p. Available from: http://ezproxy.lib.monash.edu.au/​login?url=http://dx.doi.org/10.1007/978-1-4614-1647-0

O'Campo P, Dunn JR, editors. Rethinking social epidemiology: towards a science of change. Dordrecht: Springer; 2012. 348 p.
Response: A nursing texbook says 25 to 27G 5/8-1/2" needle is appropriate for subcutaneous injections.(1) Two references specific to subcutaneous vaccines recommend 23-25G 5/8" needle (2,3) and another specifies 25G 5/8".(4) According to this information, the best choice would be 25G 5/8"
References: 1. SHIRP\Nursing\eBooks\Lippincott's Nursing Procedures > Table of Contents > S > Subcutaneous Injection
2. http://www.immunize.org/catg.d/p2020a.pdf
3. http://www.pharmacist.com/ask-experts-proper-anatomical-location-administering-herpes-zoster-vaccine
4. https://docs.hamiltonfht.ca/dsweb/Get/Document-12374

Aug. 28, 2017The patient has been experiencing headaches since her teens. During pregnancies and after giving birth, the headaches continued to coincide with her cycle like clock work. My understanding is that she has approached her neurologist about hormonal therapy, as the headaches seem related to hormone fluctuation. He has deferred to her GP, saying he would not know about this connection. I do not know details, but I believe the patient cannot take estrogens for some reason. But if you could provide me with some information about the potential benefits of hormone therapy (E + P), the patient would have more information to ask her GP about. She is also curious as to whether hormone therapies would even be of potential benefit. Thank you! details
 

Patient Age: 37
Patient Sex: F
Medical Problems: Migraine headaches that occur during patient's menstrual cycle. Previously, patient would get migraines throughout the month. Now, with the cocktail of medications below, they are occurring less frequently throughout the month, but still occur during her cycle.
150kg
NKDA
Medication History: Amitriptyline 75mg hs
Naproxen 500mg BID starting 1 days before menses and continuing for 5 days
Rizatriptan ODT 10mg to be taken at headache onset. May repeat in two hours, maximum 3 per week.
Response: 1. Stabilizing hormone levels through hormone therapy is highly effective for reducing migraines (81% in one study (1) and those with mixed menstrual migraines and chronic migraine type also benefited significantly). It is thought that the drop and fluctuation in estrogen specifically around menstruation is responsible for triggering menstrual migraines. (2)

2. The main safety issue deals with the possible elevation of stroke risk in those with migraines. Migraines WITH aura, combined with hormonal therapy, would have a greatly elevated stroke risk and would generally be contraindicated. Migraine without aura poses no additional stroke risk when hormone therapy is used (2).

3. However, this patient is also >35 years old and 150kg. This, plus migraines (even without aura), would represent too much of a cardiovascular risk and DVT/PE risk for continuous hormone therapy. To limit this risk, one experimental estrogen replacement therapy has been tried in those with contraindications to continuous hormone therapy. A 0.1mg estradiol/24h patch is applied 1 day before the onset of bleeding and left in place for 7 days; this was somewhat effective in preventing the menstrual migraines, and since it limits exposure to estrogen, would be less of a CV or DVT risk (3,4). However, it is less studied and based on weak evidence, and one drawback is that many women still experienced migraines after withdrawing the estrogen treatment after 7 days.

4. Additionally, progesterone monotherapy appears to have no benefit (2):
" there is no evidence of any benefit of progestin-based therapies, including progestin-releasing intrauterine devices, on menstrual migraine or hormonally mediated headaches. Progestin contraceptives do not consistently inhibit the hormonal fluctuations that result in ovulation, and therefore do not lessen hormonally mediated headaches. This finding was demonstrated by a seminal work that isolated the effects of estrogen and progesterone on menstrual migraine and reported that declines in estrogen precipitated menstrual migraine, while declines in progesterone had no effect."
References: 1. https://www.ncbi.nlm.nih.gov/pubmed?term=18819179
2. UpToDate, Estrogen-associated migraine
3. https://www.ncbi.nlm.nih.gov/pubmed?term=18427072
4. https://www.ncbi.nlm.nih.gov/pubmed?term=17190936

Aug. 28, 2017Our patient is a 19 year old male with seasonal allergies and asthma. Nasal drip is a real problem for him. We have tried cetirizine, loratadine and desloratadine and he uses Flonase (fluticasone) nasal spray regularly. He finds that Aerius (desloratadine) works better than the other antihistamines. Is there any data about safety of using higher doses of Aerius on a regular, continuous basis? details
 

Patient Age: 19
Patient Sex: M
Response: 1. At high doses of desloratadine (assuming a max of 20mg / day used in some guidelines (1)), desloratadine may lose its non-sedating properties and begin to cause some drowsiness. However, the effect of long-term use is largely unstudied (2). One expert suggests (3) that although the longest studies are only up to 180 days long (and these were not using high doses), the long-term experience with antihistamines without apparent issues suggests a long duration of use would not pose any issues.

2. Toxicity symptoms with acute over-dosage of desloratadine 40-180mg include syncope, lethargy, drowsiness, nausea, vomiting and headache (4). Theoretically, chronic usage of a high dose of 20mg/d might start to show these symptoms.

3. One other theoretical concern is that second-generation antihistamines do still have some anticholinergic activity (5). Long-term, cumulative use of anticholinergics has been linked to development of dementia (6). This link typically occurs with much more potent anticholinergics like tri-cyclic antidepressants (TCAs) or diphenhydramine, and in older patients. However, high doses of desloratadine for years/decades might be enough to be a risk factor for dementia. If one wants to avoid this potential link altogether, cetirizine and fexofenadine are known to have zero cholinergic activity, even with high intravenous doses (5). Thus, these may be a safer option for high-dose, long-term use (Since he has tried cetirizine before, a higher dose, or fexofenadine, might be be worth trying).
References: 1. https://www.ncbi.nlm.nih.gov/pubmed/24034140?dopt=Abstract
2. https://www.researchgate.net/profile/Natalie_Schellack/publication/283758657_Long-term_antihistamine_therapy_revisited/links/56592a9208aefe619b2173a6/Long-term-antihistamine-therapy-revisited.pdf
3. http://www.aaaai.org/ask-the-expert/antihistamine-therapy
4. Micromedex DrugTox
5. https://www.ncbi.nlm.nih.gov/pubmed/15627436
6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358759/

Aug. 29, 2017In Lexicomp and other resources that I have found, the maximum dose of amoxicillin in pediatrics is 500 mg. However, I have received a prescription for 550 mg TID for a 5 year old. Is this evidence based? details
 

Response: If strep pneumoniae resistance needs to be overcome - such as in community-acquired pneumonia, some cases of otitis media and possibly sinusitis, a dose of 75-90 mg/kg/day is recommended divided in 2 or 3 doses.(1,2) The maximum dose is 3 g/day.(2,3) Practically speaking, if one were to adhere to a maximum of 500 mg per dose, only children up to 17 kg (37.5 lb) would be receiving this dose (based on TID dosing, even less if BID dosing).
References: 1. Bugs and Drugs app
2. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-ABX-Expanded.pdf
3. MUMS anti-infective guidelines app - acute otitis media in children

Aug. 31, 2017Why is estrogel a contraindication in otosclerosis? details
 

Response: 1. It is thought that since otosclerosis is more common in women, and seems to worsen or be first diagnosed during pregnancy (when estrogen is higher), that estrogen plays a strong role in developing otosclerosis. Thus, it is hypothesized that any treatment which could increase estrogen may worsen otosclerosis (1-4). This risk has not been proven to actually occur with estrogen therapy of any kind. The warning in the product insert isn't a complete contraindication, just a precaution.

2. Topical estrogen increases levels of estrogen less than oral therapy (5), so it will pose less of a risk, if the risk is even present. Suggest that the patient should be warned about the potential risk, to stop therapy if hearing worsens during therapy, and only use the estrogel if it will have an important benefit for her.
References: 1. http://american-hearing.org/disorders/otosclerosis/
2. https://www.ncbi.nlm.nih.gov/pubmed/19121641
3. https://www.researchgate.net/publication/7461189_Estrogen_and_hearing_A_summary_of_recent_investigations
4. http://pubmedcentralcanada.ca/pmcc/articles/PMC3075959/
5. Micromedex

Sep. 1, 2017Why are you not supposed to drink alcohol after Condyline application? details
 

Response: The monograph states in the contraindications: The consumption of alcoholic beverages for several hours after treatment is to be avoided.(1) It seems this information has been grandfathered from earlier information; no data can be found to support this statement.(2)
References: 1. eCPS - Condyline
2. Phone communication with Nicole, sanofi-aventis medical information, 1-800-265-7927, Sept 1, 2017

Sep. 6, 2017I am wondering about the interchangeability of Teva-progesterone (DIN 02439913) and Prometrium (DIN 02166704) for vaginal use. For oral use I have filled the generic and have no concerns of interchanging them; however, I am hesitant to fill the generic for vaginal use in the instance of risk for pre-term labour as I haven't found any documentation of the generic use and given that it is for maintaining the pregnancy, I am hesitant to fill the generic form unless I know it will work the same. I am wondering if when determining the interchangeability if it was based on oral use only, versus topical vaginal use, my concern/question would be whether the tablet component will break down the same way as the prometrium and provide same absorption? Would you fill the generic form when dispensing for this use? details
 

Response: There should be no concerns using Teva-progesterone capsules (DIN 02439913) in place of Prometrium capsules for vaginal use for the following two reasons:
Different dosage forms and routes of administration – oral, vaginal, and IM (hydroxyprogesterone, not available in Canada)forms of progesterone have been shown to be effective for reducing preterm birth in women with prior preterm birth.(11-13)
Both products are gelatin capsules (5,6), which dissolve easily. The non-medicinal ingredients of both are also similar:
​Non-medicinal ingredients of micronized progesterone capsules​
​Prometrium (6) ​Teva-micronized progesterone(5)
​oil (sunflower) ​ oil (fractionated coconut, peanut)
​ gelatin ​ gelatin
​ glycerin ​glycerin
​ soya lecithin lecithin
​ titanium dioxide ​titanium dioxide, red iron oxide
There would not have been any kinetic data of the vaginal route submitted by Teva since it’s an off-label route of administration and they have no obligation to provide such information.
References: 1. Rationale and design of SuPPoRT: a multi-centre randomised controlled trial to compare three treatments: cervical cerclage, cervical pessary and vaginal progesterone, for the prevention of preterm birth in women who develop a short cervix. Hezelgrave NL, Watson HA, Ridout A, Diab F, Seed PT, Chin-Smith E, Tribe RM, Shennan AH. BMC Pregnancy Childbirth. 2016 Nov 21;16(1):358. PMID: 27871275
2. Vaginal progesterone as maintenance treatment after an episode of preterm labour (PROMISE) study: a multicentre, double-blind, randomised, placebo-controlled trial.
Palacio M, Cobo T, Antolín E, Ramirez M, Cabrera F, Mozo de Rosales F, Bartha JL, Juan M, Martí A, Oros D, Rodríguez À, Scazzocchio E, Olivares JM, Varea S, Ríos J, Gratacós E; PROMISE Collaborative Group. BJOG. 2016 Nov;123(12):1990-1999. doi: 10.1111/1471-0528.13956. Epub 2016 Mar 30. PMID: 27028759
3. Vaginal progesterone prophylaxis for preterm birth. Papoutsis D, Antonakou A. Lancet. 2016 Sep 17;388(10050):1159. doi: 10.1016/S0140-6736(16)31612-9. Epub 2016 Sep 16. No abstract available. PMID: 27650092
4. sdlfksdj
5. PM on DPD - Utrogestan; Teva micronized progesterone
6. Prometrium PM eCPS
7. SOGC update http://old.sogc.org/wp-content/uploads/2013/01/guiJOGC202TU0801.pdf
8. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 900646, Prevention of preterm labor and preterm birth; [updated 2016 Sep 10, cited place cited date here]; [about 27 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=900646. Registration and login required.
9. PharmaClik
10. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 116364, Recurrent pregnancy loss; [updated 2015 Jun 19, cited place cited date here]; [about 18 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=116364. Registration and login required.
11. Likis FE, Edwards DR, Andrews JC, et al. Progestogens for preterm birth prevention: a systematic review and meta-analysis. Obstet Gynecol 2012; 120(4): 897-907
12. Dodd JM, Jones L, Flenady V, Cincotta R, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database of Systematic Reviews 2013, Issue 7. Art. No.: CD004947. DOI: 10.1002/14651858.CD004947.pub3.
13. Sotiriadis A, Papatheodorou S, Makrydimas G. Perinatal outcome in women treated with progesterone for the prevention of preterm birth: a meta-analysis. Ultrasound Obstet Gynecol. 2012 Sep;40(3):257-66.

Sep. 6, 2017According to STI guidelines treatment for gonorrhea is ceftriaxone 250 mg IM + azithomycin 1g PO. I have a patient treated with doxycycline but was also given ceftriaxone 2g IV one dose. Would this treat the gonorrhea or does she need the IM dose? details
 

Response: Concentrations following 2g IV are well above those for 0.5 g IM and at no point over 24 h is the concentration from the IM dose lower.(3) As such, this dose of IV ceftriaxone will be adequate treatment.
References: 1. Trick of the Trade: IV ceftriaxone for gonorrhea - Academic Life in Emergency Medicine - https://www.aliem.com/2012/10/trick-of-trade-iv-ceftriaxone-for/
2. DrugDex
3. Sandoz Ceftriaxone dose from FDA - https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/065168s019lbl.pdf

Sep. 6, 2017Our patient has lupus and continuous chest infections and wants to go on lecithin. Are there any problems with this? details
 

Patient Age: 87
Patient Sex: M
Medication History: metoprolol, tamsulosin, atorvastatin, Myrbetriq
prednisone 5 -10 mg daily, alendronate
Response: There are no known reasons for this patient to avoid lecithin unless he has egg or soy allergies.(1)
References: 1. Natural Medicines Comprehensive Database

Sep. 6, 2017Other than blood pressure risk and risk of water intoxication what do we know about using DDAVP longterm in children for bed wetting? details
 

Patient Age: 12
Patient Sex: M
Medical Problems: nocturnal enuresis
Medication History: DDAVP
Response: The data is sparse to inform this particular scenario; the main reason is that definition of long-term has typically been 6 months. A 2002 review does include long-term studies of desmopressin use in patients from children to adults.(1) The studies included use of both tablets and intranasal spray though the numbers receiving each dosage form are not reported. Of the 9 included trials, one was a double-blind, placebo-controlled crossover while the others were open and uncontrolled. Four studies followed patients beyond six months though only one of these studies(2) followed beyond 12 months.

Most studies included in the review did routinely investigate lab data, vital signs and adverse effects in which no clinically significant changes in blood pressure, blood chemistry, hematology, or urine analysis were reported; 7 patients did develop hyponatremia with no clinical symptoms. Of 1083 patients treated, 53 adverse events were reported, the most common being headache (2%) and it seems (though is not clear) that only one patient discontinued on account of an adverse effect, shich was fluid retention in a patient with a history of hypertension.

The study that appears to be of most interest that was included in the above review is titled, “Long-term use of desmopressin tablets in adolescents and adults with primary nocturnal enuresis (PNE)” and included follow-up of 21 months.(2) Unfortunately, I am not able to access this study; notice that the author of the review is the lead investigator of this study.

I can understand some hesitation to use this information based on the fact the review I included was published in 2002. All studies I found published since assessing long-term use of desmopressin were 6(3-5) or 12(6) months in duration. None of these reported any significant adverse effects.

One further point is that a study in children suggests tapering desmopressin may decrease relapse rates at 12 weeks.(7) Children in whom the dose was reduced by 50% for 2 weeks or who took the original dose every other day for two weeks relapsed less (39 and 42%, respectively) than those who were abruptly discontinued and given placebo for 2 weeks or who were abruptly discontinued with no placebo (53 and 55%, respectively). As such, the next discontinuation trial may want to include a taper.
References: 1. UTD - Nocturnal enuresis in children: Management
2. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - 2017. Record No. 116161, Enuresis; [updated 2017 Aug 10, cited 06 Sep 2017]; [about 18 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=116161. Registration and login required.
3. https://pathways.nice.org.uk/pathways/bedwetting-in-children-and-young-people#path=view%3A/pathways/bedwetting-in-children-and-young-people/desmopressin-treatment-for-bedwetting-in-children-and-young-people.xml&content=view-node%3Anodes-treating-recurrence
4. Onol FF, Guzel R, Tahra A Comparison of long-term efficacy of desmopressin lyophilisate and enuretic alarm for monosymptomatic enuresis and assessment of predictive factors for success: a randomized prospective trial. J Urol. 2015 Feb;193(2):655-61. doi: 10.1016/j.juro.2014.08.088. Epub 2014 Aug 23. PMID 25158273
5. Evans J, Malmsten B, Maddocks A, et al. Randomized comparison of long-term desmopressin and alarm treatment for bedwetting. J Pediatr Urol. 2011 Feb;7(1):21-9. doi: 10.1016/j.jpurol.2010.04.018. Epub 2010 Jun 25. PMID 20579938
6. Rittig N, Hagstroem S, Mahler B, et al. Outcome of a standardized approach to childhood urinary symptoms-long-term follow-up of 720 patients. Neurourol Urodyn. 2014 Jun;33(5):475-81. doi: 10.1002/nau.22447. Epub 2013 Jun 14. PMID: 23765698
7. Lottmann H, Baydala L, Eggert P, et al. Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational study. Int J Clin Pract. 2009 Jan;63(1):35-45. doi: 10.1111/j.1742-1241.2008.01956.x. PMID: 19125991
8. Wolfish NM, Barkin J, Gorodzinsky F, Schwarz R. The Canadian Enuresis Study and Evaluation--short- and long-term safety and efficacy of an oral desmopressin preparation. Scand J Urol Nephrol. 2003;37(1):22-7. PMID: 12745738
9. van Kerrebroeck PE. Experience with the long-term use of desmopressin for nocturnal enuresis in children and adolescents. BJU Int. 2002 Mar;89(4):420-5. Review. No abstract available. PMID: 11872036

Sep. 6, 2017Is metformin XL available? details
 

Response: Glumetza is an extended release metformin that is available. (2,3) It is not on Sask Drug Plan.(4)
References: 1. Canadian Pharmacist's Letter; December 2015; Vol: 31
2. DPD
3. PharmaClik
4. Sask online formulary

Sep. 7, 2017Is there any chance of cross reaction between fluconazole and nystatin? details
 

Medical Problems: Yeast infection (Vaginal)
Medication History: Fluconazole caused Hives
Response: Lexicomp and Micromedex do not state any cross reaction with Azole antifungals when reviewing Nystatin warnings/precautions. Additionally, fluconazole warnings state that cross reaction with other Azoles is not necessarily going to occur, but that caution should be used.
Looking at the chemical structure of each agent, there are no similar components that would lead to a hypersensitivity reaction.Therefore, it should be safe to use Nystatin.
References: 1. Lexicomp
2. Micromedex
3. Google image search

Sep. 7, 2017I have a patient on the Climara patch who has a sauna at home and is eager to use it. I understand that patients can have increased absorption from their fentanyl patch if they become fevered or hyperthermic. Do you know if there are similar concerns about altered absorption with estrogen patches? Would a sauna cause this to happen? details
 

Response: 1. While there is no direct data for the Climara patch, there does not seem to be a safety issue. All of the warnings around heat / saunas with the Climara patch has to do with the potential for the adhesion system to fail or loosen, thus decreasing the absorption of estrogen (1-3).

2. In general, heat will increase the absorption of transdermal patches (4), but with patches similar to Climara, it seems to have different results. A patch with estrogen/ levonorgestrel (ClimaraPro) exhibited slightly decreased absorption over 7 days when using a sauna for 10 minutes/day (unlikely to have clinical impact) (5); a patch with estrogen and norelgestromin showed no effect on drug absorption due to heat (6).

3. Thus, it will be safe for your patient to use a sauna while on the Climara patch, but repeated use of the Sauna during the same patch cycle will likely cause it to detach prematurely. With Climara, it's suggested by the manufacturer that a new patch needs to be put on if one falls off. Interestingly, the ClimaraPro patch allows patients to reuse a patch if it falls off. Both patches are identical, other than ClimaraPro has added progesterone. If the patch falling off does become an issue for the patient, I think it's reasonable for them to reuse their Climara patch.
References: 1. FDA product monograph for Climara: https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020375s026lbl.pdf
2. Technician Tutorial, The Ins and Outs of Transdermal Patches. Pharmacist’s Letter/Pharmacy Technician’s Letter. July 2017.
3. https://www.nps.org.au/medical-info/medicine-finder/climara-transdermal-patches
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841791/
5. https://www.ncbi.nlm.nih.gov/pubmed/23158806
6. https://www.ncbi.nlm.nih.gov/pubmed/11762557

Sep. 8, 2017Is Ciprodex appropriate for otitis externa in a woman 8 weeks pregnant? details
 

Patient Age: 29
Patient Sex: F
Medical Problems: otitis externa
Medication History: prenatal vits
Response: There have been no reports of undesirable side effects after topical use of quinolones during pregnancy. (1) Human Data Suggest Low Risk with oral ciprofloxacin use. (2)
References: 1. Schaefer C, Peters P, Miller RK, editors. Drugs during pregnancy and lactation: Treatment options and risk assessment. 3rd ed. San Francisco, CA: Academic Press; 2015.
2. Lexicomp Online - Ciprofloxacin (Briggs Drugs in Pregnancy and Lactation)

Sep. 11, 2017Does product of DIN 02376601 (Apotex Ibuprofen Capsules 400mg )contain gluten? It is for a patient with Celiac disease. details
 

Response: This product contains FD&C Green No. 3, gelatin, pharmaceutical ink, polyethylene glycol, potassium hydroxide, propylene glycol, purified water, sorbitol.(1) None of these ingredients are sources of gluten.(3) Furthermore, Apotex is a gluten-free manufacturer meaning ingredients in their products are not sources of gluten, though they do not test ingredients for traces of gluten that may have been picked up during production/shipping of the raw materials.(2)
References: 1. DPD - product monograph
2. http://www.apotex.com/ca/en/products/allergen.asp
3. Jade\Dz Files\24. General Files\Excipients\Gluten Cheat Sheet

Sep. 12, 2017How well does Prevacid (lansoprazole)capsule go through a feeding tube? We have tried Nexium (esomeprazole) tablets but the tube becomes plugged. details
 

Response: Some brands of esomeprazole tablets can be dispersed in water and administered through a 8-20 French feeding tube.(1) Apotex and Sivem should not be dispersed whereas Nexium, Ran, ACT, and Mylan can be dispersed.(4) Lansoprazole capsules can be opened and administered through a >16 French tube.(1) If this is a SK Health patient, MAC policy is in effect such that the drug plan will pay up to $0.20 per tablet/capsule; both lansoprazole and esomeprazole exceed these prices.(3) However, exemptions are made for both these products in patients who require feeding tubes.(3) Depending on the indication, the patient may qualify for EDS for esomeprazole and does qualify for EDS for pantoprazole (unable to swallow).(2) All of these PPIs are limited use benefit but no prior approval is required for NIHB.(5)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-AcidSuppression.pdf
2. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXA.pdf
3. http://formulary.drugplan.ehealthsask.ca/PDFs/APPENDIXC.pdf
4. PMs from DPD
5. NIHB 2017 Drug Benefit list

Sep. 12, 2017Our patient vomited his second dose of valacylovir within 10-15 minutes and he is worried about sub-therapeutic effect. I am worried about toxicity if he takes another dose. details
 

Medical Problems: adult
herpes labialis
no remnants of the tablets were seen in the vomitus but "couldn't really see much"
Medication History: valacyclovir 2g BID
Response: The rule of thumb is to redose drugs that have been vomited within 15 minutes of ingestion.(2) Little information is known about valacyclovir toxicity, but it is expected to be that of its active metabolite, acyclovir,which when ingested in overdose may cause only mild or moderate effects.(1) Persistent diarrhea was reported in patients receiving valacyclovir 2g QID.(1)
References: 1. Micromedex - Toxicology
2. Canadian Pharmacist's Letter; September 2009; Vol: 25

Sep. 13, 2017What treatment is best for glucocorticoid induced osteoporosis? details
 

Patient Age: 37
Patient Sex: F
Medical Problems: Breast Cancer Survivor (approx 5 years ago)
Ulcerative Colitis
On chronic oral steroid therapy, needing a bisphosphonate
Medication History: Azathioprine
Remicade
Simvastatin
Ranitidine
Solu-cortef infusions
Response: 1. Denosumab has no evidence for its use in glucocorticoid induced osteoporosis (GCIO) prevention (aside from indirect data from a 2008 study which showed it was better than placebo, but no comparisons to other treatments), thus it is not recommended in this case.

2. Bisphosphonates are the first-line recommendation. The official indication for glucocorticoid induced osteoporosis is once-daily dosage, but evidence shows once weekly or monthly should be equally effective. There is some evidence that zoledronic acid may be more potent than oral bisphosphonates in the setting of GCIO, so guidelines recommend zoledronic acid in high risk patients (defined as using >7.5mg prednisone equivalent per day for >3 months, and also a high risk FRAX score). However, if the patient is wanting to become pregnant at some point, use of zoledronic acid can be problematic. It can affect pregnancy outcomes even long after treatment completion, so it's typically not recommended to use in women of child bearing age.

3. Teriparatide would be another option. In some GCIO studies, it did increase bone mineral density (BMD) more than bisphosphonates (but actual fracture reduction unknown). Guidelines suggest teriparatide could be used in the highest risk patients who have had a fracture before. It is only covered by private insurance.
References: 1. UpToDate, Evaluation and treatment of premenopausal osteoporosis
2. Dynamed, treatment of glucocorticoid induced osteoporosis
3. ACR guidelines for treatment of glucocorticoid induced osteoporosis: http://onlinelibrary.wiley.com/doi/10.1002/acr.20295/abstract
4. Summary of guideline recommendations up to 2014: http://www.nature.com/nrrheum/journal/v11/n2/fig_tab/nrrheum.2014.188_T2.html
5. 2017 Malaysian guidelines: http://www.sciencedirect.com/science/article/pii/S2405525516300905

Sep. 13, 2017Our patient is wondering if he should be taking l-arginine. He has heard it is good for his heart because it relaxes the vessels, but has heard from others it may be harmful. Is it safe? Is it effective? Will it interact with any of his medications? He is currently taking ramipril, pravastatin, nitro spray, salbutamol, metoprolol, ASA 81 mg. details
 

Patient Age: 54
Patient Sex: M
Medical Problems: MI, stent in 2012
Medication History: ramipril, pravastatin, nitro spray, salbutamol, metoprolol, asa 81 mg
Response: Bottom line: the main reason for concern is that increased mortality has been reported from an RCT of 9g/day arginine following acute myocardial infarction (MI)(6); while this patient's MI was long ago and the effects seemed to be age related (>60 yr), there is not enough data about regular or long-term use of arginine in post-MI patients. That said, it may improve exercise tolerance though it is important to note this was a three day study.(8) Theoretically, he could experience additive hypotension when combined with his antihypertensives and could possibly increase potassium levels.(2)
------------------------
L-arginine has been promoted for cardiovascular disease on the premise that arginine is a cofactor in the synthesis of nitric oxide (1) and so if arginine is increased, so too should the production of nitric oxide.(1) As if often the case, this theory has not been borne out in clinical evidence.
An RCT of oral l-arginine for cardiovascular health was undertaken in patients with acute (within 21 days) MI (n=153) who were titrated to 9g/d for 6 months (or took placebo). The l-arginine group did not exhibit any improvements in left ejection fraction nor vascular stiffness; however, there were 6 deaths in the l-arginine group (8.6%) compared to none in the placebo group.(6) Nothing has demonstrated a benefit for reducing acute coronary events or CHD-related morality.(2) Another very small RCT (n=30) found no improvement of NO bioavailability in CAD patients on appropriate medical management.(7) Another RCT concluded arginine improved maximum exercise in patients with symptoms of stable angina and healed MI; however, this trial was in 22 participants over the course of three days.(8) One explanation to these findings is the arginine paradox in that exogenous arginine may eventually lead to more arginine destruction, eventually leading to impaired NO production.(4)
Due to the presumed, but not proven, vasodilatory effects of l-arginine, interaction with antihypertensives are often flagged.(1,2)
References: 1. Lexicomp
2. natural medicines
3. examine.com
4. To give or not to give? Lessons from the arginine paradox. Dioguardi FS. J Nutrigenet Nutrigenomics. 2011;4(2):90-8. doi: 10.1159/000327777. Epub 2011 May 28. Review. PMID: 21625171
5. https://www.hindawi.com/journals/omcl/2009/464523/abs/
6. Schulman SP, Becker LC, Kass DA, et al. L-arginine therapy in acute myocardial infarction. The vascular interaction with age in myocardial infarction (VINTAGE MI) randomized clinical trial. JAMA 2006;295:58-64.
7. Blum A, Hathaway L, Mincemoyer R, et al. Oral L-arginine in patients with coronary artery disease on medical management. Circulation. 2000;101(18):2160-2164

Sep. 14, 2017What is the safest antidepressant to use in someone taking linezolid chronically? details
 

Patient Age: 51
Patient Sex: M
Medication History: Linezolid 600mg BID
Amoxi Clav 875 TID chronic
Sulfatrim 800-160 TID chronic
Pantoprazole 40mg once daily
Atenolol 50mg once daily
Solifenacin 5mg once daily
Fluoxetine 20mg once daily…(take 1-4 caps once daily)
Response: 1. The actual risk of serotonin syndrome occuring due to combination of linezolid + SSRI is very low. The best estimate puts an absolute risk increase of 0.35% (0.54% incidence with SSRI + Linezolid, 0.19% incidence with just an SSRI)." However, due to the severity of the issue, and numerous case reports of toxicity, the manufacturers recommend not using the combination unless there is established need for both (benefit > risk) (1)

2. To lessen the risk, starting a person on a very low dose of an SSRI and titrating more slowly than usual reduces the risk (2). Also, citalopram and escitalopram seem to be the worst offenders of the drug interaction (DI) based on the case reports, but theoretically fluoxetine, fluvoxamine and sertraline would be expected to produce similar results, since they effect serotonnin levels similarly (3). Otherwise, bupropion has very little to no effect on serotonin. Venlafaxine has moderate effects. The TCAs have low to moderate effect. Mirtazapine has low to moderate effect.
Bupropion also has a different DI to be aware of: May cause hypertensive effect when mixed with drugs with MAO inhibition properties. Linezolid is a weak MAOI, so likely not an issue, but still requires monitoring. Contraindicated by US manufacturer; not a contraindication in Canada. Studies have been done with bupropion + more potent MAOIs: "There is little clinical evidence of serious problems when MAOIs and bupropion are given together" (1). Monitoring of blood pressure and making sure it is well-controlled prior to initiation would be reasonable. (1)
References: 1. Stockley's
2. UTD, serotonin syndrome
3. Handbook of Psych Meds online, neurotransmitter chart

Sep. 18, 2017We have a couple of patients that the doctor is wishing to taper off their narcotic medications. He has left it in our hands todetermine the taper with suggestion of 10% decrease of the total dose per week. Both patients are on hydromorphone and we were just wondering what is the best way to taper, especially if they are on both long and short acting. Is it preferable to keep them on both long or short acting or to get rid of the long or short acting first? Any advice would be much appreciated. details
 

Response: 1. If the patients are already on both short and long-acting opioids, then tapering the short-acting off first is best, since that is usually the more difficult part of the taper, which is made easier while the patient is on a long-acting formulation.

2. How fast to taper is variable, but a general suggestion is 5-10% per week of the initial total dose. So if they are on, for example, hydromorphone contin 36mg per day and hydromorphone IR 16mg per day, this is a total of 52mg hydromorphone per day, so the goal would be to reduce the dose by 5.2mg per week (round to 4mg per week to make it simpler with available dosage forms). Start by reducing 4mg/day per week off of the IR portion, and then continue with the long-acting at the same rate. With the hydromorphone contin dosage forms available, you'll have to do some additional rounding to make it work. Once the patient gets to 1/3 of their initial dose (18mg), they may need to taper even more slowly. When they get to the lowest dosage forms available, alternate day dosing will need to be done (eg. Hydromorphone contin 3mg BID one day, alternating with 3mg once daily).

3. Keep in mind this is just one suggestion, and if the patients feel like they can go faster, or would need to go slower based on past experience, that is fine. Also, a few references suggest that in some patients, switching everything over to a long-acting formulation may be easier if they have difficulty tapering off the short-acting portion.
References: 1. 2017 Opioid guidelines: http://nationalpaincentre.mcmaster.ca/documents/Opioid%20GL%20for%20CMAJ_01may2017.pdf
2. http://www.hrpub.org/download/201310/app.2013.010202.pdf
3. https://intermountainphysician.org/Documents/Opioid%20Tapering.pdf
4. https://anes-conf.med.umich.edu/opioidtaper/docs/combined_letters.pdf
5. https://fmf.cfpc.ca/wp-content/uploads/2016/11/T136848_An-Exit-Plan-for-Opioids_When-why-how.pdf

Sep. 19, 2017Can nebulized tobramycin be used for chronic exacerbations of COPD or pseudomonas aeruginosa eradication? What is the evidence for efficacy and safety? Is there data for optimal dose or duration? details
 

Patient Age: 77
Patient Sex: M
Medical Problems: COPD
Chronic pseudomonas infections
Many AECOPD per year / hospitilizations
Medication History: Long-term smoker
Response: 1. Nebulized tobramycin has not been well studied for use in COPD, but it is being increasingly used off-label despite this (1).
2. There are only two studies specifically looking at using inhaled tobramycin in COPD patients.
- Study (2):
- 13 patients resistant to oral and IV antibiotics with pseudomonas colonization
- Were givtobramycin nebulized 300mg twice daily for 14 days, and monitored periodically up to 6 month end point (no comparison group)
- The 6 month end point showed a reduction in pulmonary inflammation (via various markers) caused by pseudomonas, and pseudomonas aeruginosa colony density was lowered. Severe acute exacerbations were reduced by 42% compared to when the patient’s entered the study. This is a 42% relative risk reduction; unfortunately, the authors do not provide the baseline rate of exacerbations, so I cannot provide an absolute risk reduction or number-needed-to-treat.

- Study (3):
- 44 patients from Germany with severe COPD and pseudomonas colonization resistant to previous treatments. They were givetobramycin nebulized 80mg BID vs. placebo for 12 months. Their outcomes failed to reach statistical significance: “ Inhalation with 160 mg tobramycin by means of a nebuliser over a 12-month period did not reduce the number of hospitalisations for patients with severe COPD and a minimum of two hospitalisations compared to placebo.” However, their study was underpowered (they needed 80 patients to detect the difference they set out to study), and they had a high number of drop outs in both groups.

- Two literature reviews (4,5), the most recent being in 2017, conclude there is not sufficient evidence to use nebulized tobramycin in COPD patients. They only cite the two studies above.

3. Safety wise, the two studies above did not detect any issues, though they were not designed to assess safety. The study from Germany was monitoring for oto- and nephro-toxicity, and did not detect any issues. The only other safety data available will be from long-term Cystic Fibrosis trials. Given the patients in CF trials will be much younger than your patient, and their disease can confound the findings, it is difficult to extrapolate the data.
But:
- This study (6) used nebulized tobramycin for 1 month; tinnitus was a significant occurrence, but no ototoxicity or permanent hearing issues, or nephrotoxicity.
- This study (7) used nebulized tobramycin for 2 months; “No clinically significant changes in chemical or hematologic laboratory parameters or vital signs occurred during either phase of the study. During the core, audiometric findings of hearing thresholds >20 dB were rare, occurring in three (1.9%) and two (1.2%) of [low dose tobramycin] and [higher dose tobramycin] patients, respectively, at week 4 and two patients each, 1.3% and 1.2% for [low dose tobramycin] and [higher dose tobramycin] patients, respectively, at week 8. Hearing thresholds of >20 dB were experienced in three patients and one case of drug-related but mild hypoacusis were reported during the extension."
- In the product monograph, they report on a 6 month trial in CF patients. The only side-effects greater than placebo were voice alteration and tinnitus, which all resolved upon drug discontinuation.

4. In summary, evidence does not favour efficacy. Existing evidence is conflicting, and based on small, low quality trials. Optimal dose and duration is also unknown. Safety wise, based on CF studies it seems safe for long-term use, but extrapolation from CF patients to COPD patients may not be accurate.
References: 1. http://thorax.bmj.com/content/thoraxjnl/early/2016/05/10/thoraxjnl-2015-208145.full.pdf
2. https://www.ncbi.nlm.nih.gov/pubmed/18821068
3. https://www.ncbi.nlm.nih.gov/pubmed/23836249
4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4028738/
5. www.mdpi.com/1422-0067/18/7/1344/pdf
6. https://www.ncbi.nlm.nih.gov/pubmed/11568993
7. https://www.ncbi.nlm.nih.gov/pubmed/24464974

Sep. 19, 2017Are there any studies that show olanazapine 5mg at bedtime would help with nausea/vomiting caused by chemotherapy? This patient has previously used Zofran, Maxeran, Gravol, steroids, and Ativan to little success. details
 

Patient Age: 32
Patient Sex: M
Response: 1. There is fairly robust evidence to support olanzapine's use in severe nausea and vomiting in those on chemotherapy. It can be used by itself or in addition to the other treatments.
- This RCT (1) tested olanzapine 5-10mg + ondansetron vs. placebo + ondanestron in those on highly emetogenic cisplatin or doxorubicin chemotherapy. Olanzapine significantly increased the complete response rate (no emesis, no nausea) during all 3 phases (85.7% vs 64.6%, acute phase (0-24h after chemo); 66.9% vs 52.4%, delayed phase (25-120h after); 63.6% vs 40.6% overall phase)
- This meta-analysis (2) compared olanzapine 5-10mg vs. ondansetron. In the overall phase significantly improved the likelihood of no emesis by 41% and no nausea by 53%. In the acute phase (0 to 24 hours after chemotherapy), olanzapine 5 or 10 mg significantly improved the likelihood of no emesis by 10%, and olanzapine 10 mg significantly improved no emesis by 10% and no nausea by 5%. In the delayed phase (24 to 120 hours after chemotherapy) olanzapine 5 or 10 mg significantly improved the likelihood of no emesis by 31% and no nausea by 50%
- In another literature review (3) in children, they found essentially the same findings as the studies above. Olanzapine was added to ondansetron in most cases.
- Finally, the American Society of Clinical Oncology clinical practice guidelines (4) recommend adding olanzapine to a patient's anti-emetic regimen, if it is not working. They further add that benefit of olanzapine is most beneficial during the first week after chemotherapy.
References: 1. https://www.ncbi.nlm.nih.gov/pubmed/27410922?dopt=Abstract
2. https://www.ncbi.nlm.nih.gov/pubmed/26768437?dopt=Abstract
3. https://www.ncbi.nlm.nih.gov/pubmed/25328089?dopt=Abstract
4. https://www.ncbi.nlm.nih.gov/pubmed/21947834?dopt=Abstract

Sep. 21, 2017Our patient just had knee surgery and is taking hydromorphone 4 mg every 4 hours and Xarelto. Is it safe to start taking medical marijuana (3g QID CBD (cannabidiol) oil under her tongue)? details
 

Medication History: zopiclone
Eltroxin
Xarelto
Response: There is little information on drug interactions with medical marijuana. References that distinguish the cannabidiol (CBD) component (which lacks psychoactive effects at therapeutic doses [1]) from the tetrahydrocannabinol (THC) component do not flag an interaction with hydromorphone (2) except that high doses of CBD may cause additive CNS depression.(1)
As for the Xarelto, there are no hematologic adverse effects reported of CBD (1,2) nor any interactions flagged with antithrombotic agents (1,2); however, there has not been as much rigorous research to understand the kinetics/interactions of CBD to be able to discount an interaction altogether.
References: 1. Natural Medicines
2. Lexicomp
3. drugcocktails.ca

Sep. 21, 2017How does Voltaren Rapide (diclofenac potassium) compare to the regular Voltaren (diclofenac sodium)? details
 

Response: The differences are time to maximum concentration (and therefore onset of effect):[ diclofenac potassium: tablet 20-60 min; oral solution 10-15 min; diclofenac sodium: EC tablet 2h; SR tablet 4h.] and indications: diclofenac potassium: tablet - Mild-moderate pain that may be accompanied by inflammation for up to 7 days; solution - acute migraine; diclofenac sodium (EC and SR): rheumatoid arthritis and osteoarthritis. (1) Beyond absorption everything is the same as the diclofenac will have dissociated from its salt.
References: 1. RxTx - CPhA NSAID monograph

Sep. 27, 2017Prescriber who is a specialist in hormone therapy has prescribed 100 mg delatestryl every week. I have found the interval is normally every 2 weeks or even longer. Is once weekly dosing safe? details
 

Patient Age: 38
Patient Sex: M
Response: Treatment of male hypogonadism with doses of 75-150 mg testosterone enanthate every 7-10 days has been advocated by some to more closely resemble physiological levels and reduce fluctuations; of course, this is less convenient.(3) As such, if the patient is being treated for hypogonadism, this dose is reasonable.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-Androgens.pdf
2. Lexicomp
3. AHFS DI

Sep. 28, 2017It is established that Depo-provera can cause bone mineral density (BMD) loss, but what about the progestin-only pill Micronor? Why the difference in risk? details
 

Response: 1. The mechanism through which depo causes BMD loss is that medroxyprogesterone is a potent anti-estrogen, leading to decreased estrogen levels / activity, potentially causing a sub-clinical hypo-estrogenic state which is associated with BMD loss (1). The mini-pill (norethindrone acetate 0.35mg) has not been found to cause BMD loss, but there is only one small study available that investigates this (2,3). This study was in lactating women, but found that the mini-pill preserved or boosted BMD vs. no treatment. I doubt this should be extrapolated to a non-lactating population. The CDC concludes that oral POCs will not cause a BMD issue (5).

2. Theoretically, the difference in risk potential could be explained by their pharmacokinetics. Medroxyprogesterone acetate has potent anti-estrogen activity, whereas norethindrone acetate seems to have little or no anti-estrogen activity (4,6), or may actually have weak positive estrogenic effects, estimated to be around 5-10 mcg of ethinyl estradiol (6). Medroxyprogesterone also has weak glucocorticoid effects, which could be partially responsible for the BMD loss, but norethindrone has no glucocorticoid activity (6).

The summary table at http://www.tandfonline.com/doi/pdf/10.1080/13697130500148875?needAccess=true (6) shows the receptor differences (note that Norethisterone is the same as norethindrone).
References: 1. http://www.cmaj.ca/content/172/6/746.full
2. http://www.medscape.com/viewarticle/743769_4
3. https://www.ncbi.nlm.nih.gov/pubmed/16627031
4. https://www.drugbank.ca/drugs/DB00603
5. https://www.cdc.gov/reproductivehealth/contraception/mmwr/mec/appendixc.html
6. http://www.tandfonline.com/doi/pdf/10.1080/13697130500148875?needAccess=true

Sep. 29, 2017Our patient has extensive vitiligo and I am wondering if monobenzo ether of hydroquinone is available for permanent depigmentaion? details
 

Response: Monobenzyl ether of hydroquinone also goes by monobenzone ethyl ester(2), monobenzone(5), benzyl hydroquinone (6). It is different from hydroquinone (3,5,6) in that it often causes permanent depigmentation (5,6); it is used at a concentration of 20% for disseminated vitiligo. (1,5,6) A product, Benoquin 20%, had been available in Canada but was discontinued in 2014. (2) I checked with compounding pharmacies and they are not able to order the active ingredient.(10) In terms of depigmentation agents, the only other product I found, menoquin(1), was available as a combination product with tretinoin but has also been discontinued (8) and is not available to compound.
References: 1. Dynamed - Vitiligo- Depigmentation medications
2. DPD
3. Br J Dermatol. 2013 Jan;168(1):5-19. doi: 10.1111/j.1365-2133.2012.11197.x. Epub 2012 Nov 2. Guidelines for the management of vitiligo: the European Dermatology Forum consensus. Taieb A1, Alomar A, Böhm M, et al. PMID: 22860621
4. Lexicomp
5. Martindale's
6. AHFS
7. medisca.com
8. https://www.drugbank.ca/drugs/DB09516
9. UTD - Vitiligo: Management and prognosis
10. Email communication with Janice, Hill Ave Drugs - Hillavedrugs@accesscomm.ca, 29 Sep 2017

Sep. 29, 2017Scenario: a child (3 year old) had the varicella vaccine and then approximately 1 to 2 weeks later the parent who is 31 came down with varicella zoster, even though he claims he never had chicken pox. Could his contact with the child who was just vaccinated have caused this in some way? details
 

Patient Age: 31
Patient Sex: M
Response: Transmission of varicella zoster virus (VZV) from recently vaccinated persons to unvaccinated persons is rare, but has been reported; a more common scenario is transmission to vulnerable contacts of immunocompromised patients who develop a rash following vaccination.(2) As herpes zoster is reactivation of latent VZV(1), shingles is always preceded by chickenpox (though the chickenpox may not be recognized). While it is possible the adult developed chickenpox from the child, shingles does not develop from primary VZV infection and if the adult has indeed developed shingles, it is from previous VZV infection, making this a coincidence.
References: 1. UTD - Epidemiology and pathogenesis of varicella-zoster virus infection: Herpes zoster
2. UTD - Vaccination for the prevention of chickenpox (primary varicella infection)
3. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-24-varicella-chickenpox-vaccine.html#p4c23a10
4. https://www.cdc.gov/chickenpox/about/transmission.html
5. http://www.bcmj.org/articles/herpes-zoster-eruption-associated-vaccine-strain-varicella-zoster-virus-case-report
6. https://www.livescience.com/45804-chickenpox-vaccine-cause-shingles.html

Oct. 3, 2017There has been a medication error at our nursing home. Arthrotec instead of voltaren was in the patient's blister. We are going to meet Thursday morning and I want to know the implications of a pregnant or non-pregnant person touching the tablets for 5-15 days (wasn't sure of the duration). details
 

Response: Diclofenac is not on the National Institute for Occupational Safety and Health (NIOSH) list.(1) Misoprostol is only on because of pregnancy so if pregnancy is not an issue, this is not an issue. Even at that, the only recommended personal protective equipment recommended (from Table 5) when administering intact tablets from unit-dose packaging is single-layer gloves so if that’s how these were administered by anyone pregnant or potentially pregnant, no further recommendations would have been otherwise made. (1)
References: 1. https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf
2. eCPS

Oct. 4, 20171. I have a young, healthy 23 year old woman who has been o Micronor for a few years. She has no contraindications to Combined Oral Contraception (COC). She reports she was started on the minipill initially as a form of contraception and has never had problems so she continues. Is there any risk of her continuing this medication long term and would there be benefits of COC over Progestin only Pill (POP) for her? What about risk of bone density loss for her? a. She has no medical history b. She is not obese c. Non smoker d. Paternal grandma and maternal grandma history of breast cancer e. She takes it everyday at the exact same time details
 

Patient Age: 23
Patient Sex: F
Medical Problems: None
non-smoker
hx breast cancer in grandmothers
Medication History: Micronor
Response: If she is happy with this form of contraception and maintains her adherence, there is no reason to change. The biggest reasons the progestin-only pill (POP) is not favoured by many women are that it tends to cause irregular bleeding (3,4) and of course requires the strict adherence.(4) Should she conceive, there is a higher risk of it being ectopic, possibly because of impaired ciliary function.(2,4) To be clear, taking the POP does not increase her risk of ectopic pregnancy from that of a women not using contraception but if there is POP failure, a higher proportion of women using POP would have an ectopic pregnancy than those failing from other methods.(2) No concern has been raised about reduced BMD from the POP(1-4), likely because lowered estrogen levels are not associated with POP as they are with DMPA.

Potential advantages of a combined hormonal contraceptive are more regular bleeding patterns, improvement of acne (which may not necessarily be increased with POP but if acne is a problem, the POP won’t help it), and a more forgivable adherence need.(1) I can’t think of a compelling non-contraceptive benefit of the combined oral contraceptive that would prompt me to suggest a switch.
References: 1. RxTx - Contraception
2. SOGC - Canadian Contraception Consensus (Part 3 of 4): Chapter 8 e Progestin-Only Contraception 2016
3. Contraception and Sterilization. In: Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. eds. Williams Gynecology, 3e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=1758§ionid=118167533. Accessed October 05, 2017.
4. Books @ OVId - Clinical Guide for Contraception, A > Table of Contents > 3 - Special Uses of Oral Contraception: Emergency Contraception The Progestin-Only Minipill

Oct. 4, 2017 I have a 46 year old, sexually active woman who is on progestin injectio(depo-medroxyprogesterone DMPA) for contraceptive management. She has been on it for 20+ years. She has no menopausal symptoms. She is ammenorheic. What are the risks of her continuing this medication for such a long term? Are there other associated risks of her being on this going into the perimenopausal phase? Bone density? details
 

Response: The concerns of reduced Bone Mineral Density (BMD) may have been overstated somewhat by the FDA.(4) Indeed, DMPA is associated with reduced BMD with most occurring in the first two years and leveling off thereafter.(2,3) To date there is no strong evidence to suggest DMPA causes osteoporosis (2,4) or increases the risk of fracture.(2) Furthermore, the bone loss is reversible, usually within 5 years after discontinuation.(1,2) Given your patient may be approaching menopause, she may want to consider discontinuing DMPA at this point to give her an opportunity to reverse as much bone loss as possible before she enters menopause. Please know this is not supported by evidence but is merely a pragmatic approach. Regardless of her decision, I would encourage her to maintain good bone health (appropriate calcium/vitamin D intake, undertake weight-bearing exercise, no smoking, limit caffeine intake) (2).
References: 1. RxTx - Contraception
2. SOGC - Canadian Contraception Consensus (Part 3 of 4): Chapter 8 e Progestin-Only Contraception 2016
3. Contraception and Sterilization. In: Hoffman BL, Schorge JO, Bradshaw KD, Halvorson LM, Schaffer JI, Corton MM. eds. Williams Gynecology, 3e New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=1758§ionid=118167533. Accessed October 05, 2017.
4. Books @ OVId - Clinical Guide for Contraception, A > Table of Contents > 6 - Injectable Contraception

Oct. 5, 2017Lung cancer patient has been getting cisplatin/etoposide followed by dexamethasone/ondansetron (next day). He has BPH and the last two cycles he has had to catheterize himself (he's a nurse) because of BPH flare. He is sure it's from the dexamethasone but I can't find anything to support. Can you look to see if this has been reported with dexamethasone or his other meds? details
 

Patient Sex: M
Medical Problems: BPH
lung cancer
Medication History: cisplatin/etoposide Oct 2; dexamethasone Oct 3 (catheter until Sunday) ondansetron starts the 3rd.
Flomax, hydromorphone (not sure if taking), bupropion, pantoprazole, zopiclone
Response: Ondansetron has a 5% incidence of urinary retention.(1) Since he starts the dexamethasone the same day as ondansetron, this seems to be the most likely culprit.
References: 1. Lexicomp Online
2. Micromedex

Oct. 5, 2017The patient is being treated with isoniazid 350mg (dose increase due to interaction with systemic steroid)/rifampin 600mg /pyrazinamide 1500mg/pyridoxine 25mg and moxifloxacin once daily- as well as prednisone 60mg once daily. Ethambutol is not being used at this time. Is there evidence for using moxifloxacin 800mg and if so is there a benefit to using this dose over moxifloxacin 400mg once daily? details
 

Patient Age: 28
Patient Sex: F
Medical Problems: Potential TB meningitis
64 kg
Medication History: INH 350 mg, rifampin 600 mg, pyrazinamide 1500 mg, pyridoxine 25 mg moxifloxacin
prednisone 60 mg
Response: Other than case reports of use of moxifloxacin 800 mg PO OD for TB meningitis, I found one phase II open-label trial. (1) This trial certainly was limited in size—it enrolled 60 patients who were randomized into 6 different arms: {PO rifampin 450 mg + [no moxi] + [400 mg PO moxi] or + [800 mg PO moxi]}, {IV rifampin 600 mg + [no moxi] + [400 mg PO moxi] or + [800 mg PO moxi]}. Other treatment given to the patients included standard-dose isoniazid, pyrazinamide and adjunctive corticosteroids. The patient population and resources differ from here: this study took place in Indonesia and the median BMI of patients was 18.4. The authors measured CSF levels up to 6h post dose and reported the Cmax as well as clinical outcomes.

In terms of clinical outcomes of the study above, there was no statistically significant difference in death rates among the different arms of moxifloxacin; however, numerically, the 800 mg group had a higher death rate (63%) compared to the 400 mg group (42%) and the no moxi group (45%). There had been a statistically significant finding between the rifampin groups in that the death rate of the 450 mg PO group was 65% compared to 34% in the IV group (p=0.03). Severe cardiotoxicity was not reported in any patients. Mild QTc prolongation (not defined by the authors) occurred in 36.8% on moxi 800 mg, 31.6% of moxi 400 mg and 22.7% of no moxi.

In the moxifloxacin groups, the Cmax in the CSF was 2.43 mg/L (1.81-3.27) in those receiving 800 mg and 1.52 mg/L (1.28-1.82) for those receiving 400 mg. MIC was not reported but others report MIC of 0.12 to 0.25 mcg/ml.2,3,4 As such, it seems an 800 mg dose may not be necessary. However, WHO reports that for multidrug-resistant isolates there is little resistance with concentrations of 2 mcg/ml compared to 0.9% to 14.6% resistance at 0.5 mcg/ml 5; keep in mind this is worldwide and a North American study determined MIC of 0.12 to 0.25 mcg/ml for multi-drug resistant isolates.2 I will note that one author has made the observation other studies have not demonstrated a clear dose-concentration relationship regarding moxifloxacin in plasma or CSF.6
References: References:
1. Ruslami R, Ganiem AR, Dian S, et al. Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2013 Jan;13(1):27-35.
2. Mpagama SG, Ndusilo N, Stroup S, et al. Plasma drug activity in patients on treatment for multidrug-resistant tuberculosis. Antimicrob Agents Chemother. 2014;58:782–788.
3. Isaeva Y, Bukatina A, Krylova L, et al. Determination of critical concentrations of moxifloxacin and gatifloxacin for drug susceptibility testing of Mycobacterium tuberculosis in the BACTEC MGIT 960 system. J Antimicrob Chemother 2013; 68(10):2274-2281.
4. https://www.publichealthontario.ca/en/eRepository/LAB_SD_083_Mycobacterium_tuberculosis_MTB_susceptibility_testing.pdf
5. http://www.who.int/tb/publications/global_report/gtbr2016_main_text.pdf?ua=1
6. Ukwaja KN, Onyedum CC. Rifampicin and moxifloxacin for tuberculous meningitis. Lancet Infect Dis. 2013 Jul;13(7):569-70.

Oct. 10, 2017Patient presenting to the hospital with new onset confusion and delirium. Has been stable on home meds since recent admission (discharged 2 weeks prior). On admission his baclofen was decreased from 20 mg po BID to 10 mg po BID, his lorazepam was discontinued and his oxybutynin held. Minimal improvement was noted with reductions to chronic home medications. Doctor is concerned that he might be experiencing ciprofloxacin induced delirium as this is the only change from his past admission. Please look into the incidence of this as it is not a common adverse effect of ciprofloxacin that I am aware of. details
 

Patient Age: 62
Patient Sex: M
Medical Problems: Chronic sacral ulcer with Left ischium osteomyelitis - wound cultures have grown pseudomonas, MSSA, GBs.
Was recently discharged from hospital and has no new medication changes. Patient has been paraplegic x 14 years and uses a catheter. Now presenting to hospital for new onset confusion with no previous psych history.
Allergies: morphine (bizarre behavior), gentamycin (rash/hives), ceftazidime (rash/hives)
Medication History: Ciprofloxacin 750 mg po BID (started Sept 20th), Cefazolin 2 G IV Q8H (home IV)
Tinzaparin 4500 units sc daily
Baclofen 10 mg po BID, Lorazepam 0.5 mg po daily, Oxybutinin 5 mg po BID, Pregabalin 150 mg po daily, Rabeprazole 20 mg po daily , Acetaminophen 650 mg po QID
Response: As you know, delirium is not a common adverse reaction of ciprofloxacin, but it has been reported. (1,2) In one review article, the authors wrote: For some CNS adverse events, such as delirium or psychosis, the majority of patients had no underlying diseases or concomitant medication that could induce/precipitate the development of delirium or psychosis. There were also cases showing positive dechallenge, where patients recovered within 1 day following drug withdrawal. Moreover, the events developed within a few days after starting the quinolone.(2)
Normally I would have expected a lot of overlap between the data collected for the retrospective study of 4189 in Micromedex and the review article; however, the study cited in Micromedex was published in a German journal (3) and I assume in German so it is possible there is little overlap of cases (but I can’t be sure of this).
References: 1. DrugDex
2. Tomé AM, Filipe A. Quinolones: review of psychiatric and neurological adverse reactions. Drug Saf. 2011 Jun 1;34(6):465-88. doi: 10.2165/11587280-000000000-00000. Review.
PMID: 21585220
3. Hollweg M, Kampfhammer HP, Krupinski M, et al: Psychopathologische Syndrome unter Behandlung mit Gyrasehemmern. Nervenarzt 1997; 68:38-47.

Oct. 10, 2017This patient is now CTC and the team is hoping to use some of the common end of life care drugs to keep him comfortable (scopolamine patch, haloperidol, methotrimeprazine and dilaudid). Will any of these agents cause a worsening of myasthenia gravis and are there any concerning drug interactions that would be clinically relevant in a terminally ill patient with a life expectancy of a few months? Are there any other agents you would recommend? details
 

Patient Age: 85
Patient Sex: M
Medical Problems: Myasthenia gravis
brain metastases (primary tumor location unknown)
allergies: penicillin (rash/hives), sulfa (rash/hives)
Medication History: dexamethasone, gravol, phenytoin,
glycopyrrolate, hypromellose eye drops, pyridostigmine
Tylenol, midazolam, rabeprazole
Response: Myasthenia gravis (MG) is a condition affecting the nicotinic cholinergic receptors and most anticholinergic agents used in palliative care are selective for muscarinic sites.(1) In vitro studies have suggested scopolamine and glycopyrrolate are highly selective for the muscarinic receptor.(1-3) Selectivity will vary among anticholinergics and may be compromised with higher doses and/or combinations of more than one anticholinergic.(1) Palliative Care Formulary recommend antimuscarinics be used with caution in patients with MG.(4)

Of the drugs you mentioned, haloperidol has been found to impair neuromuscular transmission in experimental settings (5) but it is also on a list of drugs that are “usually well-tolerated in myasthenia gravis but occasionally associated with an exacerbation.”(6) Similar to this is phenytoin in which effects on neuromuscular transmission in vitro have been reported (5) but it also appears on the same list as haloperidol.(6)

There are some concerns not directly related to ACh transmission. Because MG may result in respiratory depression due to weakening of the diaphragmatic muscles, respiratory depressants need to be used with caution; this includes opioids and benzodiazepines.(2,4,5)

Corticosteroids can cause MG exacerbation when high doses are initiated.(5) I’m sure this has already been sorted out with the dexamethasone on board but just something to keep in mind should a significant increase in dose be considered in the future.

There is a case report of a patient with MG who was experiencing distress because of both bronchial and hypopharyngeal secretions. The team was unsure if this was due to the pyridostigmine on board and conversely, if treating with an anticholinergic (as they typically did for this symptom) would cause deterioration in her MG. Pyridostigmine dose was reduced with no effect so the team cautiously started transdermal scopolamine and morphine, which was not reported to cause worsening of MG, her secretions improved and she died comfortably 4 days later.(1)

Essentially, no drugs are completely contraindicated but the main concerns are those with anticholinergic effects (though clearly these can be used) and those that may contribute to respiratory depression. These drugs can be used but need to be introduced at low doses, titrated slowly with close patient monitoring.
References:
References:
1. Speiss J, Scott S. Anticholinergic agents for the treatment of “death rattle” in patients with myasthenia gravis. J Pain Symptom Manage. 2003; 26(1):684-686
2. Haroutiunian S, Lecht S, Zur A, et al. The challenge of pain management in patients with Myasthenia Gravis. J Pain Palliat Care Pharmacother. 2009; 23(3): 242-60
3. Nair V, Hunter J. Anticholinesterase and anticholinergic drugs. CE in Anaesthes Crit Care Pain. 2004;4(5):164-168
4. Twycross R, Wilcock A, Howard P. editors. Palliative Care Formulary. 5th ed. Nottingham: Hayward House Study Centre; 2014.
5. Mehrizi M, Fontem R, Gearheart T, et al. Medications and Myasthenia Gravis (A reference manual for health care professionals). Myasthenia Gravis Foundation of America. [Aug 2012; cited 11 Oct 2017]. Available at http://www.myasthenia.org/portals/0/draft_medications_and_myasthenia_gravis_for_MGFA_website_8%2010%2012.pdf
6. Bird S. Clinical manifestations of myasthenia gravis. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 11 Oct 2017. Available from www.uptodate.com Subscription and login required

Oct. 10, 2017Ceftriaxone injection and azithromycin 2g oral stat dose; are these safe in lactation? details
 

Medical Problems: chlamydia/gonorrhea
infant 30 days old, otherwise healthy
Response: Both drugs are excreted in small quantities into the milk.(1,2) The dose received by infants of azithromycin via milk is much lower than the pediatric dose.(2) While ceftriaxone is not normally given directly to infants, its low oral bioavailability further reduces any systemic exposure.(2) No adverse effects via milk have been reported in infants from either drug but monitor for vomiting/diarrhea/rash.(1,2)
References: 1. LactMed
2. Hale

Oct. 10, 2017My sister is being treated for the above diagnosis and is currently on IV ceftriaxone 2gm QD and oral metronidazole 500mg BID. The hospital has discharged her to her community pharmacy but she cannot afford the cost of the IV ceftriaxone ($1500/month). Is there another cheaper option available that would be just as effective to treat her disease? details
 

Patient Age: 35
Patient Sex: F
Medical Problems: complex zoonotic disease syndrome with extensive neuroinvasive symptomatology
organism: babesia and bartonella bacteria
Symptoms: headaches (chronic prior to meds), dizziness, nausea, (did have diarrhea for over a month), gi cramping, ear pain/tinnitus, eye pain, trigeminal nerve pain, neck cramp, hip pain, intermittent shortness of breath and chest pain, loss of weight, extreme lethargy/malaise, muscle cramping, increased sense of taste and smell, insomnia, anxiety and depression
Response: Bottom Line: I found some potential alternatives but they require more frequent dosing and are more expensive than the ceftriaxone. This is mainly based on the assumption that IV antibiotics are required, which should be confirmed. I did find Sterimax ceftriaxone to be significantly less expensive than other brands if this is not the brand your sister is already receiving.
Babesia is a protozoa transmitted primarily by ticks and Babesia microti is the primary species in North America.(1-3) Usual treatment for mild to moderate disease is oral azithromycin + oral atovaquone.(1-3) This is the same treatment for severe disease, except the azithromycin is administered IV. An alternative regimen in severe disease is IV clindamycin + oral quinine.1-3 I did not find that metronidazole is typically used for babesiosis (1-3) nor is babesia listed in its spectrum (4); however, because it is active against protozoa, (4) I am guessing the metronidazole is on board because of the babesia.
Bartonella is a gram negative bacilli that can cause cat scratch disease (4-6); this infection is usually self-limited (4,7) but can result in visceral organ, neurologic, and ocular manifestations.(7) Typical antibiotic regimens include azithromycin,(4,5,7) clarithromycin, (5,6) erythromycin, (4) doxycycline,(4,5) chloramphenicol,(4) rifampin,(4-6) trimethoprim/sulfamethoxazole,(4-6) gentamicin (4) and ciprofloxacin. (4-6) That said, ceftriaxone is active against Bartonella and has been used in combination with an oral macrolide.(4)
I found a case report in which ceftriaxone was given in combination with rifampin for meningitis caused by Bartonella henselae.(8) Ceftriaxone was chosen based on its proven efficacy in meningitis due to susceptible organisms. Given your sister’s neurologic diagnosis, I am left to believe the ID team feels CNS penetration is required and, at least in the case of meningitis, all patients should be treated with IV antibiotics because oral antibiotics rarely achieve the necessary CNS concentrations.(9)
For the various antibiotics reported to be active against Bartonella I looked for CNS penetration and IV availability. TMP-SMX penetrates well,(10) ciprofloxacin has variable penetration so should only be used based on the MIC of the bartonella,(10) azithromycin and erythromycin do not produce adequate CSF concentrations,(4) gentamicin penetrates poorly,(10) and chloramphenicol penetrates well but is not recommended due to failure rates and increased mortality.(10)
As such, the potential alternative agents would be ciprofloxacin (depending on MIC) and TMP-SMX. The dose of IV ciprofloxacin for meningitis is 400 mg IV q8h4 and the dose of TMP-SMX is 160-24 TMP/800-1200 mg q12h.(11) The fact these drugs are q8-12h certainly reduces convenience; more importantly, the daily price of these is much more expensive than ceftriaxone. (Daily costs based on acquisition cost only: $110 for Cipro; $310-465 for TMP-SMX compared to $26-51 for ceftriaxone calculated in the same way).(12) I’m not sure why, but Sterimax ceftriaxone 10x1g (DIN 02325616; McKesson item #5503) is listed at $133 whereas the Teva and Sandoz brands are $253.47. McKesson says there is stock of the Sterimax brand. If your sister is not currently receiving this brand perhaps look into this? I feel I must be missing something though.
Clearly the crux of my research has been based on the assumption that the antimicrobial therapy needs to penetrate the CNS (and therefore it must be IV). Because this is a significant assumption, and your sister’s regimen is so expensive, I think it’s important for her or you on her behalf to talk to the ID team about potential alternatives or at least to confirm the reason ceftriaxone has been chosen.
References:
1. Krause P and Vannier E. Babesiosis: Treatment and prevention. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
2. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - 2017. Record No. 114053, Babesiosis; [updated 23 Aug 2017, cited 12 Oct 2017]; [about 12 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=114053 Registration and login required.
3. Red Book 2015 Report of the Committee on Infectious Diseases BOOK ONLINE. Jackson, WY, Teton Data Systems, 2017: Based on: American Academy of Pediatrics. Babesiosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015 STAT!Ref Medical Reference Library. Accessed 12 Oct 2017.
4. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 12 Oct 2017.
5. Red Book 2015 Report of the Committee on Infectious Diseases BOOK ONLINE. Jackson, WY, Teton Data Systems, 2017: Based on: American Academy of Pediatrics. Cat-scratch disease. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015. STAT!Ref Medical Reference Library. Accessed 12 Oct 2017.
6. Tsuneoka H, Yanagihara M, Nojima J, et al. Antimicrobial susceptibility by Etest of Bartonella henselae isolated from cats and human in Japan. Ichihara K. J Infect Chemother. 2010 Dec;16(6):446-8.
7. Spach D and Kaplan S. Treatment of cat scratch disease. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
8. McGrath N, Wallis W, Ellis-Pegler R, et al. Neuroretinitis and encephalopathy due to Bartonella henselae infection. Aust N Z J Med. 1997 Aug;27(4):454.
9. Tunkel A. Treatment of bacterial meningitis caused by specific pathogens in adults. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
10. Friedman N and Sexton D. Gram-negative bacillary meningitis: Treatment. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
11. Product monograph for Septra Injection. Aspen Pharmacare Canada Inc. Toronto, ON M5C 2S2. 11 Jan 2017.
12. McKesson Canada. PharmaClik [Internet]. 2017 [cited 12 Oct 2017]. Available from http://clients.mckesson.ca Account required.
References: References:
1. Krause P and Vannier E. Babesiosis: Treatment and prevention. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
2. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - 2017. Record No. 114053, Babesiosis; [updated 23 Aug 2017, cited 12 Oct 2017]; [about 12 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=114053 Registration and login required.
3. Red Book 2015 Report of the Committee on Infectious Diseases BOOK ONLINE. Jackson, WY, Teton Data Systems, 2017: Based on: American Academy of Pediatrics. Babesiosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015 STAT!Ref Medical Reference Library. Accessed 12 Oct 2017.
4. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 12 Oct 2017.
5. Red Book 2015 Report of the Committee on Infectious Diseases BOOK ONLINE. Jackson, WY, Teton Data Systems, 2017: Based on: American Academy of Pediatrics. Cat-scratch disease. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015. STAT!Ref Medical Reference Library. Accessed 12 Oct 2017.
6. Tsuneoka H, Yanagihara M, Nojima J, et al. Antimicrobial susceptibility by Etest of Bartonella henselae isolated from cats and human in Japan. Ichihara K. J Infect Chemother. 2010 Dec;16(6):446-8.
7. Spach D and Kaplan S. Treatment of cat scratch disease. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
8. McGrath N, Wallis W, Ellis-Pegler R, et al. Neuroretinitis and encephalopathy due to Bartonella henselae infection. Aust N Z J Med. 1997 Aug;27(4):454.
9. Tunkel A. Treatment of bacterial meningitis caused by specific pathogens in adults. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
10. Friedman N and Sexton D. Gram-negative bacillary meningitis: Treatment. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 12 Oct 2017. Available from www.uptodate.com Subscription and login required
11. Product monograph for Septra Injection. Aspen Pharmacare Canada Inc. Toronto, ON M5C 2S2. 11 Jan 2017.
12. McKesson Canada. PharmaClik [Internet]. 2017 [cited 12 Oct 2017]. Available from http://clients.mckesson.ca Account required.

Oct. 13, 2017I have a patient who is requesting the Shingles vaccination, but she has RA and is on 25mg weekly of methotrexate. I’m not sure if this qualifies as “immunosuppression”. Her WBCs are normal on her lab work. details
 

Medication History: Methotrexate 25 mg weekly
Response: Specifically related to the shingles vaccine, a threshold dose >0.4 mg/kg/week MTX is considered immunosuppressive.(1) If your patient weighs <62.5 kg you and she may want to consider waiting for the marketing of Shingrix. (Now available). Shingrix was just approved Oct 12/17; it is a non-live adjuvanted shingles vaccine.(2)
References: 1. NACI Herpes Zoster vaccine statement
2. https://www.gsk.com/en-gb/media/press-releases/gsk-announces-first-approval-of-shingrix-in-canada/

Oct. 13, 2017Does citalopram interact with azithromycin? details
 

Patient Age: 25
Patient Sex: M
Medical Problems: chlamydia/gonorrhea
no medical problems otherwise
Medication History: citalopram 10 mg daily
Response: While citalopram and azithromycin can both increase Qt interval (1-3), patient has no other risk factors(1) so there is no problem giving the combination.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-QA%20TORSADESdePoint.pdf
2. Lexicomp
3. Stockley's

Oct. 16, 2017Is there a maximum dose for Innohep or just 175 IU/kg? details
 

Response: Current Canadian references recommend a dose cap of 18 000 anti-Xa units for treatment dosing of tinzaparin.(1-3) This appears to be based on the fact few patients weighing >105 kg were included in the trials.(3)
Lexicomp,(4) Micromedex,(5) the American College of Chest Physicians Evidence-Based clinical Practice Guidelines (i.e: Chest guidelines),(6) and various review papers (7-13) recommend against dose capping. These recommendations are mostly based on a small pharmacokinetic study of 37 subjects (50% 100-130 kg; 50% 131-160 kg) which demonstrated no accumulation in obese patients of tinzaparin treatment doses based on total body weight.(14)
Some references recommend anti-Xa monitoring take place for patients weight >150 kg (5) or >190 kg.(11)
References: References:
1. RxTx [Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. CPS online: Heparins: Low Molecular Weight (CPhA); [updated 01 Jun 2015; cited 16 Oct 2017]. Available from: https://www.e-therapeutics.ca/
2. RxTx [Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. CPS online: Innohep; [updated 26 May 2017; cited 16 Oct 2017]. Available from: https://www.e-therapeutics.ca
3. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. Wells P, Forgie M. Venous Thromboembolism; [updated 01 Mar 2017; cited 16 Oct 2017].Available from: https://www.e-therapeutics.ca
4. Lexi-Comp Online™, Hudson, Ohio: Lexi-Comp, Inc.; 2017; cited 16 Oct 2017.
5. DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com (cited:16 Oct 2017).
6. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e24S–e43S
7. Nutescu A, Spinler SA, Wittkowsky A, et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009 Jun;43(6):1064-83. PMID 19458109
8. Easaw JC, Shea–Budgell MA, Wu CMJ, et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1: prophylaxis. Current Oncology. 2015;22(2):133-143. doi:10.3747/co.22.2586.
9. Pineo G, Hull R. Tinzaparin in the treatment of venous thromboemoblism. Expert Opin Pharmacother. 2003;4(12): 2355-2362
10. Ihaddadene R, Carrier M. The use of anticoagulants for the treatment and prevention of venous thromboembolism in obese patients: implications for safety. Expert Opin Drug Safety. 2016;15(1): 63-74
11. Phillips K, Dobesh P, Haines S. Considerations in using anticoagulant therapy in special patient populations. Am J Health-Syst Pharm. 2008;65(Suppl 7):S13-S21.
12. Thomson P, Brocklebank C, Semchuk W. Treatment Dosing of Low-Molecular-Weight Heparins and the Dose Cap Dilemma: Considerations for Patients in Canada. Can J Hosp Phar 2009; 62(5): 367-374.
13. Patel J, Roberts L, Arya R. Anticoagulating obese patients in the modern era. Br J Haematol. 2011; 155(2): 137-149.
14. Hainer JW, Barrett JS, Assaid CA, et al. Dosing in heavyweight/obese patients with the lmwh, tinzaparin: a pharmacodynamic study. Thromb Haemost. 2002;87:817–23.

Oct. 17, 2017Nursing Home patient needs all medications crushed. He is on Rifaximin 550 mg BID and the monograph says cannot be crushed. Is there a therapeutic alternative or can this drug actually be crushed or dissolved for administration. details
 

Response: The Canadian monograph says to swallow whole; there is nothing regarding any particular release mechanism; no info about any sort of coating. (1) The US monograph says nothing about swallowing whole, not crushing/splitting, etc. It specifies film coated.(3) The drug is not on the Do Not Crush list (US) (2) and there is a formula for suspension in which the tablets are crushed (US).(4) The product is manufacturered in the US and distributed to Canada(1); it is unlikely a different product is produced for Canada but will clarify with Salix. As such, if the same product is distributed to Canada as is used in the USA, there should be no problem with crushing.
The Canadian distributor (Lupin Pharma Canada) provided instructions for preparation of an oral suspension in which the tablets are crushed.(6)
References: 1. PM from DPD
2. http://www.ismp.org/tools/donotcrush.pdf
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/021361s012lbledt.pdf
4. https://www.google.ca/url?sa=t&rct=j&q=&esrc=s&source=web&cd=16&cad=rja&uact=8&ved=0ahUKEwixqYSn0vjWAhVY6WMKHXGWAb8QFghzMA8&url=https%3A%2F%2Fwww.nationwidechildrens.org%2FDocument%2FGet%2F79037&usg=AOvVaw1dVDZDBVJ-U5tDSYKpHRc1
5. http://www.nottinghamshireformulary.nhs.uk/chaptersSubDetails.asp?FormularySectionID=5&SubSectionRef=05.01.07&SubSectionID=I100
6. Phone/email communication with Roberta Zolcsak, Lupin Pharma/propharmagroup, Oct 18 2017; Roberta.Zolcsak@propharmagroup.com. Info in Jade\Drug Files\Rifaximin and Jade\Disease Files\24. General Info\Extemporanous Compounding-Oral\Rifaximin Preparation of Oral Suspension
*AHS Alt ROA

Oct. 17, 2017Desiccated thyroid tablets are shorted so will be switching everyone to levothyroxine. Is there a rough conversion as a first step? details
 

Response: As caller mentioned, this is a ballpark estimate that will need to be adjusted as per labs, but 60-65 mg desiccated thryoid ~ 100 mcg levothyroxine.(1,2)
References: 1. Lexicomp
2. Jade\Drug File\Thyroid (Desiccated) (=Erfa monograph)

Oct. 17, 2017Could you track down any literature that provides evidence on the potential for the use of low dose naltrexone (compounded) to help sleep? details
 

Response: Pubmed, Medline, Scopus, Trip database and Google Scholar were searched(Embase was not available but is unlikely to have results based on other searches). No relevant results were found. There has been a pilot study looking at effects of naltrexone on sleep parameters in healthy male volunteers with no sleep issues; in this study a dose of 50 mg was used.(1) Compared to placebo there was no difference in total sleep time or sleep latency; mean time in stage-2 sleep was 38% longer (p=0.0023), REM sleep was 47% shorter (p<0.0001) and REM latency increased 331% (p=0.0026) in the naltrexone group. Cochrane determined insufficient evidence to recommend naltrexone for obstructive sleep apnea.(2) The only trial that met criteria again used 50 mg and was a crossover study of 12 participants.
References: 1. The effect of naltrexone on sleep parameters in healthy male volunteers. Sramek J, Andry JM, Ding H, Riordan HJ, Leibowitz M, Cutler NR. J Clin Psychopharmacol. 2014 Feb;34(1):167-8. doi: 10.1097/JCP.0b013e3182a607ff. No abstract available. PMID: 24346745
2. Mason M, Welsh EJ, Smith I. Drug therapy for obstructive sleep apnoea in adults. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD003002. DOI: 10.1002/14651858.CD003002.pub3.
3. PubMed search
4. Medline
5. Scopus
6. Google scholar
*UpToDate, Embase not available

Oct. 18, 2017We have a client travelling to Papua New Guinea for possibly up to 6 months. He presented at the clinic today and unfortunately is leaving tomorrow. We have recommended doxycycline for malaria prophylaxis. We have not prescribed Primaquine for antirelapse therapy in quite a long time but would like to for this client as we believe it would be recommended. Is Primaquine still available in Regina? He is leaving tomorrow so has no time to get a G6PD test but we will recommend he get one when he returns before starting the Primaquine. According to CDC - When used for presumptive antirelapse therapy, primaquine is administered for 14 days after the traveler has left a malarious area. When chloroquine, doxycycline, or mefloquine is used for primary prophylaxis, primaquine is usually taken during the last 2 weeks of postexposure prophylaxis. Primaquine should be given concurrently with the primary prophylaxis medication. However, if that is not feasible, the primaquine course should still be administered after the primary prophylaxis medication has been completed. With this being said for this client would we recommend he start Primaquine during his last 2 weeks of doxycycline? details
 

Response: Primaquine is available to pharmacies in Regina.(1) As I’m sure you suspected I doubt m(any) will have it on hand so would need to order it in but it should arrive within 1 business day. You are correct that he would take 1 tablet (26.3 mg primaquine phosphate/15 mg primaquine base) once daily for 14 days or 0.75 mg/kg base once a week for 8 weeks if found to have mild to moderate G6PD deficiency.(2)
References: 1. PharmaClik
2. RxTx eCPS

Oct. 18, 2017Patient drinks almond milk and is trying to get calcium intake without constipation. She was told that tricalcium phosphate is a better salt to avoid constipation. Is there a product that contains this salt? details
 

Response: No tricalcium phosphate product can be found in Canada.(4,5,6) However, no information was found to suggest one calcium salt is associated with greater incidicence of constipation than another. In fact, Natural Medicines suggests that calcium-induced constipation is essentially a myth (2) and this idea has been debunked by a small recent randomly controlled trial (RCT).(9) In this RCT, healthy women (avg age 43 yr) took calcium carbonate or tricalcium phosphate delivering 250 mg elemental calcium BID x 2 weeks (2 week baseline, 2 week active, 2 week washout, 2 week other active) while documenting bowel habits.(9) There was no difference at the end of the study from baseline or between groups.
Should the patient be adamant as to avoid calcium supplements other than tricalcium phosphate, she can look at Osteoporosis Canada's calculator to find how she can achieve the recommended intake through diet. (7) Calcium -fortified almond milk is available in which each 250 ml contains 300 mg. (7,8)
References: 1. AHFS DI
2. Natural Medicines
3. examine. com
4. RxTx - CPhA Ca Salts monograph
5. CPMA - Vitamin and Mineral Products: Single Entity
6. LNPHD
7. http://www.almondbreeze.ca/products/almondmilk-original/
8. http://www.osteoporosis.ca/osteoporosis-canada-calcium-calculator/
9. Can J Diet Pract Res. 2016 Jun;77(2):103-5. Calcium Supplementation Does Not Contribute to Constipation in Healthy Women. Alyousif Z, Ford AL, Dahl WJ. PMID 26771423

Oct. 19, 2017We have a patient with an anaphylactic allergy to egg. Is it okay for her to receive Prevnar or Pneumovax? details
 

Medical Problems: Allergies: Egg, Sulfamethoxazole, Penicillin, Naproxen, Erythromycin, Amoxicillin
Response: There does not appear to be any egg protein that exists in either Pneumovax or Prevnar. Regardless, most recent recommendations by National Advisory Committee on Immunization (NACI) explains that an egg allergy is NOT a contraindication to receiving the flu vaccine, which contains egg albumin, but that additional monitoring may be required.
References: 1. https://www.canada.ca/en/public-health/services/immunization/national-advisory-committee-on-immunization-naci/canadian-immunization-guide-chapter-on-influenza-statement-on-seasonal-influenza-vaccine-2016-2017-addemdum-laiv-use-egg-allergic-individuals.html
2. http://www.immunize.org/catg.d/p2011.pdf
3. Pneumovax Monograph
4. Prevnar Monograph

Oct. 19, 2017Can 5-fluorouracil be used in the treatment of plantar warts? details
 

Response: There is some off-label evidence, but the quantity/quality of evidence is weak. Cure rates with 5% 5-FU range absolute increases of 10-30% better than placebo (2-4). The trials usually applied the 5-FU twice daily under occlusion, for 4-26 weeks, average use of 12 weeks (4). Should not be used near nails (3).
References: 1. MM
2. https://www.ncbi.nlm.nih.gov/pubmed/16703777
3. http://www.bpac.org.nz/BPJ/2014/December/plantar-warts.aspx
4. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001781.pub3/full

Oct. 24, 2017Treating croup in kids . Is there any new / updated information? Our current policy at Outpatients is 0.6 mg/kg dexamethasone. Is there a maximum tolerable dose? Lexi said 8-20 mg as one time dose. In this case, we ended up giving 15 mg. details
 

Response: All recent references suggest dexamethasone for all severities of croup(1,3,4); UpToDate and CTC suggest a lower dose of 0.15-0.3 mg/kg may be adequate for less severe cases though this is based on limited information.(2,3) All references include the dose of 0.6 mg/kg either as the dose (moderate/severe [1], severe [3], all severities [4]) or as the upper end of the range of doses. UpToDate and CTC suggest a maximum dose of 10 mg dexamethasone though neither provide rationale. (2,3) It looks like 10 mg may be a standard maximum dose in adults.(5)
References: 1. UTD - Croup: Approach to management. Algorithm: Management of croup in the outpatient and emergency department settings
2. UTD _ Croup: Pharmacologic and supportive interventions
3. RxTx - Croup
4. Oliva Ortiz-Alvarez; Canadian Paediatric Society, Acute Care Committee. Acute management of croup in the emergency department. 24 May 2017; Paediatr Child Health 22(3):166-169. https://www.cps.ca/en/documents/position/acute-management-of-croup
5. Lexicomp

Oct. 25, 2017Do you have a chart of what opioid to use if someone has an allergic reaction to one? details
 

Response: Pharmacist's letter has an opioid decision algorithm that includes intolerances to previous allergies.(1) Also, Lexicomp has some information.(2)
References: 1. PL - Analgesic options for patients with allergic-type opioid reactions. Pharmacist's Letter/Prescriber's Letter 2006;22(2):220201.
2. Lexicomp - Opioid Allergy/Hypersensitivity (Drug Allergy and Idiosyncratic Reactions)

Oct. 25, 2017Can Lamivudivine Apo 100 mg tablets besplit or crushed? details
 

Response: 3TC (lamivudine) tablets can be crushed. (3)
References: 1. http://www.ismp.org/tools/donotcrush.pdf
2. https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf
3. http://www.hivclinic.ca/main/drugs_extra_files/Crushing%20and%20Liquid%20ARV%20Formulations.pdf
*AHS ROA

Oct. 25, 2017Is it okay to give Fluzone vaccine at the same time as Zostavax? details
 

Response: Yes, this is okay as they are given on the same day and Fluzone is not live.(1)
References: 1. Cdn Immunization Guidelines - https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-1-key-immunization-information/page-10-timing-vaccine-administration.html

Oct. 25, 2017The screening form for influenza vaccine asks if the patient has had any immunizations in the past 4 weeks. An 11 year old has had 4 or 6 in the last week. Is there any reason he cannot get Fluzone today? details
 

Response: The vaccine screening form is for all vaccines, not just influenza; the question regarding history of other vaccinations in the last 4 weeks is only pertinent to live parenteral vaccines that are intended to be administered today.(1) While Flumist is a live attenuated vaccine (2), because it is not parenteral, it is not subject to this timing issue.(2) As such, the child can receive any influenza vaccine today.
References: 1. https://www.skpharmacists.ca/members/secureMedia/view/1541
2. http://medsask.usask.ca/documents/newsletters/34.8%20Influenza%20Vaccine%20Update%202017.pdf

Oct. 26, 2017Is mefloquine OK for someone with G6PD (Glucose-6-phosphate dehydrogenase) deficiency? details
 

Medical Problems: Going to Uganda
- G6PD deficiency, his records from Africa state never to take sulfa, quinine, nitrofurantoin, asa, etc.
- Unsure of what original exposure was that caused an issue
Response: Mefloquine is listed as a medication to avoid on a list of g6pd deficiency drugs to avoid list.(1)
Use of primaquine is contraindicated in the presence of G6PD deficiency due to high risk of hemolysis, which can be life threatening. Chloroquine is considered contraindicated by the manufacturer in the presence of G6PD deficiency, although significant hemolysis is unlikely at prophylactic doses. Hemolysis is not a concern for use of other antimalarials when used in prophylactic doses. (2)
References: 1. http://g6pddeficiency.org/wp/living-with-g6pd-deficiency/drugs-to-avoid-list/#.WfNRYltSyUl
2. CATMAT 2014

Oct. 27, 2017Do you have a formulation for preparing carnitine 100mg/ml solution? Is it safe to mix the powder with distilled water only? details
 

Response: Referred to commercially available product: DIN 02144336, Carnitor solution 100 mg/ml 118 ml, Leadiant Biosciences McKesson #61283.(1)
References: 1. PHarmaClik

Oct. 31, 2017I saw an article about link between statins and memory/dementia but can't find it. Do you have any information? details
 

Response: Below is information from UpToDate on the subject:
Concerns have been raised in the media and popular press about cognitive dysfunction and memory loss associated with statin use. A review of adverse events reported to the US Food and Drug Administration between November 1997 and February 2002 found 60 reports of patients who had memory loss associated with statins. Fourteen of 25 patients had improvement when the statin was discontinued, and four had recurrence of memory loss on rechallenge. The statins involved were simvastatin (36 patients), atorvastatin (23 patients), and pravastatin (1 patient).

Although this analysis of adverse event reports does not show that statins cause memory loss, the apparently high rate of reports with lipophilic statins (simvastatin and atorvastatin) compared with hydrophilic statins (pravastatin) does suggest a possible biologic effect. Randomized trials of lovastatin and simvastatin have shown some evidence of minor decrements in cognitive function as measured by neuropsychological testing. A systematic review of randomized trials and observational studies found that published data do not suggest that statins harm cognition; however, the quality of the evidence was felt to be only low to moderate, particularly with regard to high-intensity statin therapy. A 2015 systematic review of randomized trials similarly concluded that statin therapy was not associated with harming cognitive function in either cognitively normal patients or those with Alzheimer's disease. However, randomized trials can fail to detect rare medication side effects. A large database observational study found an association between first exposure to statin therapy and acute memory loss (within 30 days); however, the same association was found for other lipid lowering agents and the authors thought it more likely that the result reflected detection bias rather than a true causal effect of multiple lipid lowering therapies. In our experience, we have encountered rare patients who appear to experience cognitive side effects on a statin that resolve with discontinuation and recur with reinstitution; some of these patients appear to tolerate an alternative statin.

In the absence of more definitive data, it may be appropriate for physicians to determine whether statin therapy was recently initiated in patients who develop new memory loss. If an individual patient appears to have memory loss associated with lipophilic statin therapy (simvastatin, lovastatin, atorvastatin, or fluvastatin) and has a strong indication for lipid lowering therapy, it would be reasonable to attempt treatment with a more hydrophilic statin (pravastatin or rosuvastatin).
In contrast to the above observations suggesting that statins may produce cognitive impairment, other studies have suggested that statins may have a role in the prevention of dementia. (2)
This is information from the CPhA Statin monograph:
Case reports have suggested an association between all statins and cognitive impairment (e.g., memory loss, confusion). There has been a variable time to onset (1 day to years) and symptoms have generally resolved within a median of 3 weeks after statin discontinuation. A systematic review and meta-analysis of high-quality trials was unable to show that statins alter cognition in the short term. However, there was evidence suggesting long-term statin treatment reduced the incidence of dementia. Patients should be monitored for signs of cognitive impairment and treatment modified if appropriate.(3)
References: 1. https://www.medscape.com/viewarticle/871836
2. UTD - Rosenson R. Statins: Actions, side effects, and administration. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 01 Nov 2017. Available from www.uptodate.com. Subscription and login required.
3. CPS - CPhA Statin monograph
*RxFiles

Oct. 31, 2017I looked (CPSS, Pharmacist Letter, internet general) for a tapering regimen for otrivin nasal spray for a patient who had been using it for a year. Do you have anything you could share with the doctor? I know in general it can be challenging. Topical nasal steroids or oral might be indicated. details
 

Response: The best (though still very limited) studied strategy for rhinitis medicamentosa is, as suggested, intranasal corticosteroids.1,2
In one of the small randomized trials, fluticasone propionate 50 mcg/spray - 2 sprays per nostril once daily or placebo were administered to subjects for 14 days. All of the subjects (n=20) had been using nasal decongestants at a rate of 1-15 sprays per day for a minimum 3 years continuously and as long as 15 years. Nasal tissue inflammation was measured via rhinostereometry and subjects kept a symptom diary. All scores improved statistically significantly (SS) compared to baseline in both groups. Comparing fluticasone to placebo, rhinostereometry was SS more improved at 1 week but not 2. There were no SS differences in symptom scores; however, the time for each group to achieve SS improvement in symptoms occurred at day 4 (morning and evening scores) for the fluticasone group and days 9 (morning scores) and 7 (evening scores) in the placebo group. Essentially, fluticasone hastened the time to improvement.1
Presumably, the patient would discontinue the nasal steroid after at least 14 days’ treatment. However, it is possible complete recovery may take as long as a year.3 While it has not been studied, it has been suggested that for patients in whom nasal mucosa is too inflamed to allow adequate penetration of the nasal steroid, oral prednisone for 5 days along with nasal steroid use can be considered.3,4
References: References:
1. Hallen H, Enerdal J, Graf P. Fluticasone propionate nasal spray is more effective and has a faster onset of action than placebo in treatment of rhinitis medicamentosa. Clin Exp Allergy 1997 May;27(5):552-558
2. Vaidyanathan S, Williamson P, Clearie K, et al. Fluticasone reverses oxymetazoline-induced tachyphylaxis of response and rebound congestion. Am J Respir Crit Care Med. 2010;182(1):19.
3. Lieberman P. Chronic nonallergic rhinitis. In: UpToDate, Basow, DS (Ed), Waltham MA, 2017. Cited 01 Nov 2017. Available from www.uptodate.com. Subscription and login required
4. DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 116234, Rhinitis medicamentosa; [updated 2017 Jun 06, cited 01 Nov 2017]; [about 2 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=116234 Registration and login required.

Nov. 1, 2017I am seeking assistance regarding a patient with chronic pain from cervical spinal stenosis. He was prescribed Gabapentin 600mg PO TID by his neurosurgeon, and finds the pain control well managed, but the side effects of drowsiness significant. I would like to switch him to Pregabalin and add Amitriptyline if needed to see if that helps his symptoms. What would you suggest for the switch from his high dose of Gabapentin to Pregabalin? details
 

Medical Problems: chronic pain secondary to cervical spinal stenosis
Medication History: ASA 81 mg, Atacand 8 mg, bisoprolol 2.5 mg daily, gemfibrozil 600 mg qd, rosuvastatin 10 mg OD
carbidopa/levodopa 25/100 mg 5 times daily
gabapentin 600 mg TID, acetaminophen w/codeine
atrovent inhaler QID, salbutamol inhaler, rabeprazole 20 mg OD
Response: There has been one small clinical trial that investigated switching from gabapentin to pregabalin.(2) In this trial, a patient on a daily dose of 1800 mg gabapentin was switched to pregabalin 150 mg PO BID and the switch was made abruptly (i.e. Day 0 of study taking gabapentin TID; Day 1 taking pregabalin 150 mg BID). This switch was well-tolerated both in terms of adverse effects and maintenance of pain control. They did note that those whose pain was controlled on gabapentin were more likely to respond to pregabalin and, similarly, those who experienced adverse effects to gabapentin were more likely to experience adverse effects to pregabalin.

A kinetic modelling study determined that a daily dose of 1800 mg gabapentin would be about equivalent to 300 mg pregabalin daily.(1) This modelling study also looked at concentrations of gabapentin and pregabalin using two switching strategies: abrupt switch as above and a cross-taper where the first 4 days involved 50% of the usual gabapentin dose + 50% of the target pregabalin dose. On day 5 the gabapentin would be discontinued and pregabalin increased to the target dose. Based on expected concentrations, the authors of this study concluded both methods should be tolerated equally.

Considering the abrupt switch has been studied in humans in which it was tolerated and is much easier for the patient to understand, that may be a preferred method.
References: 1. Bockbrader HN1, Budhwani MN, Wesche DL. Gabapentin to pregabalin therapy transition: a pharmacokinetic simulation. Am J Ther. 2013 Jan;20(1):32-6. PMID 23018586
2. Toth C. Substitution of gabapentin therapy with pregabalin therapy in neuropathic pain due to peripheral neuropathy. Pain Med. 2010;11(3):456-65.
3. http://www.pharmacytimes.com/contributor/jeffrey-fudin/2015/09/how-gabapentin-differs-from-pregabalin

Nov. 1, 2017QT prolongation queston - patient on hydroxychloroquin (HCQ) and doctor wants to start nortriptyline for sleep and depression. Is there a best option for an antidepressant that is the least likely to be of concern? details
 

Patient Age: 75
Patient Sex: F
Medical Problems: dx: CHF, kidney failure in one kidney
eGFR 33 ml/min
Medication History: carvedilol 3.25 mg, adalat 60 mg, coversyl 8 mg, clonazepam od, one alfa
nortriptyline 10 mg initial
hydroxchloroquine 400 mg daily
Response: This patient scores 9 using the QT tool [(age(1), gender(1), HF (though EF not known)(3), QT drug (1 - bc nortriptyline, HCQ not heavy hitters), use of >=2 QT (3) = 9] which puts her at the high end of the moderate risk of 7-10.(1) While the risk of nortripyline/HCQ is not great, the nortriptyline dose is likely to increase and/or be substituted with a different antidepressant; most antidepressants have QT prolonging effects.(2) Therefore, suggested baseline ECG and proceed according to results.(1,2)
References: 1. Jade\Dz Files\3. CV\QT Prolongation\QT Prolongation Risk Assessment Tool
2. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-QA%20TORSADESdePoint.pdf

Nov. 1, 2017I have had a few patients phoning our Women’s Mid-Life Health Program and asking if their prescription for topical testosterone is the reason they are having trouble sleeping. I have not found anything conclusive so thought I’d ask your opinion. details
 

Response: Checked several controlled trials,(1-8) a review of trials(10) and UpToDate.(9) None of these sources reported insomnia/sleep as an adverse effect of low-dose testosterone in women. This is not to say it is not possible as these are all small trials using different doses, routes, and dosage forms; however, sleep problems may be attributable to other factors in your patients.
References: 1. Effectiveness of a low dose testosterone undecanoate to improve sexual function in postmenopausal women. Tungmunsakulchai R, Chaikittisilpa S, Snabboon T, Panyakhamlerd K, Jaisamrarn U, Taechakraichana N. BMC Womens Health. 2015 Dec 2;15:113. doi: 10.1186/s12905-015-0270-6. PMID: 26631095
2. Effects of testosterone administration on cognitive function in hysterectomized women with low testosterone levels: a dose-response randomized trial. Huang G, Wharton W, Travison TG, Ho MH, Gleason C, Asthana S, Bhasin S, Basaria S. J Endocrinol Invest. 2015 Apr;38(4):455-61. doi: 10.1007/s40618-014-0213-3. Epub 2014 Nov 28. PMID: 25430996
3. Transdermal testosterone improves verbal learning and memory in postmenopausal women not on oestrogen therapy. Davis SR, Jane F, Robinson PJ, Davison SL, Worsley R, Maruff P, Bell RJ. Clin Endocrinol (Oxf). 2014 Oct;81(4):621-8. doi: 10.1111/cen.12459. Epub 2014 May 5. PMID: 24716847
4. Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency. Guerrieri GM, Martinez PE, Klug SP, Haq NA, Vanderhoof VH, Koziol DE, Popat VB, Kalantaridou SN, Calis KA, Rubinow DR, Schmidt PJ, Nelson LM. Menopause. 2014 Sep;21(9):952-61. doi: 10.1097/GME.0000000000000195. PMID: 24473536
5. Testosterone dose-response relationships in hysterectomized women with or without oophorectomy: effects on sexual function, body composition, muscle performance and physical function in a randomized trial. Huang G, Basaria S, Travison TG, Ho MH, Davda M, Mazer NA, Miciek R, Knapp PE, Zhang A, Collins L, Ursino M, Appleman E, Dzekov C, Stroh H, Ouellette M, Rundell T, Baby M, Bhatia NN, Khorram O, Friedman T, Storer TW, Bhasin S. Menopause. 2014 Jun;21(6):612-23. doi: 10.1097/GME.0000000000000093. PMID: 24281237
6. Effect of estrogen and testosterone replacement therapy on cognitive fatigue. Möller MC, Rådestad AF, von Schoultz B, Bartfai A. Gynecol Endocrinol. 2013 Feb;29(2):173-6. doi: 10.3109/09513590.2012.730568. Epub 2012 Oct 25. PMID: 23095007
7. Testosterone pellet implants and migraine headaches: a pilot study. Glaser R, Dimitrakakis C, Trimble N, Martin V. Maturitas. 2012 Apr;71(4):385-8. doi: 0.1016/j.maturitas.2012.01.006. Epub 2012 Feb 10. PMID: 22310106
8. Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen. Nachtigall L, Casson P, Lucas J, Schofield V, Melson C, Simon JA. Gynecol Endocrinol. 2011 Jan;27(1):39-48. doi: 10.3109/09513590.2010.487597. PMID: 21142609
9. UTD - Overview of androgen deficiency and therapy in women
10. Reis SLB, Abdo CHN. Benefits and risks of testosterone treatment for hypoactive sexual desire disorder in women: a critical review of studies published in the decades preceding and succeeding the advent of phosphodiesterase type 5 inhibitors. Clinics. 2014;69(4):294-303.

Nov. 1, 2017If someone is on Remicade and can't get Pneumovax, which product should they receive? details
 

Patient Age: 25
Patient Sex: M
Medication History: Remicade
Response: It is unclear if a patient on Remicade would be considered immunocompromised; the Canadian Immunization guidelines include use of long-term corticosteroids, chemotherapy, radiation therapy, and post-organ transplant therapy (2) whereas the CDC Guidelines consider iatrogenic immunosuppression (diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids and radiation therapy)(3) suggesting a person on Remicade would meet the criteria.
If it's decided to give pneumococcal, he should receive: 1x Pneu-C-13 followed at least 8 weeks later by 1x Pneu-P-23 followed at least 5 years later by Pneu-P23.(1,2)
References: 1. http://medsask.usask.ca/documents/hot-topics/Pneumococcal_vaccinations.pdf
2. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-16-pneumococcal-vaccine.html#risk-factors
3. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html

Nov. 6, 2017Pediatric 16 year old with tuberculosis (TB) on isonizazid, pyrazinamide, rifampin, ethambutol started 3 days ago. She also has H.pylori and is starting treating with amoxicillin, clarithromycin, pantoprazole. Drug interaction between clarithromycin and rifampin - increased clarithromycin; rifampin decreases clarithromycin concentration. 1. Would there be an alternative regimen that would be preferred? 2. Is this interaction significant enough to need switching? details
 

Patient Age: 16
Patient Sex: F
Medical Problems: H.Pylori - MDs want to treat
TB
Medication History: rifampin, isoniazid, ethambutol, pyrazinamide
morphine, ibuprofen, ondansetron (PRN)
Response: There is a significant interaction between rifampin and clarithromycin; rifampin may reduce clarithromycin levels up to 90%(1) and therefore this combination cannot be considered.
In terms of treatment of H Pylori in children, research is limited. The most recent guidelines are from 2011 and do suggest to consider resistance patterns and modify as needed. (7) Triple therapy is no longer recommended as first line in adults due to resistance. (2,4) A quadruple therapy that has been studied in children:
PPI + metronidazole 20 mg/kg/d DIV BID + amoxicillin 50 mg/kg/d DIV BID + bismuth 8 mg/kg/d DIV BID x 10-14 d.(7) Lexicomp flags an interaction between pantoprazole and rifampin(8); however, this would just promote formation of the active pantoprazole metabolite.
Alternatives:
PPI + Amoxicillin + Levofloxacin 250 mg BID or 500 mg OD x 14d (7). Caller states levofloxacin is only permitted for treatement of TB in the health region.
PPI + Amoxicillin + rifabutin (4) This is only being considered because of the current TB treatment such that the rifampin would be substituted with rifabutin for 14 days; however, rifabutin is much more expensive and this alternative is not likely viable.
References: 1. Stockley's
2. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-Hpylori.pdf
3. MUMS app
4. Bugs and Drugs app
5. Cdn TB Standards
6. http://www.topalbertadoctors.org/download/362/h_pylori_guideline.pdf?_20170531132925
7. Jade\Dz Files\1. Infectious Dz\H Pylori\ESPGHAN and NASPGHAN guidelines, 2011
8. Lexicomp
9. Stockley's
10. eCPS TCN CPhA monograph
11. Dynamed Plus
12. drugs.com
13. DrugDex
14. UTD - Clinical manifestations, diagnosis, and treatment of brucellosis

Nov. 6, 2017I need to give azithromycin and ceftriaxone to client on Tivicay and Truvada. Are there any interactions? details
 

Response: No known interactions.(2,3)
References: 1. http://www.catie.ca/en/practical-guides/hiv-drug-treatment/appendices/b
2. Stockley's
3. Lexicomp

Nov. 6, 2017I have a male patient with a urinary tract infection (UTI) resistant to smx/tmp (Septra) and cephalosporin and sensitive to ampicillin, ciprofloxacin and nitrofurantoin. He is on sotalol so ciprofloxacin is not an option. I have always heard nitrofurantoin is not an option in men because adequate tissue concentrations are not reached. Is this true? details
 

Patient Age: 73
Patient Sex: M
Medical Problems: UTI - lower tract
Medication History: sotalol
Response: Nitrofurantoin does not achieve adequate renal tissue concentrations and males are typically considered complicated as functional or anatomical abnormalities are often present.(2) As such, nitrofurantoin is not considered a treatment option.(2) According to the patient's C&S results, amoxicillin-clavulanate 875 mg PO BID x 10d is an appropriate option.(2)
References: 1. eCPS - Nitrofurantoin CPhA monograph
2. Bugs and Drugs

Nov. 7, 2017Can we give influenza vaccine to patients who are on immunosuppressants for organ transplant? details
 

Response: A question on the screening document does ask about the presence of immunosuppressive drugs or conditions that could be interpreted as these patients should not be vaccinated.(4) However, the guide that accompanies the screening tool states this is not a concern for the inactivated influenza vaccine, but may be an issue with other vaccines.(5) Immunocompromised patients are especially vulnerable to influenza and are encouraged to be vaccinated in the pharmacy influenza vaccination program.(1,3)
References: 1. http://formulary.drugplan.ehealthsask.ca/PDFs/2017-18InfluenzaHandbookforSaskatchewanPharmacists.pdf
2. http://formulary.drugplan.ehealthsask.ca/PDFs/650%202017-18%20Influenza%20Immunization%20Program%20October%2016%202017.pdf
3. https://www.skpharmacists.ca/uploads/media/59ea766e58fb2/media-kit-faqs-2017-2018-flu-season.pdf?token=[M1598]
4. https://www.skpharmacists.ca/members/secureMedia/view/1432
5. https://www.skpharmacists.ca/members/secureMedia/view/1541

Nov. 7, 2017Proctofoam HC is shorted by manufacturer - what can be recommended instead? details
 

Response: No other foams are available so suppositories or ointments will be the option if hydrocortisone and pramoxine are still desired; choice will depend on patient preference. Anugesic-HC, Proctodan-HC contain HC and pramoxine.(1)
References: 1. http://medsask.usask.ca/professional/guidelines/hemorrhoids.php

Nov. 17, 2017EENT prescribed Nasonex for eustacean tube dysfunction. Patient has fluid in ears/infection. Is Nasonex appropriate? details
 

Patient Age: 40
Patient Sex: M
Medication History: furosemide
Response: The treatment of dilatory eustachean tube dysfunction is aimed at the underlying etiology, of which include rhinosinusitis and rhinitis, such that nasal steroids are appropriate treatment if these etiologies exist.(1)
References: 1. UTD - Eustachian tube dysfunction

Nov. 17, 2017Is there any evidence to support using IV beta-lactams (ie: piperacillin/tazobactam) in place of oral amoxicillin in treatment of H.pylori in patients who have another indication to be on IV treatment? In all cases we have seen recently, the patient has had another indication for IV pip/tazo and required treatment of H.pylori and was otherwise able to take the rest of treatment orally. Question came up of whether the IV pip/tazo would be sufficient or whether amoxicillin should still be used? details
 

Response: On paper, it seems that pip-tazo should be effective for H. pylori treatment:
- Pip-taz has a similar spectrum to amoxicillin that includes many gram negative and gram positive bacteri(1) H. pylori is a gram-negative bacillu(2,3)
- Pip-taz distributes to the intestinal mucos (1)
- In vitro susceptibility of H. Pylori to pip-taz, similar to that of amoxicillin, has been demonstrate (4-6) though demonstrated only bacteriostatic effects in one of these.(4)
However, I only found one in vivo case of pip-taz treatment for H. pylori (organism was unknown at time of treatment) and this was a case of bacteremia.(2) The challenge with H.pylori treatment is not antibiotic sensitivity (at least initially), but delivery to the required site – within and below the layer of mucus adherent to the gastric epithelial cells.(7,8) As mentioned above, pip-taz reportedly distributes to the intestinal mucosa, which is promising, but not definitive.
I completely understand the absurdity that adding amoxicillin to pip-taz presents. Based on the information above I am not confident pip-taz will eradicate H. pylori; however, you and your team may come to a different conclusion.
References
1. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 21 Nov 2017.
2. Han XY, Tarrand JJ, Dickey BF, et al. Helicobacter pylori bacteremia with sepsis syndrome. J Clin Microbiol. 2010 Dec;48(12):4661-3.
3. Gerrits MM, Schuijffel D, van Zwet AA, et al. Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother. 2002 Jul;46(7):2229-33.
4. Hassan IJ, Stark RM, Greenman J, et al. Activities of beta-lactams and macrolides against Helicobacter pylori. Antimicrob Agents Chemother. 1999 Jun;43(6):1387-92.
5. Oyedeji KS, Smith SI, Coker AO, et al. Antibiotic susceptibility patterns in Helicobacter pylori strains from patients with upper gastrointestinal pathology in western Nigeria. Br J Biomed Sci. 2009;66(1):10-3.
6.Dore MP, Graham DY, Sepulveda AR, et al. Sensitivity of amoxicillin-resistant Helicobacter pylori to other penicillins. Antimicrob Agents Chemother. 1999 Jul;43(7):1803-4.
7. Atherton JC, Blaser MJ. Helicobacter pylori Infections. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130§ionid=79736176. Accessed 21 Nov 2017.
8. Butzler J, Przondo-Mordarska A. Prevalence of antibiotic resistance in Helicobacter pylori strains in Poland. Clin Microbiol Infect 1998; 4(12): 726-28
References: eferences
1. AHFS® Drug Information. Lexi-Comp Online, Bethesda, MD: American Society of Health-System Pharmacists; 2017; accessed 21 Nov 2017.
2. Han XY, Tarrand JJ, Dickey BF, et al. Helicobacter pylori bacteremia with sepsis syndrome. J Clin Microbiol. 2010 Dec;48(12):4661-3.
3. Gerrits MM, Schuijffel D, van Zwet AA, et al. Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother. 2002 Jul;46(7):2229-33.
4. Hassan IJ, Stark RM, Greenman J, et al. Activities of beta-lactams and macrolides against Helicobacter pylori. Antimicrob Agents Chemother. 1999 Jun;43(6):1387-92.
5. Oyedeji KS, Smith SI, Coker AO, et al. Antibiotic susceptibility patterns in Helicobacter pylori strains from patients with upper gastrointestinal pathology in western Nigeria. Br J Biomed Sci. 2009;66(1):10-3.
6.Dore MP, Graham DY, Sepulveda AR, et al. Sensitivity of amoxicillin-resistant Helicobacter pylori to other penicillins. Antimicrob Agents Chemother. 1999 Jul;43(7):1803-4.
7. Atherton JC, Blaser MJ. Helicobacter pylori Infections. In: Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e New York, NY: McGraw-Hill; 2014. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1130§ionid=79736176. Accessed 21 Nov 2017.
8. Butzler J, Przondo-Mordarska A. Prevalence of antibiotic resistance in Helicobacter pylori strains in Poland. Clin Microbiol Infect 1998; 4(12): 726-28

Nov. 18, 2017Our patient going to be starting acetylcysteine 600 mg and has an ASA allergy. Is there any cross-reactivity? details
 

Response: No cross-reactivity has been reported to acetylcysteine. (1)
References: 1. Lexicomp - Acetylcysteine Allergy (Drug Allergy and Idiosyncratic Reactions)

Nov. 20, 2017I had a request to try to find a lactose free BCP tablet. The reason is that the person is Vegan and feels that lactose is a milk product. Where do drug companies get lactose from? Is it extracted from milk or synthesized? Any ideas on what she could take. I suggested a patch or IUD, but she is hoping to find a pill. details
 

Response: All of the currently marketed oral contraceptives contain lactose in the active tablets. (1,2) Commercial lactose is derived from cows' milk.(3)
References: 1. PM from eCPS
2. PM from DPD
3. 2017 Handbook of Pharmaceutical Excipients

Nov. 22, 2017Nurse practitioner had a patient request tretinoin microsphere gel. Is it any better than the original gel? details
 

Response: The formulation of Retin-A micro makes the product better tolerated compared to the same concentration of the cream.(2,3,5) As such, patients may be able to tolerate a greater concentration than with the original tretinoin products. If potency cannot be increased due to irritation, Retin-A Micro may be of benefit; however if irritation is not a problem and the tretinoins are simply not effective (despite increasing potency), the microsphere formulation will not be any more beneficial.
References: 1. CTC Acne
2. eCPS
3. PL Detail-Document, Pharmacotherapy of Acne. Pharmacist’s Letter/Prescriber’s Letter. February 2016.
4. http://medsask.usask.ca/professional/guidelines/acne-mild.php
5. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-acne.pdf

Nov. 22, 2017Is there gluten in PMS hydromorphone 1 mg (DIN 00885444); apo-naproxen 500 mg? details
 

Response: Neither of these products contain ingredients that are sources of gluten.(1-3) All manufacturers will provide the caveat that they do not screen raw materials for trace amounts.(3)
References: 1. PM from DPD
2. Jade/Dz Files/24. General Files/Excipients/Gluten Cheat Sheet
3. http://www.apotex.com/ca/en/products/allergen.asp

Nov. 22, 2017When switching from NovoRapid to Humalog, do you convert unit-to-unit? details
 

Response: When converting from regular to rapid-acting insulin, the conversion is unit-per-unit(1) so by extension, converting from one rapid-acting to another rapid acting is also unit-per unit. Of course adjustment may be required so should be monitored closely at the beginning.
References: 1. Canadian Pharmacist's Letter 2015; 31(11):311128

Nov. 22, 2017If you've had the Zostavax, can you also get the Shingrix vaccination? When is Shingrix going to be available. details
 

Response: Preliminary data suggests it is safe to administer Shingrix five or more years after Zostavax vaccination.(1) The company is now telling us that the Canadian release date will be in early January 2018. (2)
References: 1. Shingrix Hot Topic - medSask.usask.ca
2. GSK Customer Service - 1-800-387-7374

Nov. 22, 2017How much epinephrine is in epinephrine bitartrate powder? details
 

Response: The molecular formula and weight of epinephrine is C9H13NO3,C4H6O6 333.3 (C4H5O6 represents the bitartrate)and that of epinephrine is C9H13NO3 183.2 such that 1 g epinephrine bitartrate powder would contain 550 mg epinephrine.(1)
References: 1. Martindale
2. https://comptox.epa.gov/dashboard/dsstoxdb/results?utf8=%E2%9C%93&search=epinephrine, https://comptox.epa.gov/dashboard/dsstoxdb/results?search=DTXSID3049415
3. https://pubchem.ncbi.nlm.nih.gov/compound/5815#section=Top

Nov. 22, 2017Patient who has possible osteomyelitis was cultured with pseudomonas sensitive to ceftazidime. Are there any oral cephalosporins that could be used? When questioned rationale of PO for osteomyelitis, caller said patient is reluctant to have IV antibiotics. details
 

Response: If the infection is osteomyelitis, IV treatment is required.(1,3,4) None of the oral cephalosporins have activity against pseudomonas (1) and the only oral antibiotic that would have activity is ciprofloxacin (if it is sensitive)(4), but again, osteomyelitis requires IV therapy.
References: 1. Bugs and Drugs app
2. http://www.globalrph.com/bugs2.cgi
3. Jade\Dz Files\1. Infectious Dz\GeneralAntimicrobial Treatment Guidelines for Common Infections_jun 2016
4. CTC - Acute osteomyelitis.

Nov. 22, 2017Trying to find out if premarin oral tablets can be inserted intravaginally, as the manufacture is currently not supplying premarin vaginal cream...The patient is using it for vaginal symptoms of menopause. details
 

Response: I didn’t find any information about vaginal administration of Premarin tablets. While I don’t have safety concerns per se, my initial concerns are that depending how the tablet disintegrates, it may be irritating and it is possible it won’t disintegrate properly to be effective. These are simply theoretical concerns; however, I do feel it is preferable to use another product that is manufactured for vaginal use such as Vagifem 10 mcg tablets or Estring 2 mg. These products are both on the SK and NIHB formularies. If the patient is a SK health patient, I do understand they are more expensive than the Premarin cream which may be a barrier.(1,2)
While I do still recommend the above products, in my research I did come across a very small study in which vaginal Premarin cream was compared to vaginal administration of an oral contraceptive tablet (containing 30 mcg ethinyl estradiol/250 mcg levonorgestrel) in Thai women.(5) Estrogen levels were not measured (not possible because of the types of estrogen used). There were no differences observed in terms of vaginal pH (it dropped in both groups) and both groups experienced marked improvement in urogenital symptoms including vaginal dryness, dyspareunia, urinary frequency, and urinary urgency. The researchers concluded, vaginal administration of the oral contraceptive tablet is a reasonable option and is much less expensive than Premarin vaginal cream. A couple of notes:
- We don’t have a product with 250 mcg levonorgeseltr(6), but it is the ethinyl estradiol component that is important.
- The patients in this study were only followed for 8 weeks so long term safety /efficacy is not known
- The oral contraceptive was administered once weekly
References: 1. PharmaClik
2. Online Formulary
3. CTC - Menopause
4. Medline: Vaginal administration of estradiol: effects of dose, preparation and timing on plasma estradiol levels. [Review] Santen RJ. Climacteric. 18(2):121-34, 2015 Apr.
5. Medline: The use of two estrogen preparations (a combined contraceptive pill versus conjugated estrogen cream) intravaginally to treat urogenital symptoms in postmenopausal Thai women: a comparative study. Chompootaweep S; Nunthapisud P; Trivijitsilp P; Sentrakul P; Dusitsin N. Clinical Pharmacology & Therapeutics. 64(2):204-10, 1998 Aug.
6. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-OCs-Color.pdf

Nov. 22, 2017Client born in 1981 on Copoxane supposed to have measles mumps rubella vaccine. We have Copaxone listed as an immunosuppressant but the vaccine has been recommended by her MS nurse. Should I give it to her? details
 

Response: Granted I found no direct evidence of the safety of glatiramer with live vaccines or direct evidence of impact on the immune system, however, all resources consulted consider live vaccines safe in MS patients taking glatiramer.(2,3,5,6)
References: 1. eCPS
2. Jade\Dz Files\11. Neurologic \MS\Immunization in patients with MS (Cahill et al, 2010)
3. CTC - MS
4. https://mssociety.ca/research-news/article/vaccinations-and-ms
5. Oreja-Guevara C, Wiendl H, Kieseier BC, Airas L, for the NeuroNet Study Group. Specific aspects of modern life for people with multiple sclerosis: considerations for the practitioner. Ther Adv Neurol Dis. 2014;7(2):137-149. doi:10.1177/1756285613501575. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932767/#!po=75.0000
6. Goldman M., Cohen J., Fox R., Bethoux F. (2006) Multiple sclerosis: treating symptoms, and other general medical issues. Cleve Clin J Med 73: 177–186 [

Nov. 23, 2017A patient is post-MI due to pneumosepsis. MI occurred secondary to sepsis. No stenting, valve, PCI, etc. was done--medically managed MI. Is dual-antiplatelet therapy (DAPT) needed, and for how long if at all? details
 

Patient Age: 85
Patient Sex: F
Medical Problems: ICU with pneumosepsis
MI occurred secondary to sepsis
44kg
Triponon over 1000
BMP over 3000
Post-MI medically managed, no PCI
Medication History: type 2 MI
Response: Pneumonia is the major cause of sepsis.
1. Although DAPT in medically managed patients with Acute Coronary Syndrome (ACS) is a poorly studied sub-group (1), it is still recognized that current evidence favours treatment with DAPT over nothing at all (2-5). UK guidelines (2) suggest a bare minimum of one month DAPT, ASA indefinitely, but preferably 12 months; US (3) suggests 12 months, unless treated with fibrinolytic therapy, then a minimum DAPT of 14 days (but still preferably 12 months); Canada (4) suggests 12 months DAPT; and European (5) suggests 12 months, unless high bleed risk, then 1 month is acceptable. Additionally, all guidelines recommend ticagrelor instead of clopidogrel due to higher efficacy in this population, unless the patient has a high bleed risk, then stick with clopidogrel.
References: 1. http://heart.bmj.com/content/103/8/573--- 2017 lit review
2. http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20070606094052295600
3. ACC/AHA guidelines, 2016, http://www.scai.org/Assets/20b5a0bd-f338-4abe-82ec-5076f05f405f/635948591187300000/03513-pdf
4. Canadian guidelines, https://www.ccs.ca/images/Guidelines/PocketGuides_EN/Pocket_Guides/APT_Pocket_Guide_English.pdf
5. https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/2017-focused-update-on-dual-antiplatelet-therapy-dapt

Nov. 27, 2017Are there interactions between methotrexate (MTX) and fluoxetine, celecoxib, ranitidine and colchicine? details
 

Medication History: fluoxetine, celecoxib, ranitidine, colchicine
Response: The only interaction of concern is MTX and celecoxib.(1) Theoretical concern with increased MTX levels when MTX combined with NSAIDs but less likelihood of significant interaction with lower doses of MTX (e.g. weekly doses for psoriasis treatment) and with Cox-2 specific inhibitors.(2) Celecoxib does not appear to have a significant effect on the pharmacokinetics of methotrexate according to the manufacture's monograph. (3) Coadministration of methotrexate with other agents known to induce hepatotoxicity may potentiate the risk of liver injury (rare adverse effects of NSAIDs). Methotrexate, especially at higher doses or with prolonged treatment, has been associated with hepatotoxicity including acute hepatitis, chronic fibrosis, necrosis, cirrhosis, and liver enzyme elevations.(3)

When I called MD back, she had found out the patient was only on fluoxetine, ranitidine and clonazepam. There are no reports or concerns with interactions between these drugs and MTX.(1)
References: 1. Lexi Interactions
2. RxTx - celecoxib monograph
3. Drugs.com Interaction Checker

Nov. 27, 2017Is doxycycline contraindicated in a patient with elevated Liver Function Tests? details
 

Patient Age: 33
Patient Sex: M
Medical Problems: acne
Response: Doxycycline is cleared primarily by the kidneys so is unaffected by liver function impairment unless severe.(1) Rare cases of hepatic toxicity have been reported with long-term use of doses larger than recommended in patients with renal insufficiency or concomitant administration of other potenitally hepatotoxic drugs.(2)

Nov. 28, 2017We are reviewing our insulin strategies in RQHR, including determining if a product needs to be wardstock or can be dispensed patient-specific. For insulin regular (ie. Humulin R), nurses on a medicine ward are suggesting this product needs to be wardstock for treatment of hyperkalemia (in addition to dextrose). This product will be wardstock in critical care and emergency areas. Question: Is there any information or evidence regarding 1) the time of onset for insulin regular in hyperkalemia, and 2) if insulin regular is to be wardstock/routinely available for emergent purposes on a medicine ward or if it can be dispensed patient-specific? details
 

Response: The onset of insulin in reducing potassium levels is ~ 10-20 minutes and peaks at ~30 minutes.(2) By 60 minutes, one can expect a potassium reduction of 1-1.5 mmol/L(1)

ISMP Canada reported a case in which a patient developed anoxic brain injury presumably due to insulin administered SC for the purpose of reducing potassium levels (and, as usual, several other potential variables). One of the recommendations is that hospitals remove insulin from ward stock.(6)
References: 1. CTC - Potassium disturbances
2. UTD - Treatment and prevention of hyperkalemia in adults
3. Olson KR. Chapter 1. Emergency Evaluation and Treatment. In: Olson KR. eds. Poisoning & Drug Overdose, 6e New York, NY: McGraw-Hill; 2012. http://accessmedicine.mhmedical.com/content.aspx?bookid=391§ionid=42069814. Accessed November 29, 2017.
4. Latcha S. Electrolyte Disorders in Critically Ill Patients. In: Oropello JM, Pastores SM, Kvetan V. eds. Critical Care New York, NY: McGraw-Hill; . http://accessmedicine.mhmedical.com/content.aspx?bookid=1944§ionid=143517373. Accessed November 30, 2017.
5. Muldrew KM, Neill KK, Warmack T. Electrolyte Disorders. In: Sutton S. eds. McGraw-Hill's NAPLEX® Review Guide, 2e New York, NY: McGraw-Hill; . http://accesspharmacy.mhmedical.com/content.aspx?bookid=1432§ionid=86379272. Accessed November 30, 2017.
6. Electrolyte Homeostasis. In: Wells BG, DiPiro JT, Schwinghammer TL, DiPiro CV. eds. Pharmacotherapy Quick Guide New York, NY: McGraw-Hill; . http://accesspharmacy.mhmedical.com/content.aspx?bookid=2177§ionid=165474611. Accessed November 30, 2017.

Nov. 29, 2017I have been trying to find information on the vulvar cream –Neogyn. Unfortunately the official website has little to no information. In particular I was hoping to find out the ingredient list and where the product is being carried, as well as studies with the product efficiency. details
 

Response: Neogyn’s active ingredient is cutaneous lysate, described as cellular lysate of cultured human fetal fibroblasts, which purportedly contain a mixture of cytokines, interleukins and interferons to promote collagen formation.

I found 2 RCTs. The first was conducted in women with vulvar lichen sclerosus.(4) While the women in the control group experienced a statistically significant improvement over 12 weeks, so did the placebo group and there was no statistically significant difference between the two groups.

The second RCT was a crossover trial in women with provoked localized vulvodynia.(5) After 12 weeks there was a statistically significant reduction in pain during sexual activity and erythema that was not observed in the placebo group.

The product is not licensed in Canada so cannot be procured by any legal route so I didn’t find it anywhere you wouldn’t have. It is listed on Amazon. It appears to be available through ebay.ca for $25 + $18 shipping for 30 ml. (6)
References: 1. https://www.amazon.com/Neogyn-Vulvar-Soothing-Cream/dp/B006P2OGH0#Ask
2. http://www.businesswire.com/news/home/20140428005065/en/Switzerland%E2%80%99s-Neogyn-Feminine-Soothing-Cream-Improve-Quality
3. https://www.slideshare.net/Neogyn/goldstein-issvd-2011
4. Goldstein AT, Burrows LJ, Belkin ZR, et al. Safety and efficacy of human fibroblast lysate cream for vulvar lichen sclerosus: a randomized placebo-controlled trial. Acta Derm Venereol. 2015 Sep;95(7):847-9. doi: 10.2340/00015555-2052. PMID 25634582
5. Donders GG, Bellen G. Cream with cutaneous fibroblast lysate for the treatment of provoked vestibulodynia: a double-blind randomized placebo-controlled crossover study. J Low Genit Tract Dis 2012; 16: 427–436. PMID 22968058
6. http://n.stuccu.ca/s/Neogyn+Vulvar+Soothing
*RxTx, LNHPD, DPD, Lexicomp, LNHPD

Nov. 29, 2017Are the zoledronic acid (Aclasta) generics covered under EDS? details
 

Response: No.(1) The generic manufacturers were not compliant with generic pricing guidelines.(2)
References: 1. http://formulary.drugplan.ehealthsask.ca/
2. Communication with Donna Herbert, Pharmacist, DPEBB, Nov 30, 2017

Nov. 29, 2017One of my patients has renal dysfunction - CrCl 9 ml/min (24h). He is on metformin 1000 mg/day. I see it is controversial to use in low renal function. What would be the recommendation for his renal function? Is there a way to monitor if things are currently otherwise well? details
 

Patient Age: 49
Patient Sex: M
Medical Problems: strokes
DM
CKD - GRF = 9 ml/min based on 24h urine collection
Medication History: NPH
metformin
Response: Indeed, this is a matter of debate(1-3) and one report evaluating metformin-associated lactic acidosis in 14 patients found other causes of lactic acidosis (including clinical shock or tissue hypoxia) were noted and seemed to be the driving cause, not specifically metformin.(2) Based on a very small phase 1 trial(1), the following could be recommended:
- consider discontinuing if patient >160 kg, has unstable ischemic heart disease, severe COPD, unstable CHF or significant liver disease as these are risk factors for metabolic acidosis and we don't have data in these patients.
- calculate eGFR (ml/min/1.73 m2) using MDRD; it is quite possible this patient would technically be staged 'better' than Stage 5 renal disease
- measure fasting venous lactate, bicarbonate, pH to determine presence (or impending presence) of metabolic acidosis.
- if no metabolic acidosis, continue with metformin while regularly monitoring renal function. Consider measuring fasting venous lactate, bicarbonate and pH if change in renal function or at regular intervals (monthly?)
As this is quite onerous, one may want to switch to insulin only.
References: 1. Dissanayake A, Wheldon M, Ahmed J, et al. Extending Metformin Use in Diabetic Kidney Disease: A Pharmacokinetic Study in Stage 4 Diabetic Nephropathy. Kid Int Rep 2017;2(4):705-7012 http://www.sciencedirect.com/science/article/pii/S2468024917300591
2. https://clindiabetesendo.biomedcentral.com/articles/10.1186/s40842-015-0001-9
3. RxFiles - http://www.rxfiles.ca/rxfiles/uploads/documents/Diabetes-Metformin-LacticAcidosis-QandA.pdf
4. http://www.globalrph.com/multiple_crcl.cgi

Nov. 29, 2017What is the best way to get a patient off Estradot 25 mcg /progesterone. She already is extending the interval between patches and is experiencing hot flashes. Clonidine is ineffective. She can't take oral estrogen. What about maca? I have recommended in the past and the patient found it effective. I know we could use venlafaxine but I think that's hard to discontinue. What about low dose Birth Control? I know she has used it in the past but she didn't say how she tolerated it. details
 

Response: Estrogen is going to be the most effective agent to relieve vasomotor symptoms(3,4); however, several months are needed to taper off,(1,2) which the patient doesn't seem willing to do.
Estrogen therapies:
The patient could consider cutting the patches. This is not recommended by the manufacturer and the dose will not be exact, but it will be a way to reduce the dose without increasing the interval. Estradot is a matrix patch.(5) Other estrogen forms that may be more conducive to tapering are Divigel in which she could use smaller and smaller amounts; however, obviously this will not be accurate dosing but it is packaged in packets. Compounded topical estrogen could also be considered as she would be able to control the amount applied a little more easily and the concentration could be reduced with successive fills. This is likely to be expensive. As for using a low dose estrogen, even the lowest dose (10 mcg ethinyl estradiol) is twice as potent as what is required and what she is taking now.(4)
Non-hormonal therapies:
A non-hormonal product that may be effective for hot flashes that hasn't been tried is gabapentin.(4) She could also try antidepressants - venlafaxine or SSRIs; these will have to be tapered at discontinuation but presumably there won't be a need to rush it. In terms of natural products, maca has been studied in one trial and it had modest effects on mood, anxiety and somatic symptoms; either vasomotor symptoms - this patient's chief complaint - weren't abated or not studied.(3) Likely the most effective natural product would be soy, though increasing dietary soy intake as opposed to taking soy supplements is recommended as soy supplements may have estrogenic effects. (3)
Non-pharmacological
Smoking and obesity are associated with more severe vasomotor symptoms.(3,4) If she is a smoker and/or obese, she can try to quit and/or lose weight, which of course won't be a quick option either.
References: 1. PL Detail-Document, Hormonal Contraception in Older Women. Pharmacist’s Letter/Prescriber’s Letter. January 2016.
2. PL -Aug 2017 - Suggest a Hormone Therapy Form Based on Preference, Cost, and Convenience
3. Natural Medicines
4. CTC - Menopause
5. PL - Clinical Resource, Characteristics of Transdermal Patches. Pharmacist’s Letter/Prescriber’s Letter. July 2017.
6. eCPS

Nov. 30, 2017What is the preferred steroid eye drop in the first trimester of pregnancy. Ophthalmologist has a pregnant patient (1st trimester) with an epi scleritis. He describes it as a mild case of inflammation of the sclera and wants to know the safety/preference for product. He mentioned he would want to use a mild topical steroid such as Lotamax or Alrex (spelling). details
 

Patient Sex: F
Response: There are no human systematic studies available on the use of the newer ophthalmic corticosteroids in pregnancy. Animal data suggest low risk. Human systemic absorption is very low, suggesting that the embryo–fetal exposure, if any, would be clinically insignificant. Alrex (loteprednol 0.2%) would be a good choice for use in the first trimester since it is a low dose of a less potent corticosteroid, but really, any corticosteroid drops would be suitable for short-term use. (1,2)
References: 1. Schaefer C, Peters P, Miller RK, editors. Drugs during pregnancy and lactation: Treatment options and risk assessment. 3rd ed. San Francisco, CA: Academic Press; 2015.
2. Lexi-Comp OnlineTM , Loteprednol Ophthalmic (Briggs Drugs in Pregnancy and Lactation) , Hudson, Ohio: Lexi-Comp, Inc.; 2017; November 30, 2017.

Dec. 1, 2017Can you please do a search to confirm whether cannabis oil is dialyzable? We have a client in our hemodialysis unit who is questioning whether it’s worth it for her to take her supplement on the days when she is booked to come for dialysis. Will it be removed during the treatment? details
 

Response: This was mostly confirmed in my research. To be clear, I only found data for THC. The applicable physiochemical properties of THC are high protein binding (97%) and practically insoluble in water ( 2.8 mg/L).(1) The Dialysis Drug Handbook categorizes THC as “no published data exist but physicochemical characteristics of the drug suggest that significant drug removal is unlikely during dialysis” for conventional hemodialysis and no data for high permeability hemodialysis.(2) This reference defines conventional hemodialysis as “the use of a dialysis membrane whose in vitro coefficient of ultrafiltration (KUf) ≤8 mL/hour/mm Hg. High permeability hemodialysis is defined as the use of a dialysis membrane whose KUf >8 mL/hour/mm Hg.”(2)
I did find a case report in which a patient with heavy cannabis use (15-20 smoked cannabis cigarettes per day) complained of withdrawal symptoms following hemodialysis; the symptoms were relieved upon consumption of smoked cannabis.(3) Furthermore, the authors measured THC, an active metabolite (hydroxy-THC) and an inactive metabolite (nor-9-carboxy-THC). The levels declined sooner in this patient during hemodialysis than has been previously described. Unfortunately, the type of hemodialysis was not provided.

I suspect the findings in the case report can be attributed in part to the heavy use of cannabis. Normally I wouldn’t expect much effect of conventional hemodialysis on the clearance of THC. However, is it possible for your patient to take her cannabis oil following the HD session on those days?
References: 1. Laprevote V, Gambier N, Cridlig J, et al. Early withdrawal effects in a heavy cannabis smoker during hemodialysis. Biol Psychiatry. 2015 Mar 1;77(5):e25-6.
2. Bailie G, Mason N. 2013 Dialysis of drugs. Renal Pharmacy Consultants: Saline, MI.
3. Garrett ER, Hunt CA. Physiochemical properties, solubility, and protein binding of delta9-tetrahydrocannabinol. J Pharm Sci. 1974 Jul;63(7):1056-64.

Dec. 4, 2017Can 2 Twinrix Junior be substituted for Twinrix? details
 

Response: Yes, two Twinrix Junior are equivalent to one regular Twinrix injection.(1)
References: 1. RxTx - Twinrix monograph

Dec. 5, 2017Patient is on venlafaxine 225 mg and MD wants to add bupropion. I'm concerned because of the interaction of bupropion increasing venlafaxine levels since she is already on maximum doses. Is there a better agent that could be added? details
 

Patient Age: 61
Patient Sex: F
Medical Problems: depression
Medication History: venlafaxine 150 mg
ramipril, HCTZ, omeprazole, cetirizine, atenolol
Response: While bupropion increases venlafaxine levels, the levels of the active metabolite (approximately equipotent to venlafaxine) are reduced by nearly the same degree such that this is not a clinically significant interaction.(6) Other options include adding liothyronine or quetiapine [after assessing for QT risk].(1,4,5)
References: 1. Clin Handbook of Psychotroipc Drugs
2. UTD - Unipolar major depression in adults: Augmentation of antidepressants with stimulants and stimulant-like drugs
3. Lexicomp
4. UTD - Unipolar depression in adults: Treatment of resistant depression
5. UTD - Unipolar depression in adults: Augmentation of antidepressants with thyroid hormone
6. Stockley's

Dec. 5, 2017Twinrix was written for a family going to Mexico. The parents (in their 30s) received full Hep B series in elementary school. The children (ages 2 and 6) have not received any hepatitis immunization. Twinrix is currently shorted. Is it okay to just give Hepatitis A to the parents even though the Hepatitis B was 20 years ago? Are the children at risk of Hepatitis B? details
 

Response: Currently boosters of hepatitis B vaccine are not recommended for immunocompetent patients (1,3) so according to guidelines the parents only need Hepatitis A vaccine. Certainly the children are at low risk of Hepatitis B as it is transmitted through close contact with infectious bodily fluids, including through sharing of injection drug equipment (such as needles) and sexual contact.(3) However, there is nothing that can be done anyway as Hepatitis B vaccine is not available.(2) Hepatitis A is more of a concern for the children.
References: 1. https://www.ehealthsask.ca/services/Manuals/Documents/sim-chapter5.pdf
2. PharmaClik
3. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-7-hepatitis-b-vaccine.html#a52

Dec. 6, 2017I am wondering if you can locate any clinical references discussing abuse potential of Vyvanse (lisdexamfetamine) capsules when administered intranasally by snorting. The product monograph notes lower rates of abuse-favoring subjective responses to individuals receiving lisdexamfetamine oral or IV compared with d-amphetamine oral or IV. It also notes that lisdexamfetamine is hydrolyzed in the blood to d-amphetamine, but it does not appear to state if GI absorption plays a role in conversion of the prodrug. I located the following article from 2007 stating that the conversion to d-amphetamine does occur in the GI tract but that the exact mechanism is poorly understood – possibly 1st pass metabolism in the gut lining or liver. (7) This does seem to contradict the Vyvanse monograph somewhat. Is there more current pharmacokinetic information since this publication date? Does lisdexamfetamine truly require GI administration to convert into active d-amphetamine, which could support potentially lower abuse risk via snorting? Are there any case reports of Vyvanse misuse in this regard? Has there been any comparison of abuse risk between Vyvanse and other stimulants, especially when use intranasally? details
 

Response: Hydrolysis studies in human and rat tissues indicate lisdexamfetamine (LDX) is mostly hydrolyzed by red blood cells.(4) While there was some hydrolysis in human kidney homogenate, human liver (lesser extent) and the rat liver, the authors speculate this is due to residual blood. They demonstrated via enzyme incubation that the drug does not undergo CYP metabolism. Also, because there were relatively high levels of LDX in portal blood of rats, one of the conclusions was that, “LDX is primarily absorbed intact in the small intestines into the portal circulation and that enzymatic hydrolysis of LDX occurs primarily in the blood”. I will clarify d-amphetamine levels were detectable in rat portal blood soon after absorption indicating rapid metabolism.
The results above help explain a study comparing kinetic profiles of LDX after oral and intranasal administration.(3) The study was conducted in healthy volunteers in a crossover fashion in which serial blood levels were taken regularly up to 72 hours following a 50 mg dose. There was no difference in the Cmax of d-amphetamine between the two routes (37.6 ng/mL PO; 35.9 ng/ml IN). Tmax was 5 hours following PO and 4 hours following IN.
I found no reports in the literature regarding snorting LDX.
Therefore, the difference is that IN administration does not produce rapid high levels of the abused substance (and, therefore, reinforcement leading to greater misuse) such as the case with other drugs. A person can certainly still abuse LDX by using intranasally, just as one can abuse LDX by taking orally. However, the user will not experience any greater effects between the two routes of administration.
References: 1. https://www.drugbank.ca/drugs/DB01255
2. PM from DPD
3. Intranasal versus oral administration of lisdexamfetamine dimesylate: a randomized, open-label, two-period, crossover, single-dose, single-centre pharmacokinetic study in healthy adult men. Ermer JC, Dennis K, Haffey MB, Doll WJ, Sandefer EP, Buckwalter M, Page RC, Diehl B, Martin PT. Clin Drug Investig. 2011;31(6):357-70. doi: 10.2165/11588190-000000000-00000. PMID: 21539403
4. Pennick M. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. Neuropsychiatr Dis Treat 2010 Jun; 6(1): 317–27 PMID 20628632
5. https://drugs-forum.com/threads/railing-vyvanse.116744/
6. Jasinski DR, Krishnan S: Human pharmacology of intravenous lisdexamfetamine dimesylate: abuse liability in adult stimulant abusers. J Psychopharmacol. 2009 Jun;23(4):410-8.
*PubMed, Scopus "snorting/snort lisdexamphetamine"
7)http://drugtopics.modernmedicine.com/drug-topics/news/clinical/clinical-pharmacology/less-abuse-potential-new-adhd-drug.

Dec. 7, 2017I have an 82 year old female who I am interested in switching from Paxil (paroxetine) to something a little safer, such as sertraline to hopefully improve anticholinergic adverse effects. I am wondering about the tapering regimen to switch from paxil 30 mg (well controlled on that dose) to sertraline. details
 

Patient Age: 82
Patient Sex: F
Medical Problems: “pleghmy” throat, dry eyes resulting in blurred vision and dry mouth - evaluation by ENT found no pathological cause
Medication History: bisoprolol, Nasonex, diazepam (we are presently in the process of tapering off that), pariet, etidrocal and Paxil.
Response: There are several strategies that could be employed including a straight switch, a cross-taper or complete taper of paroxetine before starting and titrating sertraline. I have several examples below. Within each strategy the examples differ by the length of switch.

Considerations for choosing strategy:
- Cross-taper is much more complicated and can be easily executed incorrectly. Ensure patient or caregiver is clear on the instructi or that meds can be compliance packaged from the pharmacy.
- Tapering completely before starting 2nd drug does open the door for return/exacerbation of symptoms as there are several days at low doses.

Considerations for choosing duration:
- Typically quicker switches are used when the original antidepressant is causing severe adverse reaction/allergy. A quicker switch may leave the patient at higher risk of withdrawal symptoms of the original agent. (Note: while we’re substituting SSRI with SSRI, theoretically one should be able to just swap one for the other; however, especially in the case of paroxetine, patients may not tolerate such an abrupt switch.)
- Slower switches hopefully reduce the risk of symptom relapse and adverse effects.
- Considering your patient is well controlled and doesn’t have any life-threatening adverse effects, I would suggest a longer switch duration. That said, one can start with a quicker switch method and, if not tolerated by the patient, lengthen the duration.
1. Straight switch from paroxetine to equipotent dose of sertraline since they are both SSI(5) Paroxetine 30 mg ~ sertraline 75-100 mg(6)
2. Cross taper (2 recommendations):
a. Decrease paroxetine daily dose by 10 mg at weekly intervals; start sertraline at 25 mg daily and increase by 25-50 mg at weekly intervals(1)
b. Cross taper over 1-2 weeks.(5)
3. Taper paroxetine then start sertraline (3 recommendations):
a. Taper paroxetine by reducing dose 25% weekly then start sertralin(4)
b. Taper paroxetine over 2 wee y then start sertraline.(2)
c. Taper paroxetine over 2-5 da y then start sertraline.(3)
References: 1. http://switchrx.ca/antidepressants.php/switch/ad-paroxetine-to-sertraline/Side%20effect-Intolerance-Allergy:%20side%20effect
2. http://wiki.psychiatrienet.nl/index.php/Paroxetine-sertraline
3. clinical Handbook of Psychotropic Drugs, pg 69
4. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-Psyc-Antidepressant.pdf
5. UTD - Switching antidepressants in adults
6. http://www.globalrph.com/antidepressants.htm

Dec. 8, 2017We have a patient with a fungal ear infection - total outer ear canal involved. He has been treated with oral antibiotics but ineffective-that's why the Dr now believes it is fungal. The ear drum is perforated so we can't use locacorten vioform drops. Is there any topical treatment suitable or will we have to go to an oral med? details
 

Patient Sex: M
Medical Problems: otitis externa
Medication History: oral antibiotics
Response: Mainstay of therapy is cleaning of the ear canal by clinician and topical antifungal therapy.(1) Topical antifungals such as clotrimazole 1 % are first line pharmacological therapy. Clotrimazole 1 % cream can be applied twice daily with a swab.(1,2) The azoles are not ototoxic.(3) If oral therapy is needed, fluconazole 200 mg stat, followed by 100 mg once daily for 3 to 5 days is recommended.(4)
References: 1. UpToDate - External Otitis Treatment
2. RxFiles - Common Infections Tx - Otitis Externa
3. Ototoxicity of common topical antimycotic preparations. eLaryngoscope. 2000 Apr;110(4):509-16.
3. Sanfords 2012 pg 12

Dec. 8, 2017I have a question about a drugs of abuse screening test and how long some of these drugs will stay in the system. Do you have a good reference for this? details
 

Response: Some resources:
RxFiles (1); FDA (2); Pharmacist's Letter (3)

I suggested to await the results of Prov. Lab. before taking action as it will provide much more definitive results.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/Urine-Drug-Screening-UDS-QandA.pdf
2. https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/DrugsofAbuseTests/ucm125722.htm
3. PL Urine Drug Testing; Full update February 2014. PL Detail-Document, Urine Drug Testing. Pharmacist’s Letter/Prescriber’s Letter. March 2014.

Dec. 13, 2017Is there an interaction between grapefruit and Eliquis (apixaban)? details
 

Response: Technically this isn't a drug interaction because drug interactions with apixaban warranting caution have been defined as strong inhibitors of either CYP3A4 or Pgp (inhibitors of both are contraindicated).(1) Grapefruit is a moderate inhibitor of CYP 3A4 (1,2). However, because grapefruit is not necessary and apixaban levels cannot be monitored, it would be prudent to avoid grapefruit.
References: 1. http://medsask.usask.ca/documents/newsletters/34.7%20DOACs.pdf
2. Lexicomp
*eCPS, Stockleys (online) does not flag grapefruit, only food; *drugs.com (does not include grapefruit as interacting agent)

Dec. 13, 2017I am doing a medication review for a woman and I have a question about hormone replacement therapy. She is 77 years old. She had a hysterectomy many years ago. She has never had a heart attack or a stroke. She does have A.fib, and when she was diagnosed she says her cardiologist told her to never take estrogen. She was also concerned about the risk of cancer with estrogen. Over the past year she has experienced some pretty severe genitourinary symptoms, including chronic UTI that lasted several months. She saw a specialist who did a scope. The results were that she has atropic vaginal changes and he recommended that she start vaginal estrogen cream. She is afraid to start the Premarin cream because of what her cardiologist said. However, her genitourinary symptoms are bothering her a lot. Can you tell me if the vaginal cream increases her cardiac risk? And if so, by how much? details
 

Response: Here are some statements in the SOGC Managing Menopause Guideline:
- Because systemic absorption of vaginal estrogen is minimal, its use is not contraindicated in women with contraindications to systemic estrogen therapy, including recent stroke and thromboembolic disease. (III-C) However, there are currently insufficient data to recommend its use in women with breast cancer who are receiving aromatase inhibitors (where the goal of adjuvant therapy is a complete absence of estrogen at the tissue level). Its use in this circumstance needs to be dictated by quality-of-life concerns after discussion of possible risks. (III-C)
- For women with signs or symptoms of vulvovaginal atrophy who cannot use estrogens, vaginal dilators, lubricants, and moisturizers should be offered. (III-B)

Furthermore, the 2017 North American Menopause Society Position Statement states (2):
-No excess risk [of venous thromboembolism] has been seen with vaginal estrogen
References: 1. SOGC 2014 Managing Menopause
2. https://www.menopause.org/docs/default-source/2017/nams-2017-hormone-therapy-position-statement.pdf

Dec. 13, 2017Can people be on both atorvastatin and alirocumab? Patient started alirocumab and a few weeks later resumed atorvastatin. details
 

Response: Alirocumab (Praluent) is indicated as an adjunct to diet and maximally tolerated statin therapy.(1, 2)
References: 1. PL Expect New PCSK9 Inhibitors to be Saved as Statin Add-Ons September 2015
2. eCPS

Dec. 14, 2017Is Tecfidera immunosuppressant? Travel Clinic nurse is wanting to know for a patient who may be eligible for some vaccines which are covered for people on immunosuppresants. She has a list from 2011. Tecfidera (dimethyl fumarate) is not on it as it was marketed in 2013. details
 

Patient Sex: M
Response: While there have not been reports of increased infection in patients taking Tecfidera (dimethyl fumarate)(1), it does reduce lymphocyte counts by about 30% (2) and its effect on the immune system is unknown. Therefore, until more is known, it is suggested to avoid live vaccines in patients on this drug.(1-3)
References: 1. Product monograph, eCPS
2. Canadian Pharmacist's Letter 2013; 20(6):290633
3. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2017. Namaka M, Ethans K, Esfahani F. Multiple sclerosis; [updated 01 Apr 2017; cited 15 Dec 2017].Available from: https://www.e-therapeutics.ca/

Dec. 15, 2017Do you have a formula for disulfiram capusules? (500 mg) details
 

Response: There is no formula for capsules. If the dose is large enough to fill a capsule, no diluent is required. (1) Every drug has different fill capacities so it is not possible to determine what size capsule will be best for 500 mg disulfiram; probably size 2-4 for 250 mg. However, based on fill capacities of lactose, ASA, and sodium bicarbonate, likely a capsule size 0 or 1 would be appropriate(1); however, the pharmacist will need to determine this experimentally.
References: 1. Shrewsbury. Applied pharmaceutics in contemporay compounding. 3rd ed, 2008, pg 262

Dec. 18, 2017Is there any specific information regarding timing of flu shot and methotrexate dosing? Would it be better to give mid-week (i.e. 3-4 days after dose). details
 

Response: There are no recommendations as to the timing of vaccines in relation to the methotrexate dose.(1-3,7) Studies did not dictate when the vaccine should be given in relation to methotrexate dose.(4-6)
References: 1. https://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4080407/#!po=61.1111
3. Rheum Dis Clin North Am. 2017 Feb;43(1):1-13. doi: 10.1016/j.rdc.2016.09.003. Epub 2016 Oct 22. Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist. Friedman MA1, Winthrop KL2.
4. Fomin I., Caspi D., Levy V., et al: Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers. Ann Rheum Dis 2006; 65: pp. 191-194
5. Gabay C., Bel M., Combescure C., et al: Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum 2011; 63: pp. 1486-1496
6. Hua C., Barnetche T., Combe B., et al: Effect of methotrexate, anti-tumor necrosis factor α, and rituximab on the immune response to influenza and pneumococcal vaccines in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 2014; 66: pp. 1016-1026
7. Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist. Friedman MA, Winthrop KL. Rheum Dis Clin North Am. 2017 Feb;43(1):1-13. doi: 10.1016/j.rdc.2016.09.003. Epub 2016 Oct 22. Review. PMID: 27890167

Dec. 19, 2017What is the treatment for blastocystis hominis? details
 

Response: If symptomatic, metronidazole or trimethoprim/sulfamethoxazole ( TMP/SMX).(1) Nitazoxanide and iodoquinol are also recommended(1) but are only available through Special Access.(2) [Nitazoxanide is expensive.(2)] This patient has failed after two courses of high dose metronidazole. Suggested Infectious Disease be consulted.
References: 1. Bugs and Drugs app
2. Phone communication with Ashley, Special Services, RUH, 306-655-2280

Dec. 19, 2017Patient (99 year old male) on tamsulosin 0.4 mg BID. He has a catheter that is changed once per month. Is it necessary to be on tamsulosin therapy if he has an indwelling catheter. details
 

Patient Age: 99
Patient Sex: M
Medical Problems: Blood pressure has been low and is fall risk
NH patient - not sure how long has been on tamsulosin
Medication History: coversyl 4 mg, K+ DO, furosemide 40 mg
Response: There is no reason found for tamsulosin in a patient with an indwelling catheter and it has been suggested tamsulosin would not be used for permanent catheterization.(2) While it seems clear the device is a catheter, clarify it is not a urethral stent, which may require tamsulosin treatment for bothersome irritation.(1)
References: 1. UTD - Placement and management of indwelling ureteral stents
2. https://www.pharmacistanswers.com/authors/dr-brian-staiger-pharm

Dec. 19, 2017We have a mom who has read that isotretinoin can cause infertility and is concerned about her 16 year old daughter taking it. Evidence? details
 

Response: One small study found isotretinoin reduced female hormone levels, but did not impact ovarian function.(5) Another small study found reduction of other female hormones that may be used to predict female fertility.(4) The researchers of the latter study recently published results of extended results in which they found the hormone levels returned close to baseline (considered not statistically signficant) after 12 months off the drug, suggesting while isotretinoin may (not confirmed) reduce fertility, it is reversible.
Note that there have been no studies looking at isotretinoin and pregnancy rates.
References: 1. Micromedex
2. Clinical Key - Meyler's
3. Long-term effect of systemic isotretinoin on female fertility. Cinar SL, Kartal D, Aksoy H, Cinar E, Aydin T, Öz L, İmamoğlu H, Ferahbas A, Borlu M. Cutan Ocul Toxicol. 2017 Jun;36(2):132-134. doi: 10.3109/15569527.2016.1172234. Epub 2016 Jul 5. PMID: 27292185
4. The effect of isotretinoin on ovarian reserve based on hormonal parameters, ovarian volume, and antral follicle count in women with acne. Aksoy H, Cinar L, Acmaz G, Aksoy U, Aydin T, Vurdem UE, Oz L, Idem Karadag O, Kartal D. Gynecol Obstet Invest. 2015;79(2):78-82. doi: 10.1159/000371551. Epub 2015 Jan 30. PMID: 25660129

Dec. 20, 2017I have a 26 year old female patient who uses Marvelon for contraception. She has been very pleased with Marvelon as a contraceptive but has been struggling with GI issues, and in particular, she seems very sensitive to dairy/lactose. Apparently lactose is a filler in Marvelon. She is hoping to remain on an OCP. Are you aware of any oral contraceptive options that are lactose free? If not, we plan to switch to the Evra patch. details
 

Response: I’m afraid there are no lactose-free oral contraceptives.(1,4) However, I am skeptical the patient is experiencing symptoms from the lactose content. The amount of lactose in a Marvelon tablet would be < 200 mg (and I think that is an overestimate). There is a study in which people with lactose intolerance were given 400 mg lactose and placebo; there were no differences in subjective symptoms or H2 breath analysis.(2)
If the GI issue is a nausea/vomiting type, I would attribute it to the estrogen content. My first suggestion would be to have her take it at bedtime with a light snack (if she doesn’t already) (3) unless she will not be able to remember to take consistently at this time. The other suggestion would be to switch to a product with lower estrogen content (e.g. Alesse/generics, MinEstrin 1/20).(3) If the GI issues are more diarrhea, again, I would have her try taking at bedtime, or investigate other potential causes.
Of course, she can always switch to the ring, patch or IUD.
References: 1. Allergan Medical Information, Jessica, 1-800-668-6427, Dec 21
2. Montalto M, Gallo A, Santoro L, et al. Low-dose lactose in drugs neither increases breath hydrogen excretion nor causes gastrointestinal symptoms. Aliment Pharmacol Ther. 2008 Oct 15. 28(8):1003-12.
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-OCs-Color.pdf
4. Previous searches

Dec. 20, 2017Fluvoxamine shorted by manufacturer. We were suggesting to switch to fluoxetine but our references suggest a cross-taper. We have no fluvoxamine in stock. What can we do? details
 

Response: Suggested to phone around for stock, but assuming there is no stock, there are not really any choices and a straight switch will be required. While most references do suggest a cross-taper (1-4), one reference does state a straight switch can be considered between SSRIs.(1)
References: 1. UTD - Switching antidepressant medications in adults
2. Clinical Handbook of psychotropic drugs, pg 69
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-Psyc-Antidepressant.pdf
4. switchrx.ca

Dec. 20, 2017I am looking for a recipe for liquid venlafaxine. All I have found is a compound that crushes extended release TABLETS, as far as I can see, the only formulation available is extended release capsules. I'm not sure if this would be interchangeable and if so can I crush the contents of the capsules? details
 

Patient Age: 69
Patient Sex: F
Medication History: PEG tube
Response: Venlafaxine XR capsules can be opened, mixed with water (not crushed) and contents administered through an enteral feeding tube. The tube should then be irrigated with water 2-3 times to facilitate complete transfer of the spheroids. However, to avoid clogging, a 14 or 16 Fr feeding tube is required.(2) I think this may be quite a bit larger than what is typically used.
I did find a formula for 75 mg/5 ml venlafaxine suspension using the spheroids from the capsules.(3) The suspension was prepared by reducing the spheroids to a powder (the authors used a high speed blender) and mixing with either 50:50 OraSweet:OraPlus (OraBlend could be used) or simple syrup. All of the suspensions were stable for 28 days at 5⁰C and 23⁰C. Note that because the venlafaxine is now rendered immediate release, the same daily dose can be given but needs to be provided in 2 or 3 doses per day.(4)
References: 1. Handbook of Drug Administration via Enteral Feeding Tube
2. AHS Alternate Routes of Administration
3. IJPC 2011; 15(1): 81-84 (Note: there is an erratum in IJPC 15(2): 175 but it does not affect this response)
4. Lexicomp
*AHS Compounding

Dec. 20, 2017Client is finishing doxycycline daily (as antimalarial) after trip. She has been prescribed Flagyl 500 mg TID for giardia. Can she take both together? details
 

Response: Yes. There are no interactions. (1-3)
References: 1. Lexicomp
2. drugs.com
3. Stockley's

Dec. 20, 2017Nursing Home wants to know if medications can be crushed. Is there a handy reference? details
 

Response: Referred tomedSask website Drug news.(1)
References: 1. http://medsask.usask.ca/documents/newsletters/30.6%20Guide_to_Medication_Crushing.pdf

Dec. 21, 2017I have a 64 year old female patient with GERD and her physician is looking to treat with a PPI. Pantoprazole 40mg daily was initially prescribed, but upon reviewing the list of non-medicinal ingredients (Sivem brand), the patient declined the prescription due to the presence of triethyl citrate. She states a severe allergy to citrus, citric acid, citrate and any derivatives. She reports experiencing rash and swelling of the lips, face and tongue. She has not ever had allergy testing done. Her physician and I are looking for a recommendation for an alternative PPI that does not use any ingredients relating to the above allergies in the dosage form. details
 

Medical Problems: Allergies: erythromycin, honey, bees, -citrus/citric acid/citrate/any derivatives
Response: I checked the brand names as the generic products seem to have similar ingredients for PPIs.
The following PPIs do not contain any derivative of citrus/citrate:
Prevacid 15 mg, 30 mg (note FasTabs have triethyl citrate); Sivem lansoprazole 15 mg; Losec 20 mg capsules; Losec 20 mg tablets; Sivem Omeprazole 20 mg capsule; Pariet 10, 20 mg (1)
I would strongly suggest this patient see an allergist. As per this exchange on the American Academy of Allergy Asthma & Immunology website, citric acid does not elicit an immunological response. I am not suggesting this patient has not experienced the reaction; however she is unnecessarily avoiding many foods/products. An allergist will be able to determine the source of her allergy and define what does need to be eliminated. (2)
References: 1. eCPS
2. https://www.aaaai.org/ask-the-expert/citric-acid-citrus-allergy

Dec. 22, 20175 month old infant has eczema on back of knees. His mother used HC 1% x 7 days and it resolved but has returned. She has been using Vaseline. Can I suggest she use the HC once or twice a week to keep it at bay with a good moisturizer in between? details
 

Response: To prevent atopic dermatitis, low potency topical corticosteroids can be applied two consecutive days per week with liberal use of moisturizers in between.(2) White petrolatum is an ideal emollient ;(3) suggested "Vaseline" be confirmed as white petrolatum and not a Vaseline brand lotion. The weekly steroid treatment should be reassessed every 3-6 months (2) by discontinuing the steroid and monitoring for recurrences.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/CHT-SteroidClassPotencyCOLOR.pdf
2. https://www.nice.org.uk/guidance/CG57/chapter/1-Guidance#treatment
3. RxTx - Atopic Dermatitis

Dec. 22, 2017Nursing Home nurse called about patient on CBD oil and on Butrans patch. She is wondering if there are any interactions? I don't expect it is well-studied. details
 

Response: There are no known specific interactions (1,2); additive CNS depression can be expected.(2)
References: 1. Stockley's
2. http://www.drugcocktails.ca/medications/buprenorphine

Dec. 22, 2017We have an elder who chewed a Butrans patch - it was found in her mouth. We called PADIS and she is doing fine and does not have pain right now. She was due for a new patch tomorrow. We are wondering if she can start a new patch today - Leland doesn't want her to suffer withdrawal or pain. details
 

Response: If most of the drug were swallowed, it will be akin to removing the patch and not replacing as oral bioavailability is low. (2,3) If some/all of the drug were absorbed buccally and/or sublingually, the half-life is close to that of the patch (27 hours buccal, 37 hours sublingual, 26 hours patch)(1) Since it takes three days for steady state concentrations to be achieved with patch application,(2) a new patch should be placed now and the patient monitored for pain/withdrawal. If the drug were absorbed bucally or sublingually, removing it from the patient's mouth will be similar kinetically to removing the patch from the skin.
References: 1. Lexicomp
2. eCPS
3. Elkader A, Sproule B. Buprenorphine: clinical pharmacokinetics in the treatment of opioid dependence. Clin Pharmacokinet. 2005;44(7):661-80.

Dec. 22, 2017I have a client who needs Bicillin. She is on Seroquel, sertraline and naproxen. Are there any interactions? details
 

Response: No interactions with penicillin.(1,2)
References: 1. Lexicomp
2. drugs.com

Dec. 22, 2017Patient's phenyton levels were low so I got his albumin level. How do you calculate the phenytoin level? details
 

Patient Age: 54
Patient Sex: M
Medical Problems: cerebral lobectomy
phenytoin 32.5 umol/L (=8.21 mcg/ml [1])
albumin 42 g/L = 4.2 g/dL [2]
Medication History: Dilantin 230 mg PO OD
Response: Because his albumin levels are normal, the phenytoin level of 32.5 umol/L is representative of the patient's true free phenytoin concentration (prob ~ 3.25 umol/l).(3) This patient has been on phenytoin at the same dose for quite a long time. His last neurology consult was 2014. Because there is no identifiable cause of the reduced levels the patient should be questioned before increasing the dose. Question whether starting any herbals/OTCs/Rxs? Is he compliant/adherent? Was last draw at same time in relation to dose as usual?
References: 1. http://www.endmemo.com/medical/unitconvert/Phenytoin.php
2. RxTx - Clin Info - Lab Reference Intervals: SI and Traditional Units
3. http://clincalc.com/phenytoin/correction.aspx

Dec. 22, 2017Are there any reports of Guillain-Barre with Tamiflu? Patient has had Guillain-Barre from flu vaccine so no longer gets it and wants to know before taking anything the possibility of causing it again. details
 

Response: No reports were found.(3-6) There is a higher risk of Guillain-Barre Syndrome associated with influenza infection itself than influenza vaccine.(1)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-statement-seasonal-influenza-vaccine-2017-2018.html
2. Micromedex - Guillain-Barré syndrome
3. PM from DPD
4. Lexicomp
5. AHFS
6. Pubmed

Jan. 2, 2018One of our Gastrointestinal residents recently changed a patient from ceftriaxone to cefotaxime for the treatment of spontaneous bacterial peritonitis. Her rationale was that cefotaxime has better penetration than ceftriaxone in the treatment of SBP. (She stated that ceftriaxone is fine for prophylaxis). Is there any evidence for her rationale? Most references list ceftriaxone as a first line treatment option and at RUH we have a policy to change any adult cefotaxime patients to ceftriaxone. Our management is wondering what the evidence is to see if our policy should be reviewed. details
 

Response: 1. There is no strong evidence that one agent is more efficacious than the other, and, empircally, either agent can be considered first-line.
- There is a lack of trials directly comparing the two for efficacy (1,2)
- A Cochrane review found no convincing evidence that 3rd generation cephalosporins have different cure rates for SBP (indirect comparisons) (3)
- There is an on-going trial aiming to directly compare these two antibiotics, but no results have been published yet (4)
- An unpublished research poster abstract (5) concluded the following:
- The resolution ratesof SBP at day 5 were 69.1%, 76.2%, and 76.1% in cefotaxime, ceftriaxone, and ciprofloxacin group. The efficacy was not different between the groups (P = 0.565). The early resolution rate of SBP at 48 hours were 54.5%, 53.1% and 51.9% (p = 0.946). The 1 month mortality after SBP was similar between the groups. (p = 0.628) MELD score (OR
1.074, CI 1.009–1.144, p = 0.026) and the resolution at day 5 (OR 0.251CI 0.094–0.670, p = 0.006) were significant factors for survival. Conclusions: The efficacy of primary antibiotics such as cefotaxime, ceftriaxone, and ciprofloxacin were not significantly different. It is considered that these antibiotics are still efficacious. MELD score and the resolution of SBP at day 5 were most important factors for short term survival.

2. Since there are no clinical studies addressing this, we can look at pharmacokinetic data to try to theoretically understand which one may work better, based on penetration into the ascitic fluid. The available kinetic studies I could find (6-8) suggest that both antibiotics exhibit rapid and complete penetration into ascitic fluid, and both achieve the MIC necessary for all the pathogens present in SBP. On this basis, no recommendation could be made for one agent over the other.
References: 1. UpToDate, Spontaneous bacterial peritonitis in adults: Treatment and prophylaxis
2. Dynamed, Spontaneous bacterial peritonitis in adults
3. Cochrane review comparing antibiotics for SBP: https://www.ncbi.nlm.nih.gov/pubmed/19160207
4. https://clinicaltrials.gov/ct2/show/NCT01265173
5. http://www.journal-of-hepatology.eu/article/S0168-8278(17)31095-4/pdf
6. https://www.ncbi.nlm.nih.gov/pubmed/2776819
7. https://www.ncbi.nlm.nih.gov/pubmed/1748049
8. https://watermark.silverchair.com/16-2-267.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAbwwggG4BgkqhkiG9w0BBwagggGpMIIBpQIBADCCAZ4GCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMbECiXNk1r_vVSB1MAgEQgIIBb-XFq2nZnLtE9J1NRjTyiqiAAkl1uQMU4mOVry7t9PAxzJBOqt7mNtnTGTAGXIZ1ZUcoauiPy8pkVH43PwzF6FEpVsShesrLlzosS0lgX7nc__FBdX_L8576d4aeKikPYj2q0k8eJr6SD_nBhfiRun3zhFUgTvplEprSKNkq_aD0X17iG8_9VrBRfQPUYzQZeSvGMyxdMjDNAlsPsilHRVEox3onp70HT-vazW28WgcXlWpwhFR3OlYUf4Xyc3PWEet5qLMF7noN1gKh5JUttkQ3uOj_xpTjRIwYTsQSe3sgm08KsMe3Cd4rLHB5rfDxRJ7p_Wo2WvdRSdGDlk8Oel57ra3APfTpdZvMsyKU4vSef6Vylx2w_fm-aRRPIh8sqaO3BDvM_zdkUmMRavGjlM4niXptSwvXUTH6hjJxVzZ-zibJnEqdoo4FVYzHd3HDI9y7boGQOAnKwuiY7l-xe5Mz2nrstvZ4Sm-YAGKvMwQ

Jan. 3, 2018Our patient has been prescribed Efudex and is wondering if it will have any detrimental effects on her osteoporosis? details
 

Patient Sex: F
Medical Problems: O/P
hypothyroidism
small lesion on nose
Medication History: risedronate 35 mg once weekly, Synthroid 50 mcg daily
Efudex to be applied once daily
Response: Nothing was found regarding deleterious bone effects of fluorouracil (FU).(1,2) It is possible she did a Google search: the combination of IV FU, cyclophosphamide and methotrexate have been used for breast cancer and has been associated with reduced bone mineral density.(3) It appears the culprit is likely methotrexate (4) However, even if the FU contributed to reduction of bone mineral density (BMD), IV doses of FU are ~ 3720 - 14 880 mg per 28 days.(2) If 1 g (overestimation) of Efudex is applied daily, 50 mg is applied to the skin, of which 6% is absorbed (1) leaving her with systemic expsoure of 84 mg per 28 days.
References: 1. Lexicomp
2. http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Fluorouracil_monograph_1Sep2015.pdf
3. Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Fogelman I, Blake GM, Blamey R, Palmer M, Sauerbrei W, Schumacher M, Serin D, Stewart A, Wilpshaar W. Osteoporos Int. 2003 Dec;14(12):1001-6. Epub 2003 Oct PMID: 14530912
4. http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Methotrexate_monograph.pdf
5. eCPS Efudex

Jan. 3, 2018Patient gets Prolia every 6 months and next dose is due in a couple of weeks. She had a bad infection in November and one of her liver enzymes (GGT) is still elevated (her baseline is 80, the peak was 370, now it's at 151). She is asking about the safety of Prolia with elevated liver enzymes. details
 

Response: Denosumab has not been associated with liver injury or increased liver enzymes, which is in keeping with it's molecular structure in that it is a protein that is largely metabolized to small peptides and amino acids.(1)
References: 1. https://livertox.nlm.nih.gov//Denosumab.htm
2. Liver "function" tests: back to basics - Brenda Schuster. Presentation CSHP-SK AGM 2008 Oct. Hard copy in files

Jan. 3, 2018Patient has been on Lovenox and I have a prescription to switch to Xarelto 20 mg Po OD. How do you switch? details
 

Patient Age: 57
Patient Sex: M
Medical Problems: pulmonary embolism
Medication History: Lovenox 130 mg q12h started Nov 7
Response: A straight switch can be made. The first Xarelto dose can be given at the time the Lovenox dose would have been given. (1)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/CLOT-Rivaroxaban-Checklist-Final-CPP.pdf

Jan. 4, 2018Why can't Zostavax be given IM? details
 

Medication History: Zostavax
Response: The answer is that Zostavax can be administered by the IM or the SC route but the manufacturer chose to use the SC route for the clinical trials so there is more information on SC administration. A recent study however compared the immune response generated by IM and SC administration and found no difference.(1) Shingrix on the other hand should be administered by the IM not the SC route because it contains an adjuvant which can be irritating to the tissues when given SC.(2)
References: 1.Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: A randomised non-inferiority clinical trial
https://www.sciencedirect.com/science/article/pii/S0264410X14016673
2. Ask the Experts: Topics http://www.immunize.org/askexperts/administering-vaccines.asp

Jan. 4, 2018Can cyclosporine cause a retinal bleed? How long does it take until it's eliminated from the system? details
 

Patient Age: 71
Patient Sex: M
Medical Problems: Focal segmental glomerular sclerosis
diabetes
Medication History: coversyl
repeglinide 1mg TID
Response: Based on current evidence cyclosporine does not appear to be associated with an adverse event of retinal bleeds. No case reports have been reported. The elimination half life of cyclosporine ranges from 10-27 hours (average 19 hours). (1) (2)
References: 1. DRUGDEX® System:
Cyclosporine. In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ cited:1/4/2018
2. Clinical Key
3. Pubmed

Jan. 8, 2018What is the reason doctors are ordering antibiotics (especially azithromycin) along with Tamiflu? details
 

Medical Problems: influenza
Response: Don’t use antibiotics for upper respiratory infections that are likely viral in origin, such as influenza-like illness, or self-limiting, such as sinus infections of less than seven days of duration.
References: 1. Efficacy of combination therapy with oseltamivir phosphate and azithromycin for influenza: a multicenter, open-label, randomized study PLoS One. 2014 Mar 14;9(3):e91293 https://www.ncbi.nlm.nih.gov/pubmed/24632748
2. Anti-inflammatory effects of adjunctive macrolide treatment in adults hospitalized with influenza: A randomized controlled trial. Antiviral Res. 2017 Aug;144:48-56. https://www.ncbi.nlm.nih.gov/pubmed/28535933
3. Choosing wisely Canada 2014. Family Medicine. https://choosingwiselycanada.org/family-medicine
4. UpToDate Seasonal influenza in children: Prevention and treatment with antiviral drugs; Treatment of seasonal influenza in adults
5. Seasonal Influenza A(H3N2) Activity and Antiviral Treatment of Patients with Influenza. CDC website. https://emergency.cdc.gov/han/han00409.asp

Jan. 8, 2018Do these patients require an additional booster of vaccine? 1. Hep A - 1st injection Sep 2015, 2nd Jan 2018 2. Twinrix - 1st injection Sep 2015, 2nd, Oct 2015, third Jan 2018 details
 

Medication History: HAV
HBV
Response: No, they don't require an additional booster. In general, regardless of the time between doses, interruption of a vaccine series does not require restarting the series as delays between doses do not result in a reduction in final antibody concentrations for most multi-dose products. However, maximum protection may not be attained until the complete vaccine series has been administered.
References: 1. Canadian Immunization Guide -Part 1 - Key Immunization Information - Timing of VaccineAdministration - Delayed Immunization Schedules - https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-1-key-immunization-information/page-10-timing-vaccine-administration.html#p1c9a2

Jan. 9, 2018Our patient is a 61 year old male with diabetes, arthritis and high cholesterol. He had Pneumovax 23 in 2005 and now his doctor wants to give him Prevnar 13 because of his chronic conditions. Is this is necessary? details
 

Patient Age: 61
Patient Sex: M
Medical Problems: diabetes
high cholesterol
arthritis (rheumatoid?)
Medication History: plaquenil 200mg daily, prednisone 5mg as directed PRN (patient takes 5mg daily)
glyburide 2.5mg daily, januvia 100mg daily, metformin 500mg BID
crestor 10mg daily, altace 10mg daily
allopurinol 300mg daily
Response: Based on the patient's age, medical conditions, medications and pneumococcal vaccine history, there is no indication for Prevnar 13 (Pneu-C-13) at this time. Based on Canadian guidelines, he would only receive one further Pneumovax 23 (Pneu-P-23) at the age of 65+.(1,2) Based on American guidelines, he would receive Prevnar 13 (Pneu-C-13) and another Pneumovax 23 (Pneu-P-23) at age 65+.(4)

In Canada, Pneu-C-13 is only recommended for patients who are immunocompromised or who have had a hematopoietic stem cell transplant.(1,2) Pneu-P-23 is recommended for patients 18 - 64 years who are at high risk of invasive pneumococcal disease; diabetes (DM) is among the conditions lead to high risk.(1,2) No booster doses are recommended in this case (1) but another dose when the patient reaches 65 years would be recommended.(1) As such, there is no indication for Pneu-C-13 for this patient based on Canadian guidelines. Since he has received Pneu-P-23, he just needs another dose once he is 65 years.
In the USA, Pneu-C-13 is recommended for adults who are immunocompromised, have asplenia, cochlear implants, CSF leaks as well as for all patients who are 65+ who have not previously received Pneu-C-13. Pneu-P-23 is recommended also in the cases above after Pneu-C-13, or in patients with DM before age 65 with no use of Pneu-C-13 (as this patient has received). The difference is that the US recommends routine immunization with Pneu-C-13 for those 65+ before the routine Pneu-P-23.(4)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-16-pneumococcal-vaccine.html#tb1
2. http://medsask.usask.ca/documents/hot-topics/Pneumococcal_vaccinations.pdf
3. https://www.cdc.gov/vaccines/vpd/pneumo/hcp/who-when-to-vaccinate.html
4. https://www.cdc.gov/vaccines/vpd/pneumo/downloads/pneumo-vaccine-timing.pdf

Jan. 10, 2018Do Atrovent inhalers still contain peanut residue? I recall years ago this being mentioned. I haven't run across anyone with peanut allergy being put on AStrovent but I'd like to know in case it come up. details
 

Response: The concern with Atrovent inhalers and peanut allergies was the potential for an anaphylactic response to soy lecithin which was historically used in Atrovent inhalers.
(1) Neither soy lecithin nor peanut residues are included in the ingredients of Atrovent currently: contains a solution of ipratropium bromide and the propellant (1,1,1,2 -
Tetrafluoroethane (HFA 134a)), citric acid, ethanol, nitrogen and water.(2)
References: 1. American Academy of Allergy Asthma and Immunology
https://www.aaaai.org/conditions-and-treatments/library/asthma-library/peanut-soy-inhaler
2. Product Monograph from DPD

Jan. 11, 2018It came to our attention that we should find out if cannabis/THC would be a drug interaction with any anti-malarials. Is there literature on this? details
 

Response: While these interactions will not have been studied there have been no reports of interactions reported so as far. There are no interactions between cannabis and chloroquine, mefloquine, doxycycline, or atovaquone/proguanil.(1-4)
References: 1. http://www.drugcocktails.ca/
2. Lexicomp
3. Pubmed
4. Stockley's

Jan. 16, 2018We have a patient with a bad shingles outbreak - this is ongoing in his eye. He is wondering when he would be able to get the Shingrix vaccine. His ophthalmologist told him he may be on valacyclovir for life now (low dose for prevention). Is he eligible to get the vaccine and when should he get it? details
 

Medical Problems: Any patients with hx of HZO in major trials?
Lal H, Cunningham AL, Godeaux O, et al. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med 2015;372:2087-96.
Response: There are two aspects to this case: if revaccination is safe and if so, at what point should it take place.

As for safety, based on a few reports of recurrent herpes zoster ophthalmicus (HZO) following vaccination with Zostavax,(1,2) it has been recommended that patients with a history of HZO not receive Zostavax.(3,4) These recurrences are rare and causality has not been established. Furthermore, this could be limited to live vaccine. However, the major Shingrix trials excluded patients with a history of herpes zoster (5-8) such that we have no data on this situation.

In terms of when to revaccinate if that is decided, the earliest would be following resolution of the active infection.(9) Since recurrence is low in the first 12-18 months following shingles (10) it may be worthwhile to wait at least that long; this would also provide time for more data to emerge regarding the safety of Shingrix in this population.

As a note of interest, it is recommended that valacyclovir be discontinued for a time before and after Zostavax immunization. Shingrix is not live so this precaution is not expected to apply, though there are no direct data to support one way or the other.(11)
References: References:
1. Hwang CW, et al. Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination. Cornea. 2013;32:508–509.
2. Oxman MN, et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med. 2005;352:2271–84.
3. Government of Canada. Part 4 – Active Vaccines: herpes zoster (shingles). Canadian Immunization Guidelines. [updated 01 Mar 2014; cited 17 Jan 2018]. Available at https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html
4. Tuli S, Margolis T. When to avoid the herpes zoster vaccine. Cornea. [2017 Mar; cited 17 Jan 2018]. Available at https://www.eyeworld.org/when-avoid-herpes-zoster-vaccine
5. Lal H, Cunningham AL, Godeaux O, et al; ZOE-50 Study Group. Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults. N Engl J Med. 2015 May 28;372(22):2087-96.
6. Cunningham AL, Lal H, Kovac M, et al; ZOE-70 Study Group. Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older. N Engl J Med. 2016 Sep 15;375(11):1019-32.
7. Grupping K, Campora L, Douha M, et al. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine. J Infect Dis. 2017 Dec 12;216(11):1343-1351.
8. Chlibek R, Bayas JM, Collins H, et al. Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age. J Infect Dis. 2013 Dec 15;208(12):1953-61.
9. CDC. Shingles/herpes zoster vaccination recommendations. Updated November 22, 2016. https://www.cdc.gov/vaccines/vpd/shingles/hcp/recommendations.html (Accessed 17 Jan 2018).
10. Tseng HF, Chi M, Smith N, et al. Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population. J Infect Dis 2012;206:190-6.
11. Pharmacist’s Letter. CHART: Shingles Vaccine: FAQs December 2017

Jan. 17, 2018Rx for uncomplicated active UTI for Bactrim 400/80 BID x 3 days. We phoned MD who said this is an appropriate dose. Is this correct? details
 

Patient Age: 22
Patient Sex: F
Medical Problems: uncomplicated UTI
Response: The dose should be 800 mg/160 mg (i.e. 1 x DS tablets) BID x 3 days (1-5) unless CrCl is 15-30 ml/min in which it is 400 mg/80 mg BID.(3)
References: 1. Bugs and Drugs app
2. MUMS app
3. http://www.rxfiles.ca/rxfiles/uploads/documents/members/ABX-Acute%20Cystitis.pdf
4. RxTx - CPhA Sulfamethoxazole-Trimethoprim monograph
5. UTD - Acute uncomplicated cystitis in women last updated Dec 6 2017

Jan. 17, 2018Healthcare worker had two doses Hep B in 2013. We gave her one dose of Twinrix. I wanted to follow up with two doses of Hep A because she will be travelling but Havrix is shorted. Should we give another 2 of Twinrix? details
 

Response: By receiving two additional doses of Twinrix, the full series of Twinrix will be complete and she will have full immunization for Hepatitis A.(1) The extraneous hepatitis B vaccine she's receiving is not harmful.(2)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-6-hepatitis-a-vaccine.html
2. https://www.cdc.gov/hepatitis/hbv/hbvfaq.htm

Jan. 17, 2018This patient is receiving PLEX 2x/week for 8 weeks total, will any of his medications require adjustments? details
 

Patient Age: 84
Patient Sex: M
Medical Problems: myasthenia gravis
hypertension
Medication History: Azathioprine, Pyridostigmine, Prednisone
HCTZ, perindopril
pantoprazole
Response: There has been very little study on the removal of medications by therapeutic plasma exchange (PLEX). The only drug your patient takes for which I found data is prednisone, in which two case reports have been published. In these cases, the patients were taking prednisone 50 mg and 60 mg daily. Blood samples were taken at various times before, during and after PLEX; this was repeated on a day without PLEX. The authors concluded PLEX removals approximately 1% of the administered prednisone such that replacement is not necessary. (1)

UpToDate suggests azathioprine is removed to some extent, (2) though this statement is not referenced and I was unable to find any research to support the statement. Furthermore, others have theorized azathioprine is unlikely to be removed given its low protein binding (PB) and relatively large volume of distribution (VD); still it is suggested to give the dose following PLEX. (3)

Based on the absence of research, it has been recommended that the removal potential of drugs be estimated based on a PB >80% and/or a VD <0.2 L/kg. (3,4) Below is a table of PBs and VDs of your patient’s drugs (other than prednisone) from Micromedex. (5) Based on these values, neither azathioprine nor hydrochlorothiazide would be expected to be removed, pantoprazole is likely removed, perindopril possibly removed and removal cannot be estimated for pyridostigmine. This said, if it is possible and feasible to administer all his medications following the PLEX session, this may be most prudent.(3,4)
Azathioprine: PB 30%. VD 0.808 L/kg
Pyridostigmine: PB not known; VD 0.53-1.76 L/kg
Prednisone : PB 70%, VD 0.4-1 L/kg
HCTZ: PB 40%, VD 3-4 L/kg
perindopril: PB 60% (prodrug); 10-20% active metabolite. Vd 0.22 L/kg, 0.16 L/kg
pantoprazole: PB 98%, VD 11-23.6 L ( = 0.157-0.337 L/kg for 70 kg patient)
(6)
R
References: eferences:
1. Stigelman WH Jr, Henry DH, Talbert RL, et al. Removal of prednisone and prednisolone by plasma exchange. Clin Pharm. 1984;3(4):402.
2. Kaplan A. Therapeutic apheresis (plasma exchange or cytapheresis): complications. In: UpToDate, Basow, DS (Ed), Waltham MA, 2018. Cited 17 Jan 2018. Available from www.uptodate.com Subscription and login required.
3. Samtleben W, Mistry-Burchardi N, Hartmann B, et al. Therapeutic plasma exchange in the intensive care setting. Ther Apher 2001;5(5): 351–7.
4. Ibrahim RB, Balogun RA. Medications in patients treated with therapeutic plasma exchange: prescription dosage, timing, and drug overdose. Semin Dial. 2012 Mar-Apr;25(2):176-89.
5. DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com (cited: 17 Jan 2018).
6. Lexi-Comp Online™, Hudson, Ohio: Lexi-Comp, Inc.; 2018; cited 17 Jan 201.

Jan. 17, 2018Patient has note that reacted to DuoTrav; Combigan listed in allergies as well. We don't have any nature of the reaction. He has been diagnosed with Atrial fibrillation and MD wants to start atenolol but wants to know the possibility of cross-reaction with the DuoTrav. details
 

Medical Problems: Atrial fibrillation
glaucoma
Response: Without knowing the nature of the reaction, this cannot be adequately answered; most likely, the reaction was an ocular reaction to excipient(s). However, if we assume this was an allergic reaction to the timolol in the DuoTrav, a cross-sensitivity to atenolol is possible as it has been reported (the timolol is systemically absorbed to some extent [2]) and in those with a genuine severe allergy, they should avoid other beta blockers.(1) If this patient had an anaphylactic reaction, it would likely be remembered.
References: 1. Lexicomp -Drug Allergy and Idiosyncratic Reactions
2. DuoTrav PM from DPD

Jan. 19, 2018Is there sesame seed oil in Activis? We have a prescription is for Activis in sesame seed oil. details
 

Response: Yes, the formulation contains progesterone dissolved in sesame seed oil. No compounding required.(1)
References: (1) Teva Medical Information line 1-866-254-6111

Jan. 19, 2018How soon can a patient receive infliximab after completing a course of ciprofloxacin for a UTI? Our protocol states that a patient must wait 5 days after completeing a course of antibiotics before receiving Remicade. details
 

Patient Sex: F
Medical Problems: uti
Medication History: Cipro 500 mg OD - just completed course
Response: I was not able to find any resources stating that infliximab should be withheld after a course of antibiotics.(1)(2) The Janssen Medical Information line agreed that use of Cipro is not a contraindication.(3)
References: 1. Lexi Interadtions
2. LexiComp - infliximab monographn
3. DrugProductDatabase - Remicade monograph
4, Janssen Medical information 1-800-567-3331

Jan. 22, 2018For pharyngitis, one physician routinely suggests gargle with 2 ASA in water – any evidence, guidelines or published anecdotes on this? details
 

Response: Anecdotally, there are some British references which recommend an ASA gargle for sore throat (1)(2) On the other hand, an American site cautions against aspirin gargles, warning that undissolved particles could stick in the throat and cause further irritation to the already inflammed tissue. They recommend warm salt water gargles instead. (3)

The only published evidence involves oral (not gargled) aspirin. These indicate that systemic aspirin is effective in reducing sore throat pain. (4) For example, in a double-blind, placebo-controlled trial of 272 adult patients with acute sore throat associated with other symptoms of upper respiratory infection, aspirin (two 400 mg effervescent tablets in water) reduced the intensity of sore throat pain at two, four, and six hours in the intervention group. (5)
References: 1. http://www.medicaldaily.com/gargling-water-aspirin-could-help-relieve-sore-throats-265083;
2. https://www.uclh.nhs.uk/PandV/PIL/Patient%20information%20leaflets/Sore%20Throats%20and%20Quinsy.pdf
3. https://healthservices.camden.rutgers.edu/topics_sore_throat
4. Symptomatic Treatment of Acute Pharyngitis in Adults – UpToDate
5. Pain Med. 2003;4(2):118

Jan. 22, 2018 Reactions to Cerumol or Cerumenex: what is the reaction from, and is one less likely to have a reaction? details
 

Response: Cerumol contains chlorbutol 5%, oil of terebinth (turpentine) 10%, and paradichlorobenzeen 2% and peanut oil. Turpentine can cause skin irritation. Peanut oil can cause allergic reactions. Health Canada has received a report of anaphylaxis in a peanut-allergic child with use of the commercial product. (1)(2)
Cerumenex which contains triethanolamine popypeptide is no longer marketed in Canaad (3).
References: 1. Impacted Ear Wax - RxTx – CTMA
2. Health Canada. Case presentation: Cerumol and anaphylaxis. Canadian Adverse Reaction Newsletter 2013;23:5. Available from: www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medeff/bulletin/carn-bcei_v23n1-eng.pdf
3. Health Canada Drug Product Database - Cerumenex

Jan. 22, 2018 Are all Nasonex product(s) now non-scented? details
 

Response: Yes – there is just one Nasonex formulation currently marketed in Canada and it is non-scented. (1)(2)
References: 1.Health Canada Drug Product Database
2. Pharmaclik, McKesson Canada catalogue

Jan. 22, 2018 Pertussitreatment – macrolides and trimethoprim/sulfamethoxzaole (TMP/SMX) are first and second line. For someone over age 9, would doxycycline have any coverage? details
 

Response: In vitro susceptibility of B. pertussis to other antibiotic agents including tetracyclines has been demonstrad (1)(2) but in vitro inhibitory activity does not predict clinical effectivenses and this has not been researched, therefore use of tetracyclines is not recommended (3).
References: 1. Expert Opin Pharmacother. 2001;2(8):1275; Antimicrob Agents Chemother. 1998;42(7):1868.;
2. J Antimicrob Chemother. 2000;45 Suppl 1:47: Jpn J Infect Dis. 2014;67(5):345-8)
3. Recommended Antimicrobial Agents for the Treatment and Postexposure Prophylaxis of Pertussis. 2005 CDC Guidelines

Jan. 23, 2018Have you heard of nitric oxide patches for tendinitis? NP has called to see if it is available. details
 

Response: No. I suspect the intended product is nitroglycerin patch which has some evidence for use in chronic tendinopathies. Typically a 0.2 mg/h matrix nitroglycerin patch is cut into quarters or in half and applied to the site. The patch is changed every 24 hours (and, unlike for use in angina, remains applied for 24 hours). (1)
References: 1. RxTx - CTC Sports Injuries

Jan. 25, 2018Should patients get a booster of Zostavax after 5 years? details
 

Response: NACI has no recommendation for Zostavax booster as there has been no research to determine if a booster would be beneficial.(1) That said, immunity is expected to wane after about 5 years; one may want to consider Shingrix.(2)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-8-herpes-zoster-(shingles)-vaccine.html
2. http://medsask.usask.ca/documents/hot-topics/Shingrix.pdf

Jan. 26, 2018Patient would like to check INR at home. Are there good home monitors? details
 

Response: While there may be other monitors, one monitor - CoaguChek by Roche - is available in Canada (2,6,7) and approved by Health Canada.(3) The acquisition cost is $422 for the kit and strips are ~$40/6.(7) The kit is not currently in stock at the Regina distribution centre but the pharmacy can phone McKesson to arrange for order.(8) Some information about INR home testing is available.(4,5) A product brochure and information about the product are available on Roche's website.(6)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/Warfarin%20Management.pdf
2. Levien T. Warfarin Home Monitoring and Patient Self-Management PL Mar 1999
3. Medical Devices Database
4. http://thrombosiscanada.ca/wp-content/uploads/2017/07/Warfain-Point-of-Care-2017Jul21-FINAL.pdf
5. https://www.cadth.ca/sites/default/files/cadth_poc_inr_2.pdf
6. http://www.rochecanada.com/content/dam/corporate/roche-canada/Diagnostics/patients/201405_Coag_XS%20brochure_EN.pdf
7. PharmaClik
8. Phone communciation with Bridget, McKesson Help Desk 1-800-667-9299 Jan 26 2018

Jan. 26, 2018We get a Drug interaction alert between sotalol and Detrol (tolterodine), but not between sotalol and Toviaz (fesoterodine fumarate). Fesoterodine acts as a prodrug and is converted to an active metabolite, 5-hydroxymethyl tolterodine (5-HMT). We are reluctant to suggest this as an alternative. details
 

Patient Age: 70
Patient Sex: M
Medication History: sotalol 80mg BID
Response: Tolterodine has been associated with QT prolongation though fesoterodine has not (1,2) even though it has been reviewed.(2) It is noteworthy that it is possible fesoterodine has simply not been investigated enough for this information to be available.(2) While both fesoterodine and tolterodine are metabolized to 5-hydroxymethyltolterodine (3, 4) perhaps the parent molecule or a lesser metabolite of tolterodine is responsible for the QT effects.
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-QA%20TORSADESdePoint.pdf
2. crediblemeds.org
3. LexiInteract
4. Lexicomp
*Stockley's

Jan. 29, 2018Can pharmacists prescribe for urinary tract infections (UTI) in children? If no, what is the age limit? I looked up the dosage in lexicomp. It's 8mg/kg/day TMP for Sulfamethoxazole-trimethoprim. Can you confirm if that is correct or not? details
 

Patient Age: 2
Patient Sex: F
Medical Problems: UTI
Response: No age limits were set for UTI prescribing as it has been left to the pharmacist’s judgment.(5) So, if all other inclusion and exclusion criteria are met (e.g. a prior UTI has been diagnosed by MD or NP; symptoms are not atypical or subtle), you can go ahead and prescribe. (1)
The dose for TMP/SMX ranges based on reference consulted but the ranges are consistent. For instance, Bugs and Drugs recommends 6-12 mg/kg/day (trimethoprim component) divided BID x 3 days. (2)
However, considering resistance rates are >20% in areas of SK in which they are monitored, nitrofurantoin would be a preferred choice (1) at 5-7 mg/kg/day divided QID x 5 days. (2) Certainly QID dosing is less desirable than BID and if QID will not be possible, go with the TMP/SMX.
References: 1. http://medsask.usask.ca/professional/guidelines/urinary-tract-infection.php
2. Bugs and Drugs App
3. BNF
4. Lexicomp
5. Personal communication with Karen Jensen, author UTI Guidelines, 29 Jan 2017

Jan. 29, 2018Patient was on suppressive valacyclovir 1000 mg once daily for frequent cold sores. She had a couple of outbreaks last week so I want to switch her to famciclovir or acyclovir suppressive therapy. What are the doses? Prefer once daily if possible. details
 

Patient Age: 16
Patient Sex: F
Medical Problems: recurrent mucocutaneous HSV
Medication History: valcyclovir 1000 mg PO OD
Response: Famciclovir has not been investigated for suppression of herpes simplex labialis (5, 6) so no dosing is available.(1-5) Acyclovir can be used at 400 mg PO BID.(1,3)
References: 1. RxTx - CTC herpesvirus infection
2. RxTx - Famvir
3. Bugs and Drugs
4. Lexicomp
5. UTD - Klein R. Treatment of herpes simplex virus type 1 infection in immunocompetent patients\
6. Pubmed - herpes labialis suppression famciclovir

Jan. 30, 2018A man came in with his daughter and says they just got out of the hospital and were told by the dialysis clinic to go in tomorrow in the morning because the girl has diarrhea and she only has one kidney and it isn't working. The doctor said to not take anything until they come back tomorrow but the dad wants to give her something and I don’t know what to tell him. details
 

Medical Problems: Pharmacist knows nothing except she has one kidney and that it doesn’t work and she is on dialysis
Response: Loperamide does not need dosing adjustment in renal impairment however it sounds like the hospital gave explicit directions to return in the morning and not take anything so it would be prudent to follow directions. Electrolytes may not be recommended because of possible hyperkalemia. Not knowing the situation and seeing how there were explicit directions to return to hospital, it would be best to do as hospital told them to do. If she gets worse, please tell them to return to emergency.
References: http://www.nationalkidneycenter.org/chronic-kidney-disease/stages/stage-5/

Jan. 31, 2018Would there be any kind of interaction or contraindication to taking Malarone by someone who is also taking Tecfidera for MS? Live vaccines are contraindicated, but I couldn't find anything against Malarone, but just did very superficial search, so wanted to check with the experts to confirm. details
 

Response: There is no reported nor theoretical interaction between Malarone and tecfidera at this time.(1 - 5)
References: 1. T:\Travel\Travel 2016\Regina\Malaria\Research_Drug Interactions2016 (Extensive analysis of interactions with anti-malarials)
2. Lexicomp
3. Stockley's
4. Guidelines for malaria prevention in travellers from the UK: 2017
5. PubMed "atovaquone tecfidera"; "proguanil tecfidera"

Feb. 1, 2018I have a pregnant patient (26 weeks) with a cold sore. Can I prescribe or do I need to refer? details
 

Response: Referral to MD in pregnancy is not required as per the SK Minor Ailment guidelines for cold sores.(1) Furthermore the following information is available: Pregnancy: acyclovir and valacyclovir can be used during pregnancy; insufficient data available to evaluate famciclovir safety.(1) Caller sounded very reluctant to prescribe; if she is not comfortable prescribing she can refer patient.
References: 1. http://medsask.usask.ca/professional/guidelines/cold-sore.php

Feb. 7, 2018I'm looking for a list of medications that we need to handled with precaution, especially for women of child-bearing age. details
 

Response: Referred to the NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2016.(1)
References: 1. https://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf

Feb. 7, 2018I have not taken the conjuncitivitis training yet. Can I still prescribe for it? Can we bill for this? details
 

Response: The training is optional (3) so a pharmacist can prescribe without undergoing training if s/he feels confident after consulting the guidelines.(3) Conjunctivitis cannot be billed to the Drug Plan.(1)
References: 1. http://medsask.usask.ca/professional/guidelines/conjunctivitis-bacterial,-viral-and-allergic.php
2. http://www.usask.ca/cpdpp/program-essentials/prescribing.php#PracticingPharmacists
3. https://scp.in1touch.org/document/3447/PrescriptiveAuthorityUpdate8.pdf

Feb. 7, 2018Can Celebrex be opened and sprinkled on food for administration? details
 

Response: Yes.(1)
References: 1. AHS Alt ROA

Feb. 14, 2018Is sumatriptan nasal spray available anymore? details
 

Response: GSK is the only manufacturer of sumatriptan nasal spray.(1) The product is listed without inventory at McKesson(3) because it has been on long term backorder.(5) The product is just starting to be released and inventories should be resupplied within the next month.(5) However, Zomig is available as nasal spray and is available.(3)
References: 1. DPD
2. http://ca.gsk.com/media/527922/imitrex.pdf
3. PharmaClik
4. http://www.apotex.com/ca/en/products/search.asp?qt=A2Z&qs=S&t=Search
5. Phone communication with GSK Customer Service, 1-800-387-7374, Feb. 14, 2018

Feb. 14, 2018How do you convert from Strattera to methylphenidate? Patient has been stabilized on Strattera in institutional setting but now in community and it is not covered and EDS criteria are not met. Patient has no Strattera left. details
 

Response: While methylphenidate could be added to atomoxetine, because there is no atomoxetine on hand, this is not an issue. The methylphenidate needs to be started as one would for a new start.(1)
References: 1. https://caddra.ca/pdfs/caddraGuidelines2011Chapter07.pdf

Feb. 15, 2018How long is Gravol stable in a syringe? Home care will be drawing it up. details
 

Response: There are data indicating dimenhydrinate 25, 50, or 100 mg/10ml are chemically stable in polypropylene syringes for 60 days when stored at room temperature or in the fridge with or without protection from light. (1) However, considering the nurses would be drawing the product up at the client's home (outside ISO Class 5), the product is to be used within 1 hour to maintain microbial stability.(3)
References: *Trissel's, Sask IV

Feb. 22, 2018Patient with diverticulitis has been prescribed Cipro 750 mg BID x 7 days + metronidazole 500 mg QID. Bugs and Drugs says BID for the metronidazole. Are there other recommendations that are QID? details
 

Response: Various regimens exist including Cipro 750 mg BID + metronidazole 500 mg BID (1), Cipro 750 mg BID + metronidazole 500 mg QID (2) and Cipro 500 mg BID + metronidazole 500 mg TID.(3) This is likely because there is no high level evidence and the approach is largely based upon retrospective studies and clinical experience.(3)
References: 1. Bugs and Drugs app
2. Dynamed Plus - Diverticulitis
3. UTD - Acute colonic diverticulitis: Medical management

Feb. 26, 2018Physician is requesting a biphasic release of tramadol hcl 200mg tablet. He has Tramadol HCl 200mg extended release 24 hour biphasic 25-75. I do not know of that drug in Saskatchewan/Canada. Are you able to advise me if there is this type available in Canada? details
 

Patient Age: 52
Patient Sex: F
Medical Problems: knee injury
Medication History: tramadol ext release 2x100 mg HS
Response: Both Durela and Tridural are biphasic providing 25% immediate release followed by 75% extended release. Durela is a capsule that contains an IR tablet and ER beads whereas Tridural is a tablet which contains an inner ER core surrounded by an outer IR matrix. Both of these are available as 200 mg dosage forms. (1)
References: 1. http://medsask.usask.ca/documents/hot-topics/Tramadol%20Dosage%20Forms.pdf

Feb. 27, 2018Is there an NSAID that is preferred in breastfeeding? details
 

Response: Because of its extremely low levels in breastmilk, short half-life and safe use in infants in doses much higher than those excreted in breastmilk, ibuprofen is a preferred choice as an analgesic or antiinflammatory agent in nursing mothers.(1)
References: 1. LactMed

Feb. 27, 2018What are some options regarding potassium liquid shortage? Are there any compounding options or tablets that can be used in patients who have trouble swallowing or are on liquid because of reduced GI motility? details
 

Response: There are two products that have inventory, at least for now:
K-Citra liquid. NPN 80011529. Each 5 ml contains 1080 mg potassium citrate (10 mEq K+)
K-Lyte 25 mEq effervescent tablets. DIN 02085992
(1,2)
References: 1. LNHPD
2. PharmaClik

Feb. 27, 2018Patient has tried zopiclone and OTC products for sleep but hasn't been satisfied with any. She was prescribed mirtazapine but it really exacerbated her restless leg syndrome(RLS). What else can be used? details
 

Patient Age: 86
Patient Sex: F
Medical Problems: Getting daytime grogginess with zopiclone
Staying asleep is her problem
Medication History: irbesartan, premarin, progesterone, digoxin, Xarelto, rosuvastatin
Response: Non-pharmacological treatment is key including sleep hygeine (see CTC -Insomnia) and stimulus control (see GeriRxFiles).(1,2) If rosuvastatin is taken at night, patient can switch it to the morning, which may have some effect.(1) Suggested PharmaZZZ program (this pharmacy is actually one of the ones offering it). As for pharmacological treatment, the patient has tried everything and even those are not ideal in the elderly.(1) While the evidence behind melatonin is weak and inconclusive, the harms are minimal.(1,2) Therefore, she could try 1-3 mg (max 5 mg) two to three hours before bed; a sustained release product may help her get through the night without awakening better.(1)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/GeriRxFiles-Insomnia.pdf
2. CTC - Insomnia

Feb. 28, 2018I am looking for information on the safety of apixaban in roux-en-y patients (gastric bypass). All I have been able to find at this time is that there is limited data, to go by case-by-case basis, and that warfarin may be preferred . If possible, can you elaborate and/or provide additional information on the safety and efficacy of apixaban use in roux-en-y patients (Note this patient had the surgery 10 years ago, and requires anticoagulation for stroke prevention AFib – known to have TIAs in the past) details
 

Response: Bariatric surgery, especially Roux-en-y, can result in signficant changes to absorption and other kinetic parameters of drugs.(1,4) The reason for using warfarin as opposed to DOACs is that INR can be monitored. There is next to no information regarding use of DOACs in this population. With removal of parts of the stomach and small intestine, as happens in R-en-Y, absorption of DOACs especially may be affected due to changed in concentrations of Pgp and CYP3A4.(6,7) There have only been two case reports of use of DOACs in patients with bariatric surgery; neither of these was of apixaban in Roux-en-y:
1. Dabigatran in patient who had Roux-en-Y 21 years ago who experienced pulmonary embolism while on dabigatran. His aPTT suggested there was no (or not enough) dabigatran in his system.(6)
2. Rivaroxaban in a patient who had history of recurrent DVT and underwent RYGB. While INRs were not stable before surgery, she had several episodes of bleeding after surgery. She was found to have relatively stable plasma concentrations of the medication, measured by the anti-Xa assay, and therapeutic aPTT/INR at several intervals. Plasma concentrations of rivaroxaban and INR levels peaked at 3 hours with a slow decrease until trough levels were noted. (7)
There is also evidence from one small trial that apixaban aborption may be lower in people of higher body weight (>120 kg) than lower or normal body weight.(4)
It has been suggested that if warfarin absolutely cannot be used and DOACs are required, the drug-specific level be checked (caller thinks this needs to be sent to Toronto), if available; if the levels fall outside the expected range, it is suggested to switch to warfarin rather than adjusting the dose.(4)
References: 1. http://medsask.usask.ca/documents/newsletters/33.1%20Bariatric.pdf
2. PubMed: ("Gastric Bypass"[Mesh]) AND "apixaban" [Supplementary Concept]; ("Gastric Bypass"[Mesh]) AND "Atrial Fibrillation"[Mesh]; - nothing
("Gastric Bypass"[Mesh]) AND "Anticoagulants"[Mesh] - nothing other than [3], which isn't terribly relevant
3. Comparison of Warfarin Dosages and International Normalized Ratios Before and After Roux-en-Y Gastric Bypass Surgery. Steffen KJ, Wonderlich JA, Erickson AL, Strawsell H, Mitchell JE, Crosby RD. Pharmacotherapy. 2015 Sep;35(9):876-80. doi: 10.1002/phar.1632. PMID: 26406775
4. Martin, K. Am J Med 2017; 130(5). http://www.amjmed.com/article/S0002-9343(17)30092-X/pdf
5. https://clinicaltrials.gov/ct2/show/NCT02406885
6. Lachant D. Novel oral anticoagulants after gastric bypass surgery: caveat emptor. Int J Case Rep Images. 2013;4(11):663–665. 2013;4(11):663–665.
7. Thesis - 2016, University of Toledo. - http://utdr.utoledo.edu/cgi/viewcontent.cgi?article=1627&context=graduate-projects
8. http://www.anticoagulationconsulting.com/apps/blog/show/44501583-bariatric-surgery-and-doacs-what-to-do-

Mar. 1, 2018I have some patients coming to see me today for Twinrix vaccinations. They received their yellow fever from travel clinic yesterday. Are there any issues with administering Twinrix today? details
 

Response: Because Twinrix is not a live vaccine(1), it can be administered at any time interval before or after yellow fever.(2)
References: 1. RxTx eCPS
2. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-25-yellow-fever-vaccine.html#p4c24a9

Mar. 5, 2018Our patient is 25 years old. He had 1 dose Havrix in 2009 and hepatitis B through school. No monovalent hepatitis A vaccines are available. How does he finish his hepatitis A vaccination? details
 

Response: Adults who have had one dose of monovalent hepatitis A vaccine can complete the series with 2 doses of Twinrix.(1)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-6-hepatitis-a-vaccine.html

Mar. 5, 2018What is the signifance of the interaction between metoprolol/citalopram. details
 

Patient Age: 58
Patient Sex: M
Medication History: metoprolol 12.5 mg BID
citalopram 10 mg
Response: Citalopram may increase the levels of metoprolol, thereby reducing its cardioselectivity.(1) However, the citalopram dose is low and citalopram is among the SSRI less likely to cause the interaction.(1) Furthermore, this patient's metoprolol dose is extremely low and he was on this combination - seemingly without trouble - a year ago. That said, the metoprolol levels may increase such that his heart rate and blood pressure should be monitored.
References: 1. Stockley's
2. Lexicomp

Mar. 6, 2018 We have a patient with celiac disease and as well must avoid cornstarch, dairy (includes casein and whey). Is there an SSRI available that does not contain these ingredients? details
 

Medication History: sertraline APX and PMS gives her hives
Response: It is doubtful any solid oral dosage form is going to be free from lactose and cornstarch. For instance, all of the APX brand SSRIs contain lactose.(1) However, Apo fluoxetine 20 mg/5ml solution contains benzoic acid, glycerin, natural mint flavor, purified water and sucrose.(1)
Caller also mentioned Cipralex Meltz, which would also be acceptable,(5) though are not on the drug plan.(6)
Caller is going to investigate fluoxetine solution.
References: 1. apotex.ca/products
2. medisca.ca
3. xenexlabs.com
4. PharmaClik
5. eCPS
6. SK Formulary online

Mar. 8, 2018I have a question about combining diltiazam and apixaban . Patient just got discharged from the hospital and wants to start on both - I know they interact - is this signficant - should they be decreasing the apixiban dose? details
 

Patient Age: 46
Patient Sex: M
Medical Problems: A fib, possible MI
Medication History: nitroglycerin spray
atorvastatin 40
apixaban 5 mg BID
diltiazam 240 od
metoprolol 100 BID
Response: While diltiazem does increase apixaban levels, the increase has not been associated with bleeding and is not considered clinically relevant.(1,2) The patient's heart rate and blood pressure should be monitored because of the additive cardiac depressant effects of beta blockers + calcium channel blockers as well as the fact that diltiazem may slightly increase metoprolol levels; this is not a reason to avoid the combination.(1,2)
References: 1. Stockley's
2. Lexicomp

Mar. 9, 2018Our patient received the first dose Gardasil 9 about a year ago and is now coming in for 2nd and 3rd. Does she need to restart? details
 

Response: The series does not need to be restarted. She can get the 2nd dose now and the last one at least 12 weeks after the 2nd dose.(1)
References: 1. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-9-human-papillomavirus-vaccine.html#a5_e

Mar. 16, 2018A child was prescribed Clavulin last night for otitis media from a walk-in clinic. The maximum dose of amoxicillin was prescribed and today the MD asked if the clavulanate amount is appropriate. Clavulin 400 was dispensed and patient is getting 7.5 ml BID. Child had been on clavulin end of January; end of Febuary amoxicillin; yesterday Clavulin. Child weighs 13 kg. details
 

Patient Age: 2
Medical Problems: 20 month old
13 kg
OM in Jan tx'd with std dose Clavulin; OM in feb tx'd with hgih dose amoxi
Response: Clavulin 400 contains 400 mg amoxicillin and 57 mg clavulanate per 5 ml(1) so the child is receiving 600 mg/85.5 mg per dose and 1200 mg/171 mg per day. The clavulanate component exceeds the recommended maximum daily dose of clavulanate of 10 mg/kg.(1) As such, the prescription should be dispensed again as Clavulin 400 + amoxicillin to make up 200 mg per dose.
References: 1. http://medsask.usask.ca/documents/newsletters/34.5%20AmoxiClav.pdf

Mar. 19, 2018We have a patient who is on Eliquis (apixaban) 5 mg BID for Atrial Fib. The patient's doctor sent a fax with a renewal of Eliquis with a note asking if he should continue on Eliquis and ASA 81 mg OD. What do we tell the patient and doctor? details
 

Response: Use of both ASA and Eliquis is appropriate if there is an indication for ASA (since the indication for Eliquis has been confirmed).
Indications for ASA include:
Secondary prevention in: acute coronary syndrome, coronary artery disease, cardiovascular disease, angioplasty, coronary artery bypass graft. There are other secondary preventive uses with less evidence.
In terms of primary prevention of MI, recommendations vary but typically lean toward not using. Regardless, an assessment of risk versus benefit would be recommended and the Eliquis certainly increases risk here.
(1)
References: 1. http://www.rxfiles.ca/rxfiles/uploads/documents/members/cht-AntiThrombotics.pdf

Mar. 20, 2018Is metoprolol succinate available in Canada? details
 

Response: No, only metoprolol tartrate.(1)
References: 1. DPD

Mar. 20, 2018Is Finacea gel safe in pregnancy? details
 

Response: The risk is likely low given minimal systemic absorption following topical use (<4-8%).(1,2) However, no human data were located (1-4) and animal reproductive study results are unclear.(1,2)
References: 1. Lexicomp
2. Schaeffer
3. Micromedex - no reproductive data
4. Briggs - not listed

Mar. 21, 2018In regards to testing for B12 levels while on Metformin, do you know of any guidelines of the frequency of testing? details
 

Response: Routine testing of B12 levels for metformin patients is not recommended but levels can be checked every 2-3 years or every 1-2 years in those at risk of developing B12 deficiency (e.g. PPI users, vegetarians, elderly) or in those who are experiencing worsening peripheral neuropathy. Severe B12 deficiency may cause peripheral neuropathy which may be mistakenly attributed to progression of diabetes. (1)
References: 1. http://medsask.usask.ca/documents/newsletters/34.4%20Drug-Induced%20Nutrient%20Deficiencies.pdf