Proton pump inhibitors (PPIs) are proven medications of choice for gastroesophageal reflux disease (GERD), acid-related disorders, erosive esophagitis, Barrett esophagus, prevention of gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs, eosinophilic esophagitis, peptic ulcer disease, stress ulcer prophylaxis in critically ill patients, and other indications. Best practice guidelines from several sources on the appropriate indications and duration of PPI therapy have been summarized for easy assimilation. Individualized decision with regard to PPI use is illustrated by case vignettes; best approaches are provided. The significant increase in use of PPIs for ill-defined indications over the years, associated adverse outcomes with long-term use, and consequent increase in health care costs have drawn much attention. Adverse outcomes due to PPI therapy may be categorized as unrelated or related to gastric acid inhibition. Examples of outcomes unrelated to acid inhibition include allergic reactions, acute interstitial nephritis, chronic kidney disease, poor cardiovascular outcomes, dementia, and drug interactions; consequences of acid inhibition include gastrointestinal infections, pneumonia, nutrient deficiencies, fractures, spontaneous bacterial peritonitis, and small intestinal bacterial overgrowth. Provider awareness regarding best practice guidelines on PPI use and imparting pertinent education to patients may be the rational approach to safe and effective PPI therapy. In individuals in whom the drug is not indicated, efforts at deprescribing the PPI may be attempted following discussion with the patient. Approaches include stopping the drug, reducing the dose or using “on-demand” therapy after completing the course of treatment for the specific indication. Barriers to successful deprescribing exist. Follow-up is recommended for recurrence of manifestations; in the event of recurrence, the PPI may need to be re-instituted. PPIs are valuable, irreplaceable drugs in the prevention and treatment of certain disorders for specific durations of time. Evidence nevertheless suggests that excessive and inappropriately prolonged use of PPIs is associated with a broad range of adverse effects. Education of provider and patient, stewardship, and motivation are key to appropriate use of PPIs for the right indications. Key implications for practice are offered.
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