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 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. 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. 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. 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. 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, 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, 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, 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. 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. 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. 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. 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. 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, 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, 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. 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, 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, 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, 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, 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, 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, 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. 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, 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, 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, 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. 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. 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. 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, 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. 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, 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 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, 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. 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, 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. 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. 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, 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, 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, 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. 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, 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 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, 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. 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, 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, 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, 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, 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, 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