Appropriate Use and Stewardship of Proton-Pump Inhibitors

Dylan Ren, 2020 PharmD Candidate; Erin Gurney, 2020 PharmD Candidate; Jaime R. Hornecker, PharmD, BCPS, CDE, DPLA

US Pharmacist. 2019;44(12):25-31.

Abstract and Introduction

Abstract

Proton-pump inhibitors (PPIs) are commonly prescribed to patients or used for self-treatment for a variety of gastrointestinal complaints. While they are very effective, their use does not come without risk, especially when taken long-term. The pharmacist plays an important role in the judicious use of PPIs, particularly in educating patients on appropriate use to maximize their effectiveness and assisting with deprescribing PPIs, when possible.

Introduction

More than 25% of the population are affected by acid-related conditions, such as dyspepsia or gastroesophageal reflux disease (GERD).^[1] A high number of these individuals turn to and depend upon pharmacologic options for symptomatic relief and disease-state management. Since their introduction in 1989, proton-pump inhibitors (PPIs) have become one of the most commonly utilized medications worldwide, accounting for over $11 billion in expenditures annually.^[2,3] In the United States alone, it is estimated that over 100 million PPIs have been prescribed per year for the past 5 years.^[4] Currently, PPIs remain one of the top-selling drug classes in the country.^[5]

An estimated 113 million PPI prescriptions are filled globally every year.^[5] With their various indications, efficacy, and applicability for use in both ambulatory and inpatient settings, as well as with their availability as both OTC and prescription drugs, it is easy to see why PPIs have become a mainstay of pharmacotherapy for the management of acid-related disorders. Their versatility and profound use have ultimately led to their inclusion on the World Health Organization list of essential medications.^[6]

There are currently six FDA-approved PPIs available on the market. Given their clinical effectiveness and cost, they remain a top choice among patients and providers as a therapy option for a multitude of indications.^[7]

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Table 1. FDA-Approved Indications and Doses for PPI Therapy
FDA-Approved Indications	Omeprazole	Esomeprazole	Pantoprazole	Lansoprazole	Dexlansoprazole	Rabeprazole
Duodenal ulcer (treatment)	20 mg once a day	N/A	N/A	15 mg once a day for 4 weeks	N/A	20 mg once a day for 4 weeks
Duodenal ulcer (maintenance)	N/A	N/A	N/A	15 mg once a day	N/A	N/A
H pylori eradication (duodenal ulcer, reduce risk of recurrence)	Triple therapy: 20 mg bid for 10 days Dual therapy: 40 mg once a day for 14 days	Triple therapy: 40 mg once a day for 10 days	N/A	Triple therapy: 30 mg bid for 10–14 days Dual therapy: 30 mg tid for 14 days	N/A	Triple therapy: 20 mg bid for 7 days
Erosive esophagitis (treatment)	20 mg once a day for 4–8 weeks	20 mg or 40 mg once a day for 4–8 weeks, longer course may be warranted	40 mg once a day for up to 8 weeks	30 mg once a day for up to 8 weeks	60 mg once a day for up to 8 weeks	N/A
Erosive esophagitis (maintenance)	20 mg once a day	20 mg once a day	40 mg once a day	15 mg once a day	30 mg once a day	N/A
GERD (healing of erosive or ulcerative)	N/A	N/A	N/A	N/A	N/A	20 mg once a day for 4–8 weeks
GERD (maintenance of healing for erosive or ulcerative)	N/A	N/A	N/A	N/A	N/A	20 mg once a day
GERD (nonerosive symptomatic)	20 mg once a day for up to 4 weeks	20 mg once a day for longer course may be warranted	N/A	15 mg once a day for up to 8 weeks	30 mg once a day for 4 weeks	20 mg once a for 4 weeks
Gastric ulcer (benign short-term treatment)	40 mg once a day for 4–8 weeks	N/A	N/A	30 mg once a day for up to 8 weeks	N/A	N/A
Gastric ulcer (NSAID-associated)	N/A	N/A	N/A	30 mg once a day for up to 8 weeks	N/A	N/A
Gastric ulcer (risk reduction of NSAID-associated)	N/A	20 mg or 40 mg once a day for up to 6 months	N/A	15 mg once a day for up to 12 weeks	N/A	N/A
Heartburn OTC treatment	20 mg once a day for 14 days, may repeat every 4 months	N/A	N/A	15 mg once a day for 14 days	N/A	N/A
Pathological hypersecretory conditions	60 mg once a day, may adjust to patient needs	N/A	40 mg bid, may increase up to 240 mg	60 mg once a day, may adjust to patient needs to patient needs	N/A	60 mg once a day, may adjust

GERD: gastroesophageal acid reflux disease; H pylori: Helicobactor pylori N/A: not applicable; NSAID: nonsteroidal antiinflammatory drug; PPI: proton-pump inhibitor. Source: Reference 24.

Table 2. PPI-Associated Adverse Events and Mechanisms
PPI-Associated Adverse Event	Potential or Believed Mechanism
Hypomagnesemia	Increased gastric pH alters Mg transport and absorption
Vitamin B₁₂ deficiency	Increased gastric pH alters absorption, potential for microbial overgrowth that utilizes cobalamin
Clostridium difficile infection	Alteration of gut microbiome
Community-acquired pneumonia	Alteration of gut microbiome
Bone fracture	Reduction in calcium absorption due to increased gastric pH
Myocardial infarction	Unknown, believed to be related to impairment of endothelial nitric oxide synthase
Clopidogrel interaction and increased cardiovascular risk	Drug interaction
Dementia	Increased production and degradation of amyloid and binding to tau. Decreased availability of other nutrients
Acute interstitial nephritis	Cell- and humoral-mediated drug hypersensitivity