Perils and Pitfalls of Long-term Effects of Proton Pump Inhibitors

Abstract

This review summarizes the literature regarding long-term adverse effects of proton pump inhibitors (PPIs). A PubMed search (1966 to February 2013) for English language studies was conducted using key terms PPI: omeprazole, esomeprazole, pantoprazole, lansoprazole, dexlansoprazole, rabeprazole, pneumonia, Clostridium difficile, osteoporosis, risk of fractures, thrombocytopenia, rhabdomyolysis, anemia, iron deficiency, hypomagnesemia, vitamin B₁₂ and nephritis. The risk of pneumonia was increased 27–39% in short-term use of PPIs in three meta-analyses. C. difficile infections were also associated with the use of PPIs (odds ratio: 2.15; 95% CI: 1.81–2.55; p < 0.00001). This effect appears to be dose related. The US FDA has recently issued a warning regarding fractures and the impaired magnesium absorption associated with the use of PPI. Thrombocytopenia, iron deficiency, vitamin B₁₂ deficiency, rhabdomyolysis and acute interstitial nephritis have also been reported with the use of PPIs. There is mounting evidence that PPIs are associated with serious adverse effects. Practitioners should be vigilant and counsel patients accordingly

Expert Commentary

There is widespread use of PPIs for a number of indications both in the inpatient and outpatient settings. While PPIs are generally considered safe and well tolerated, more serious adverse events have been reported. The risk of pneumonia was increased 27–39% in short-term use of PPIs in three meta-analyses. The use of PPIs is associated with CDI and appears to be dose related. Fractures and the impaired magnesium absorption associated with the use of PPIs have led the FDA to issue a warning regarding their use. Thrombocytopenia, iron deficiency, vitamin B₁₂ deficiency, rhabdomyolysis and AIN have also been reported with the use of PPIs.

Sheila M Wilhelm, Ryan G Rjater, Pramodini B Kale-Pradhan
DisclosuresExpert Rev Clin Pharmacol. 2013;6(4):443-451.