Proton pump inhibitors: Understanding the associated risks and benefits of long-term use

Abstract

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Proton pump inhibitors (PPIs) are widely prescribed medications. Various adverse clinical effects of PPIs have been reported in the literature, particularly over the past decade. The purpose of this article is to review published data primarily describing adverse effects associated with PPI use and to help clinicians determine which patients may still benefit from therapy despite safety concerns. Summary Associations between PPIs and the following have been described: bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, and coronavirus disease 2019 and respiratory infections. For inclusion in this review, studies must have evaluated potential adverse events associated with PPIs as a primary or secondary objective. Increased risks of bone fracture, acute and chronic kidney disease, gastrointestinal infections, and magnesium deficiency were consistently reported, albeit mostly in studies involving low-quality data (case-control and/or observational studies) and subject to bias. In the only pertinent randomized controlled trial to date, chronic pantoprazole use was associated with a greater risk of enteric infections relative to placebo use; there was no significant between-group difference in any other adverse event evaluated. PPIs continue to be recommended by the American College of Gastroenterology as a first-line treatment for management of gastroesophageal reflux disease and in the acute period following upper gastrointestinal and ulcer bleeding. Conclusion Higher-quality data is needed to better understand PPI-associated risks of the adverse effects listed above. Until then, clinicians may consider greater vigilance with PPI use; however, the data does not demonstrate a need for wide adoption of de-escalation strategies solely out of safety concerns.

Medication misuse and overuse in community‐dwelling persons with dementia

“…Third, high rates of medications frequently prescribed for symptom management, such as PPIs, NSAIDs, and antihistamines/antiemetics, can also be problematic among PWD. PPIs are frequently prescribed for long‐term use without a compelling indication, contributing to increased medication burden, drug–drug interactions, vitamin deficiencies, and possibly fractures/infections 38 . Many antihistamines and anticholinergic antiemetics frequently prescribed in our cohort (e.g., meclizine and promethazine), are not recommended given adverse effects, lack of significant benefit, and/or presence of safer alternatives.…”

Potassium-Competitive Acid Blockers for the Treatment of Gastroesophageal Reflux Disease

“…Although PPIs have a favorable safety profile and have been used for decades, their long-term use has been associated with possible adverse effects (AEs) including Clostridioides difficile infection, community-acquired pneumonia, bone fractures, hypomagnesemia, chronic kidney disease, vitamin B 12 deficiency, an increased risk of acquisition of Covid-19, and dementia. [58][59][60] However, for virtually all of these suspected adverse consequences, supporting evidence is weak and inadequate to establish causality. 61 In the only RCT to report prospective safety data, 3 years of daily PPI use was not associated with higher rates of AEs than placebo except for a small but statistically significant increase in the risk of bacterial enteritis.…”

Emerging factors affecting peri‐implant bone metabolism

“…336 Several adverse clinical effects related to PPIs have been reported in the literature, especially during the past decade. 337 Chronic use of this medication has been associated with an increased risk of bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, 337,338 and gastric cancer 336 among others. A recent review only found statistically significant differences between PPIs and the increased appearance of gastrointestinal infections, highlighting the need for more quality research in the field.…”

“…In the meantime, clinicians should consider exercising greater vigilance with PPI use. 337 Above all, the chronic use of PPIs may, because of acid suppression, decrease the absorption of vitamins, and nutrients, and this chronic situation can lead to states of vitamin B12, iron, calcium, and magnesium deficiencies and finally to a negative calcium balance, bone loss, and osteoporosis. 312 The association between PPIs and increased fracture risk is based on some potential mechanisms, such as hypochlorhydriaassociated malabsorption of calcium or vitamin B12, gastrin-induced parathyroid hyperplasia, and osteoclastic vacuolar proton pump inhibition.…”

“…Several adverse clinical effects related to PPIs have been reported in the literature, especially during the past decade 337 . Chronic use of this medication has been associated with an increased risk of bone fracture, acute and chronic kidney disease, gastrointestinal infections, deficiencies in vitamin B12 and magnesium, 337,338 and gastric cancer 336 among others.…”