The MedWatch program, part of the Food and Drug Administration (FDA), has issued a notice that the use of proton pump inhibitors, which decrease the production of gastric acid, may increase the risk of developing Clostridium difficile-associated diarrhea. The notice is a result, in part, of a review of case reports submitted to the MedWatch reporting system. Many of the case reports involved older patients, patients with chronic or concurrent underlying medical conditions (or both), or patients who were taking broad-spectrum antibiotics. Any of these factors could have increased their risk of C. difficile-associated diarrhea, but the role of proton pump inhibitors couldn't be ruled out. The FDA also reviewed 28 observational studies on this possible connection and concluded that, despite limitations in those studies, the evidence suggests a positive association between the use of proton pump inhibitors and C. difficile infection and disease.

Over-the-counter and prescription formulations of proton pump inhibitors are available, and all may increase this risk. Drug labels will be revised to include this information. Patients should take the lowest effective dosage possible and for as short a time as possible to prevent C. difficile-associated diarrhea. Nurses should instruct patients receiving these medications to contact their health care provider and seek care if they develop watery diarrhea that doesn't improve or other symptoms of C. difficile infection, such as abdominal pain, fever, or anorexia. Patients taking over-the-counter proton pump inhibitors should be encouraged to take the drug only as stated on the label.

MedWatch has also issued a notice that an interaction may occur between boceprevir (Victrelis), a protease inhibitor used in the treatment of hepatitis C virus (HCV), and certain ritonavir (Norvir)-boosted protease inhibitors used in the treatment of HIV, including atazanavir (Reyataz), lopinavir (Kaletra), and darunavir (Prezista). The interaction of these two therapies can reduce the effectiveness of both. If a patient has been started on this combination, nurses should assess the patient's response to hepatitis C treatment and look for increases in HCV and HIV viral loads. Patients don't need to stop taking these drugs immediately and should do so only under the direction of the prescriber.

To report cases of these adverse effects, go to http://www.fda.gov/MedWatch/report.htm.