The Safety of Appropriate Use of Over-the-Counter Proton Pump Inhibitors: An Evidence-Based Review and Delphi Consensus

Abstract

The availability of over-the-counter (OTC) proton pump inhibitors (PPIs) for the short-term (2 weeks) management of frequent heartburn (≥2 days/week) has increased markedly, yet evidence-based recommendations have not been developed. A panel of nine international experts in gastroesophageal reflux disease developed consensus statements regarding the risks and benefits of OTC PPIs using a modified Delphi process. Consensus (based on ≥80% approval) was reached through multiple rounds of remote voting and a final round of live voting. To identify relevant data, the available literature was searched and summarized. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system terminology was used to rate the quality of evidence and strength of recommendations; consensus was based on ≥2/3 agreement. After 4 rounds of review, consensus was achieved for 18 statements. Notably, the available data did not directly reflect OTC use, but instead, prescription use; therefore, extrapolations to the OTC setting were often necessary. This limitation is regrettable, but it justifies performing this exercise to provide evidence-based expert opinion on a widely used class of drugs. The panel determined that using OTC PPIs according to label instructions is unlikely to mask the symptoms of esophageal or gastric cancer or adversely impact the natural history of related precursor conditions. OTC PPIs are not expected to substantially affect micronutrient absorption or bone mineral density or cause community-acquired pneumonia, Clostridium difficile infection, or cardiovascular adverse events. However, OTC PPI use may be associated with slightly increased risks for infectious diarrhea, certain idiosyncratic reactions, and cirrhosis-related spontaneous bacterial peritonitis. The available evidence does not suggest that OTC PPI use consistent with label instructions is associated with substantial health risks. To minimize potential risks, healthcare professionals and consumers must actively participate in decision making when managing reflux-related symptoms in the self-care setting.Electronic supplementary materialThe online version of this article (doi:10.1007/s40265-017-0712-6) contains supplementary material, which is available to authorized users.

A Systematic Review of Gastric Acid-Reducing Agent-Mediated Drug–Drug Interactions with Orally Administered Medications

“…Common PPIs include omeprazole, esomeprazole, lansoprazole, dexlansoprazole, pantoprazole, and rabeprazole, with many of these being available without a prescription [2,[10][11][12][36][37][38]. PPIs irreversibly bind and inactivate the proton pump (i.e., the hydrogen/potassium adenosine triphosphatase system) at the secretory surface of gastric parietal cells.…”

“…Although several review articles have been published discussing gastric acid-related DDIs mediated by coadministration of antacids [1], H 2 RAs [9], or PPIs [2,[10][11][12], these reviews are not sufficiently comprehensive in capturing all documented DDIs with ARAs and tend to focus on gastric pH-dependent DDIs and/or basic drugs. Subsequently, several new drugs have been approved, and new information is available in the literature.…”

Are we missing tracks while prescribing proton pump inhibitors? - An opinion from clinicians cross sectional hospital based questionnaire study

“…The availability of PPIs as an OTC drug and it's over utilization by common and normal people for multiple disease backgrounds with or without symptoms has subjected patients to a potential risk such as parietal cell hypertrophy, enterochromaffin like cell hyperplasia and hypergastrinemia leading to rebound acid secretion. 2 To avoid this to happen, there needs to be a contemplation on how to best use these agents safely and effectively. Additionally, there is a need for guidelines for pharmacy use to assist with safe and effective treatment of reflux symptoms with OTC PPIs and lastly, patient education and awareness is a must 10 as most of them end up selfmedicating themselves.…”

Alternative therapies for GERD: a way to personalized antireflux surgery

“…PPI therapy does treat some symptoms of GERD but not its cause. Even if these symptoms respond to medical therapy, PPIs have come under scrutiny due to eventual long‐term adverse events . Although several clinical studies have shown a cancer‐protective effect of PPI, data remain contradictory .…”

“…Even if these symptoms respond to medical therapy, PPIs have come under scrutiny due to eventual long-term adverse events. 2 Although several clinical studies have shown a cancer-protective effect of PPI, data remain contradictory. 3 As apparently only a very small proportion of GERD patients are finally treated by conventional antireflux surgery, a large therapeutic window of patients, who are not effectively treated with PPI but do not want to run the potential risks of conventional surgery, remains.…”