Chronic Treatment with Proton Pump Inhibitors: Rationale Therapy or Unnecessary Drugs?

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Proton pump inhibitors (PPIs) constitute a class of drugs used short-term (4-8-weeks) to provide a pronounced and prolonged reduction in gastric acid production allowing gastric and duodenal ulcers to heal.  They are also indicated for short-term management of non-erosive gastroesophageal reflux disease (GERD) and erosive esophagitis.  They are also used for 10-14 days (or up to 32 days if ulcer present) in conjunction with antibiotics to eradicate Helicobacter pylori (H. pylori) infections.  Finally PPIs may be indicated for long-term treatment in patients with refractory GERD and hypersecretory conditions including Zollinger-Ellison Syndrome.

PPI drugs include omeprazole (Pilosec, Prilosec-OTC), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix), rabeprazole (Aciphex), and deslansoprazole (Dexilant, Kapidex).  PPIs should be dosed 30-60 minutes prior to breakfast to manage the gastric acid surge seen in the morning.  These drugs are widely used and Prilosec and Prevacid are available without a prescription.  Also, the use of PPIs has largely replaced surgery as the primary treatment for gastric and duodenal ulcers.

However, data suggests that up to two-thirds of PPI use may be inappropriate.  PPIs are routinely used in hospitals for stress ulcer prophylaxis, but only one-third of hospitalized patients actually need them.  Rebound acid hypersecretion is found in 60-90% of patients using a PPI for more than 2-3 weeks.  Symptoms of rebound hypersecretion (dyspepsia, heartburn) may persist for 3 months or more and encourage the continued use of PPIs.  Rebound hypersecretion may be reduced or eliminated by tapering the PPI dose slowly over 4-6 weeks and/or stepping down to treatment with a histamine-2 (H2) blocker such as ranitidine (Zantac) or famotidine (Pepcid) for 4-6 weeks and then discontinue.  Antacids may also be used as need to control symptoms during this time.

Drug Interactions

PPIs are implicated in a number of clinically significant drug interactions including a 20-40% reduction in antiplatelet activity when clopidogrel (Plavix) is used with omeprazole or esomeprazole.  Use of these PPIs with clopidogrel is contraindicated per product labeling.  Also, because they lower gastric pH (acidity) they may reduce the absorption of calcium, iron, magnesium, and Vitamin B-12.  If calcium must be given with a PPI, the calcium citrate formulation is recommended as its absorption is less affected by the higher gastric pH produced by PPIs.

Safety Concerns

There is concern that PPIs may increase fracture risk in both men and women and they have been implicated with a 25% increase in overall fractures and a 47% increase in spinal fractures in postmenopausal women.  Any patient who must remain on long-term PPI therapy who is a risk for factures (i.e. osteoporosis or osteopenia) should receive supplementation with adequate doses of calcium citrate and Vitamin D.

PPIs also increase the risk of infection with bacteria including Clostridium difficile and those causing pneumonia that tend to proliferate when gastric pH remains elevated.  In fact, patients being treated for C. difficile infections while taking a PPI are at a 42% increased risk for recurrent infection within 90 days.

Never stop taking any medication without first consulting with your prescriber.  Abrupt discontinuation of these medications can cause rebound hypersecretion of stomach acid.



  1. Proton Pump Inhibitors: Appropriate Use and Safety Concerns.  Pharmacist’s Letter/Prescriber’s Letter.  May 2013 Detail Document 290510.
  2. Proton Pump Inhibitors and Rebound Acid Hypersecretion. Pharmacist’s Letter/Prescriber’s Letter.  2009; 25(9):250920.