Long-term Consequences of Chronic Proton Pump Inhibitor Use

LeAnn W. O'Neill, PharmD; Benjamin L. Culpepper, PharmD; John A. Galdo, PharmD, BCPS


US Pharmacist. 2013;38(12):38-42. 

In This Article

Abstract and Introduction


Proton pump inhibitors (PPIs), available with or without a prescription, are commonly used for the treatment of acid-related disorders. Despite their ease of availability and common use, PPIs can have severe side effects. The long-term consequences of chronic PPI use include the potential increased risk of hypocalcemia, hypomagnesemia, Clostridium difficile infections, and pneumonia. Community pharmacists are poised to provide evidence-based recommendations and educate patients about the benefits and risks associated with chronic PPI use.


Proton pump inhibitor (PPIs) have been on the market since the late 1980s and have replaced the histamine2 receptor-antagonists (H2RAs) as the most potent class of drugs for the treatment of acid-related diseases.[1] Anti-ulcer medications (therapeutic areas are based on proprietary IMS Health definitions) were the ninth largest class based on prescription volume in the United States in 2012 and the 11th in sales.[2,3]

Medications in the PPI class are widely available with or without a prescription. Currently, the U.S. market contains six PPIs, two of which are also available as OTC products (Table 1).[4–9] In the early 2000s, the FDA announced the availability of omeprazole (Prilosec OTC) as the first OTC PPI.[10] It was soon followed by the approval of OTC lansoprazole (Prevacid 24HR).[11]

PPIs are used for the treatment of many gastric conditions including peptic ulcer disease, eradication of Helicobacter pylori infections, treatment and prevention of nonsteroidal anti-inflammatory drug (NSAID) gastroduodenal ulcer, Zollinger-Ellison syndrome, and gastroesophageal reflux disease (GERD).[1] Generally, these medications are prescribed because of the low incidence of side effects and superior efficacy compared to other drugs used to treat the same conditions.[1]

Long-term use of any medication raises safety concerns, especially if that product is available OTC. The American Gastroenterological Association (AGA) released guidelines on the management of GERD in 2008 that recommended against routine monitoring for PPIs due to insufficient evidence.[12] However, since then studies have continued to show long-term consequences from chronic PPI use including malabsorption consequences and infections. Subsequently, in March 2013, the American College of Gastroenterology (ACG) released guidelines for the diagnosis and treatment of GERD.[13] These guidelines do provide some insight into monitoring for long-term consequences of chronic PPI use. This article is a review of the recent literature and guideline recommendations regarding the possible long-term consequences of chronic PPI pharmacotherapy and opportunities to prevent these complications.

In animal studies, PPIs raised concerns about a potential for hypergastrinemia, but human studies failed to show an association.[1] Therefore, long-term consequences of chronic PPI use can be grouped into two main categories, malabsorption and infections.[1] Malabsorption secondary to PPI use affects calcium and magnesium, and the literature specifies two infections most often associated with PPI use, Clostridium difficile and pneumonia. Unfortunately, a definition in the literature for "long-term" is lacking; neither the AGA guidelines nor the ACG guidelines define what is considered long-term. For the rest of this article, the authors use long-term to designate therapy greater than 14 days, the maximum therapy for the OTC products.[10,11]