The U.S. Food and Drug Administration (FDA) is informing the public that the use of stomach acid drugs known as proton pump inhibitors (PPIs) may be associated with an increased risk of Clostridium difficile–associated diarrhea (CDAD).
A diagnosis of CDAD should be considered for patients taking PPIs who develop diarrhea that does not improve.
Patients should immediately contact their healthcare professional and seek care if they take PPIs and develop diarrhea that does not improve.
The FDA is working with manufacturers to include information about the increased risk of CDAD with use of PPIs in the drug labels.
FDA is also reviewing the risk of CDAD in users of histamine H2 receptor blockers. H2 receptor blockers are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and heartburn. H2 receptor blockers are marketed under various brand and generic drug names as prescription and OTC products.
Today's communication is in keeping with FDA's commitment to inform the public about the Agency's ongoing safety review of drugs. FDA will communicate any new information on PPIs or H2 receptor blockers and the risk of CDAD when it becomes available.
Facts about Proton Pump Inhibitor (PPI) Drugs
- Marketed under various brand and generic drug names as prescription and over-the-counter (OTC) products.
AcipHex" data-scaytid="35">AcipHex (rabeprazole sodium)
Dexilant" data-scaytid="39">Dexilant (dexlansoprazole" data-scaytid="41">dexlansoprazole)
Nexium (esomeprazole magnesium)
Omeprazole" data-scaytid="47">Omeprazole (omeprazole) Over-the-Counter (OTC)
Prevacid (lansoprazole) and OTC Prevacid 24hr
Prilosec" data-scaytid="61">Prilosec (omeprazole) and OTC
Protonix (pantoprazole sodium)
Vimovo (esomeprazole magnesium and naproxen" data-scaytid="73">naproxen)
Zegerid" data-scaytid="75">Zegerid (omeprazole and Sodium bicarbonate) and OTC
- Work by reducing the amount of acid in the stomach.
- Prescription PPIs are used to treat conditions such as gastroesophageal reflux disease (GERD), stomach and small intestine ulcers, and inflammation of the esophagus.
- Over-the-counter PPIs are used to treat frequent heartburn.
Additional Information for Patients and OTC Consumers:
- Seek immediate care if you use PPIs and develop diarrhea that does not improve. This may be a sign of Clostridium difficile–associated diarrhea (CDAD).
- Your healthcare professional may order laboratory tests to check if you have CDAD.
- Do not stop taking your prescription PPI drug without talking to your healthcare professional.
- Discuss any questions or concerns about your PPI drug with your healthcare professional.
- If you take an OTC PPI drug, follow the directions on the package carefully.
- Report any side effects you experience to the FDA MedWatch program.
FDA has reviewed reports from the FDA's Adverse Event Reporting System (AERS) and the medical literature for cases of Clostridium difficile-associated diarrhea (CDAD) in patients undergoing treatment with PPIs. Many of the adverse event reports involved patients who were elderly, had chronic and/or concomitant underlying medical conditions, or were taking broad spectrum antibiotics that could have predisposed them to developing CDAD. Although these factors could have increased their risk of CDAD, the role of PPI use cannot be definitively ruled out in these reviewed reports. Patients who have one or more of these risk factors may have serious outcomes from CDAD with concomitant PPI use.
FDA also reviewed a total of 28 observational studies described in 26 publications. Twenty-three of the studies showed a higher risk of C. difficile infection or disease, including CDAD, associated with PPI exposure compared to no PPI exposure.2-27 Although the strength of the association varied widely from study to study, most studies found that the risk of C. difficile infection or disease, including CDAD, ranged from 1.4 to 2.75 times higher among patients with PPI exposure compared to those without PPI exposure. In the five studies that provided information on clinical outcomes, colectomies, and rarely deaths, were reported in some patients.
The published studies varied in their ability to assess the association between C. difficile infection or CDAD and prior PPI use. There were limited data on the relationship between the risk of C. difficile infection or CDAD and PPI dose and duration of use. There also was little information on the use of OTC PPIs in community settings in these studies. Nevertheless, the weight of evidence suggests a positive association between the use of PPIs and C. difficile infection and disease, including CDAD.