What is an exception regarding Proton Pump Inhibitors (PPIs)?

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Last updated: July 6, 2025View editorial policy

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From the Guidelines

PPIs are not entirely safe for long-term use in all patients, but they are generally considered safe, especially when the benefits outweigh the risks, such as in patients with a history of severe erosive esophagitis or GERD-related complications 1. When considering the safety and efficacy of PPIs, it's essential to weigh the benefits and harms, particularly in patients with a history of severe erosive esophagitis or GERD-related complications.

  • PPIs have been shown to be effective in healing erosive esophagitis and preventing the development and recurrence of complications of GERD in long-term users 1.
  • However, de-prescribing can be considered in patients without a history of severe erosive esophagitis or GERD-related complications, but PPI use should be quickly re-initiated in those who develop symptoms or signs suggestive of the emergence of complicated GERD 1.
  • Optimization of PPI includes ensuring adequate timing of dose, considering escalation to double dose, and/or switching to a different PPI, and when symptoms are adequately controlled, acid suppression should be weaned down to the lowest effective dose 1.
  • Exceptions to weaning acid suppression include patients with erosive esophagitis (Los Angeles B or greater), biopsy-proven Barrett’s esophagus, and/or peptic stricture, who will require at least single-dose, long-term PPI therapy 1. The correct answer is A, as PPIs are not entirely safe for long-term use in all patients, but the safety concerns should be balanced against the benefits of treatment, particularly in patients with severe disease 1.

From the Research

Exceptions Regarding Proton Pump Inhibitors (PPIs)

  • Not safe for long-term use: PPIs can lead to increased gastric pH, hypochlorhydria, and in some cases achlorhydria, resulting in significant vitamin and mineral deficiencies 2.
  • Potential risk of congenital malformations: Long-term use of PPIs by pregnant patients may impose a potential risk of congenital malformations, although omeprazole is considered a safe choice for severe conditions of gastroesophageal reflux disease 2.
  • Increased risk of bone fractures: Long-term use of PPIs has been associated with an increased risk of bone fractures, including hip, spine, and wrist fractures 3, 4, 5, 6.
  • Acid-blocking action: PPIs have a stronger acid-blocking action compared to histamines, which can lead to hypochlorhydria and increased risk of enteric, respiratory, and urinary tract infections 2.
  • Concomitant use with antiplatelet drugs: The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose patients to major adverse cardiac events 2.
  • Dosage and timing: It is recommended to take PPIs 30-60 minutes before food to ensure optimal absorption and effectiveness.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Proton Pump Inhibitors and Bone Health: An Update Narrative Review.

International journal of molecular sciences, 2022

Research

The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study.

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2013

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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