[Emergent adverse effects of proton pump inhibitors]

Abstract

Background: Recent literature reports of potential adverse effects (AEs) of proton pump inhibitors (PPIs), especially during long-term treatments.

Purpose: To present a literature review of major AEs: digestive infections, pneumonia, bone fracture, hypomagnesemia, interstitial nephritis, gastric cancer and neutropenia.

Data sources: The authors used Pubmed; articles in English or French, published between August 2006 and August 2011 were analyzed.

Study selection: Two reviewers analyzed the references of title and summary to retain mainly observational studies, controlled clinical trials, meta-analyzes, case reports.

Results: For digestive infections: observational studies have shown a link moderate to high (OR 1.4 to 8.3) with exposure to PPIs. For pneumonia: some case-control studies reported a modest significative risk (OR 1.2 to 1.6), some not. The risk appears dose dependent and greater in subjects at risk. For fractures: the majority of observational studies report a significative increase in low to moderate risk (OR 1.2 to 3.1), correlated with the dose and duration of treatment. For magnesium deficiency: rare but potentially severe, they are described in case reports. Interstitial nephritis are described in case reports and for different PPIs, suggesting a class effect. For the stomach neoplasm: if three observational studies show an increased cancer risk (OR 1.5 to 2, 3), confounding factors make the causal link uncertain. Neutropenia is reported in a clinical observation, a class effect is suggested.

Limitations: One can regret the absence of controlled clinical trials; indeed the observational studies have the interest to move closer to "real life", but often have methodological bias.

Conclusion: Although AEs PPIs do not call into question the usefulness of this drug class, they show the need to limit their prescribing to indications for which efficacy has been proven. Moreover, PPIs treatment must be regularly reassessed to avoid exposing patients to unnecessary risks.