FDA to revise all PPI labels to warn about possible fracture risk

Labeling for all prescription and over-the-counter proton pump inhibitors will have to include wording about a possible increased risk of hip, wrist, and/or spine fractures with their use.

Key Points

FDA has announced that the warnings and precautions sections of labeling for all prescription and over-the-counter (OTC) proton pump inhibitors (PPIs) - including esomeprazole (Nexium, Vimovo), dexlansoprazole (Dexilant), omeprazole (Prilosec, Prilosec OTC, Zegerid, Zegerid OTC), lansoprazole (Prevacid, Prevacid 24HR), pantoprazole (Protonix) and rabeprazole (Aciphex) - will have to include wording about a possible increased risk of hip, wrist, and/or spine fractures with their use.

Specifically, FDA cites 7 observational studies published between 2006 and 2010 in their recent safety communication released on May 25, 2010. Of these 7 studies, all but one reported an increased risk of fractures of the hip, wrist and/or spine in patients using PPIs. Furthermore, 2 of the 7 studies suggested the fracture risk increased as the dose of PPI increased, and 2 reported a correlation between increased fracture risk and longer durations of PPI use. Overall, the increased risk of fractures seen with PPIs in these studies was primarily observed in older patients.

While FDA noted, "the exact mechanisms for an increased risk of fractures with proton pump inhibitor use are not known," investigators from cited studies hypothesized that the increased fracture risk is a result of calcium malabsorption secondary to acid suppression (an acidic environment in the gastrointestinal tract facilitates the release of ionized calcium from insoluble calcium salts).

Despite these uncertainties, FDA is suggesting that providers weigh the proven benefits of PPIs against these potential risks when deciding to use them. They are also recommending to consider whether a lower dose or shorter duration of PPI could be used.

SOURCES

FDA. Proton Pump Inhibitors (PPI): Class Labeling Change including Nexium, Dexilant, Prilosec, Zegerid, Prevacid, Protonix, Aciphex, Vimovo, Prilosec OTC, Zegerid OTC, and Prevacid 24HR. May 25, 2010. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213321.htm. Accessed June 1, 2010.

FDA. FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. May 25, 2010. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed June 1, 2010.

Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296:2947–2953.