Gastroesophageal Reflux Disease (GERD) - Guidelines for Prescribing H2RAs and PPIs

Description
  • Most common acid-related condition in Canada. Approximately 10% to 20% of people in developed countries suffer from GERD. It can affect children and infants as well as adults.
  • Classic symptoms are heartburn and regurgitation.
  • Caused by a number of mechanisms, the most important being a transient relaxation of the lower esophageal sphincter. Increased lower abdominal pressure, reduced lower esophageal sphincter tone, delayed gastric emptying, and impaired esophageal clearance may also be involved.
  • Risk factors:
    • Being overweight or obese
    • Diet
    • Pregnancy
    • Smoking
    • Other conditions: crohn’s disease, celiac disease, hypothyroidism, hypercalcemia
    • Use of medications which reduce lower esophageal pressure can induce or worsen GERD – alpha-adrenergic antagonists, anticholinergics, beta-agonists, benzodiazepines (diazepam), calcium channel blockers (nifedipine, felodipine, amlodipine), nicotine, progesterone, theophylline
  • For more information go to:
    • RxTx. CTC - Gastroesophageal Reflux - Available at SHIRP.
    • American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease. Gastroenterology 2008;135:1383–1391. Available at National Guideline Clearinghouse.
Signs and Symptoms

GERD

  • Heartburn: a burning sensation behind the breast bone that may rise to the back of the throat.  Symptoms may wax and wane in intensity. Often worse when lying down, bending over, or after a meal.
  • Regurgitation of acid or bile that may rise to the back of throat.
  • Hypersalivation (water brash).
Mild:  symptoms are not overly bothersome to the patient and infrequent (2 or fewer times weekly); if mild symptoms are frequent but not particularly bothersome, they do not have to be treated as moderate.  Ask patient for preference. 

Moderate:  more frequent (> 2  times weekly), more intense or prolonged symptoms; patient would rather take daily medication than experience symptoms.

Differential Assessment

Diagnosed based on the presence of the typical symptoms described above. Most patients do not require further investigation but an by the patient's primary care provider assessment should be recommended if the following conditions are suspected.

  • Cardiac disease - pain is typically central and squeezing in nature, may radiate up into the neck, shoulder, or down the arm. Often associated with breathlessness/sweating.
  • Peptic ulcer disease, malignancy - see alarm symptoms below in "When to Refer".
  • Medication-induced reflux - see list above of medications which increase the risk of GERD.
  • Medication-induced esophagitis - use of bisphosphonates, clindamycin, ethanol, iron, NSAIDs (including ASA and celecoxib), quinidine, potassium chloride, tetracyclines.
  • Functional dyspepsia - symptoms such as abdominal pain and fullness in addition to heartburn and regurgitation symptoms.
  • Biliary disease – upper abdominal discomfort / pain beneath the centre or right side of the sternum. Symptoms may follow large or fatty meals and may include nausea and vomiting.
When to Refer
  • Alarm symptoms - Refer to patient's primary care provider in a timely manner if any of the following are present:
    • Chest pain typical of cardiac event - pain radiating to shoulder, neck, arm, shortness of breath, sweating – refer for immediate medication attention
    • Recurrent vomiting
    • Signs of gastrointestinal blood loss (hematemesis, melena, anemia)
    • Dysphagia (difficulty swallowing), especially solids
    • Odynophagia (severe pain on swallowing) – strictures
    • Unexplained weight loss > 5%
  • Unexplained cough, dyspnea, hoarseness
  • Severe symptoms such as frequent noctural disturbances and/or regular interference with daily activities.
  • Age < 18 years old 
  • Age > 50 years old with new onset of undiagnosed (by physician) symptoms
  • Potential for drug-induced GERD - if prescribed medication is suspected, refer to patient's primary care provider, or contact patient's primary care provider with an alternative medication option; if over-the-counter product is suspected, advise patient to discontinue and monitor for resolution of symptoms.
  • Unable to confirm patient self-diagnosis - symptoms require further evaluation and /or supervised treatment.
  • Pregnancy
Treatment

Non-pharmacological Treatment

It is important to individualize non-pharmacological approaches to target the factors which appear to be contributing to the symptoms; lifestyle changes are unlikely to be very effective in severe GERD but are still recommended as they contribute to general good health. 

  • Avoid foods / beverages that worsen or trigger symptoms (e.g. caffeine, chocolate, onions, peppermint, tomatoes, high-fat foods, over-indulgence in alcohol)
  • Eat small meals and chew food well
  • Don’t lie down for 2 -3 hours after eating
  • Avoid tight clothing
  • Encourage smoking cessation
  • Elevate head of bed frame (i.e. not extra pillows)
  • Achieve ideal body weight

Over-The-Counter Drug Options

  • Antacids, alginates; over-the-counter dose H2 receptor antagonists (H2RAs); OTC-dose H2RAs/alginate combination
    • mild, infrequent symptoms
  • Esomeprazole 20 mg or omeprazole 20 mg (14 days)
    • mild and frequent symptoms (if daily treatment is preferred) or moderate symptoms.  PPIs are considered first line.  Grade A recommendation (consistent high-quality evidence)
    • on-demand therapy for recurrent symptoms appearing 3 months after resolution of last episode
      • esomeprazole or omeprazole is taken daily until symptoms subside, then discontinue
    • intermittent therapy for recurrent symptoms appearing 3 months after resolution of last episode
      • esomeprazole or omeprazole is taken daily for a pre-determined amount of time (e.g. 2 - 4 weeks) then discontinued

Prescription Drug Options

  • H2RAs
    • infrequent symptoms that improved but not resolved by PRN OTC treatment
    • prescribe x 14 days.  May repeat x1.
  • Rx PPIs
    • frequent (>2 times weekly) and/or moderate symptoms
    • PPIs are considered first line. Grade A recommendation (consistent high-quality evidence).


Lactation
:  No special precautions are required with H2RAs. Limited information suggests low levels of PPIs are secreted in breastmilk; no adverse effects have been reported in nursing infants.

Advice / Monitoring

Advice

  • Recommend appropriate non-pharmacologic measures.
  • Advise patients that antacids and alginates usually provide immediate relief of symptoms.
  • Expected onset of effect for H2RAs is 30 – 60 minutes and for PPIs onset may be within 3 hours, although maximum effect may take up to 4 weeks. 
  • For patients with predictable symptoms (e.g. after a larger than normal meal, spicy food) recommend one or two doses of an OTC-dose H2RA to be taken 30 – 60 minutes before the trigger.
  • PPIs may have maximal effect if taken within 30 minutes of meal; however, if patient takes at another time and experiences relief, it is not necessary to change the timing
  • PPIs induce remission more frequently than H2RAs.
  • Tachyphylaxis to the effects of H2RAs for GERD may occur within one month if taken regularly; this has not been documented with PPIs
  • The various PPIs have similar effectiveness and safety profiles when given at equipotent doses (See Table 1 under "Products").
  • If symptoms return after discontinuation of treatment, on-demand  or intermittent PPI therapy is acceptable. 
  • Caution patients that some may experience rebound acid hypersecretion upon discontinuation of PPIs.  This has not been well-established, especially after short term PPI use; however, it can be managed by PRN use of an H2RA +/- antacid and possibly by tapering PPI at the end of treatment. 
    • If symptoms return within 7 days of PPI discontinuation, consider rebound and reinitiate therapy to taper.  No particular tapering regimen can be recommended.

Assess Benefit:

  • Reassess for any alarm symptoms that would indicate need for more urgent referral to patient's primary care provider at each follow-up.
  • If at any point symptoms worsen, refer to patient's primary care provider.
  • Follow-up in 2 weeks.  If symptoms are not resolved with PRN OTC treatment:
    • try a different PRN OTC product  OR
    • prescribe H2RA x 14 days
  • Follow-up in 2 weeks. If symptoms are not resolved and the patient is using an H2RA:
    • prescribe PPI x 28 days.
  • Follow-up after initial PPI therapy (28 days)
    • If no improvement of symptoms, ensure proper administration.  If taken properly, refer to patient's primary care provider for H. pylori testing or other investigations.  PPIs and H2RAs need to be discontinued at least 1 week but preferably longer before undergoing urea breath testing (UBT) to ensure accurate results. 
    • If symptoms improve but not resolved, repeat PPI x 28 days
    • If symptoms resolved, discontinue or, if patient prefers, repeat PPI x 28 days
  • Symptom recurrence
    • If at least 3 months after last episode, consider a new, discrete episode and treat with therapy that was previously effective.  If patient was taking PPI, consider on-demand or intermittent therapy; OTC esomeprazole or omeprazole are useful in these cases.
    • If within 7 days since discontinuation of a PPI, consider possibility of rebound hyperacidity and prescribe rx PPI or recommend OTC esomeprazole or omeprazole with instructions to taper over a couple of weeks. If rebound is ruled out, contact or refer patient to patient's primary care provider for consideration of maintenance therapy.
    • If symptoms recur more than 7 days but less than 3 months since discontinuation, refer patient to their primary care provider for consideration of maintenance therapy.

Assess Adverse Effects

  • H2RA side effects are usually well tolerated - diarrhea, headache, dizziness, rash, and tiredness have been reported. If persistent or very bothersome, discontinue and consider alternate therapy or refer to patient's primary care provider.
  • PPI side effects are usually mild and reversible - headache, diarrhea, nausea, abdominal pain, constipation, dizziness, and skin rashes. If persistent or very bothersome, discontinue and consider alternate therapy or refer to patient's primary care provider.
  • Long-term use of PPIs (1 year or longer) can rarely cause hypomagnesemia.  If a patient has taken a PPI daily for more than 1 year and is experiencing muscle cramps, palpitations, tremor, and/or dizziness, consider recommending rmagnesium levels be checked.
  • Other possible long-term safety issues of PPIs include pneumonia, osteoporosis, Clostridium difficile, and vitamin B12 malabsorption, but risk is very low.
Products

Detailed information on contraindications, cautions, adverse effects and interactions is available in individual drug monographs in the CPS (e-CPS), Lexi-Comp, AHFS, www.drugs.com or other reliable drug monograph references. For comprehensive drug comparisons, see RxFiles charts (www.rxfiles.ca).  This information should be routinely consulted before prescribing.


Table 1: Doses of H2-Receptor Antagonists (H2RAs)
and Proton Pump Inhibitors (PPIs) for Treatment of GERD
Drug Dose
H2RAs Over-the-Counter§
Famotidine 10–20 mg once. The 10 mg dose may be repeated after 1 hour if needed.
Ranitidine 75–150 mg once. May repeat a dose if needed after 1 hour
75–150 mg 30–60 minutes before eating
H2RAs Prescription 
Cimetidine*

800 mg BID or 300–400 mg QID with meals and at bedtime

Famotidine

20 mg BID

Nizatidine

150 mg BID

Ranitidine 150 mg BID
PPIs OTC
Esomeprazole

20 mg once daily (14 day limit)

Omeprazole

20 mg once daily (14 day limit)

PPIs Prescription

Esomeprazole (EDS)¥

20 mg once daily

Lansoprazole

15 mg once daily

Omeprazole (all forms) 20 mg once daily
Pantoprazole (Na & Mg)   40 mg once daily
Rabeprazole 10 to 20 mg once daily
§ If famotidine and ranitidine are given at low doses for PRN usage, that is considered OTC usage and is not eligible for the assessment fee.
*Cimetidine inhibits the metabolism of many drugs; caution advised before prescribing
¥EDS requirement is diagnosis of GERD by physician - only a physician can apply in this situation. 

Prescribing and Billing Details
  • pseudoDIN: 00951096
    • Max of 3 claims per 365 days per patient

  • May prescribe 28 days' worth of treatment with one refill.
    • Refill to be provided after follow-up  in 28 days if improvement, but not complete resolution, is noted.

  • If an OTC strength of ranitidine or famotidine is chosen (i.e. prn usage recommended), it will NOT be eligible for the assessment fee.

  • You may still prescribe EDS products (esomeprazole magnesium trihydrate), but the drug plan will not cover the medication.  Only a physician may apply for EDS in this case, as a physician diagnosis of GERD is required.  The assessment fee will still be covered.

  • Only products with an official indication from Health Canada for GERD are considered for these guidelines.  Only the active ingredients in the "products" section are approved for pharmacist prescribing.  
Treatment Flowchart
Pharmacist Assessment Documents
References / Suggested Reading
  1. RxTx[Internet]. Ottawa (ON): Canadian Pharmacists Association; 2016. Shaffer EA.  Gastroesophageal reflux disease; [updated 01 Sep 2016; cited 22 Nov 2016]. Available from http://www.e-therapeutics.ca   
  2. Schuster B. Gastrointestinal ‐  Acid Suppression Drugs: Evidence, Tips And Pearls.  RxFiles Comparison charts. 10th ed. Saskatoon, SK: Saskatoon Health Region. [updated 01 May2015; accessed 22 Nov 2016]. Available from: www.RxFiles.ca
  3. Armstrong D, Marchetti N. Canadian Pharmacists Journal 2008; 14 (Suppl 1): S10-15. Available at www.cpjournal.ca.
  4. Emedicine. Gastroesophageal Reflux Disease. Available at http://emedicine.medscape.com/article/176595-overview.
  5. American Pharmacists Association. OTC Advisor: Selfcare for gastrointestinal disorders. Jan. 15, 2010.
  6. American Gastroenterological Association Medical Position Statement on the Management of Gastroesophageal Reflux Disease. Gastroenterology 2008;135:1383–1391. 
  7. 2013. ACP Smart Medicine (SM) & AHFS DI® Essentials™. Philadelphia, PA. American College of Physicians. STAT!Ref Online Electronic Medical Library. http://online.statref.com/Document.aspx?fxId=539&docId=1217. 2/26/2014 10:23:04 AM CST (UTC -06:00).
  8. Kahrilas PJ. Medical management of gastroeophageal reflux disease in adults. In: UpToDate, Basow, DS (Ed), UpToDate.  Waltham MA, 2014.  Available from www.uptodate.com  Subscription and login required.

Prepared by medSask.
Reviewed by Dr. D.G. Bishop, Family Physician and Dr. Brenda Schuster, PharmD.
Funded by the Saskatchewan College of Pharmacy Professionals
Posted May 2010. Updated May 2017.