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Ketoconazole (Nizoral) Drug Safety Communication - Potentially Fatal Liver Injury, Risk of Drug Interactions and Adrenal Gland Problems - UPDATE

May 19, 2016

FDA issued a safety announcement to warn against prescribing ketoconazole oral tablets for dermatologic or nail fungal infections. Labeling was changed in 2013 to include this warning, but the medication has continued to be prescribed for this use.

FDA approved label changes and added a new Medication Guide for ketoconazole (Nizoral) oral tablets in 2013. Ketoconazole labeling includes limited approved uses, updated information on drug interactions, and warnings associated with liver injury and adrenal gland issues. Ketoconazole oral tablets are only approved for certain endemic mycoses when other antifungal therapies cannot be used. Do not use ketoconazole tablets for any antifungal infections of the skin or nails. Of note, ketoconazole topical formulations including creams, shampoos, foams, and gels, have no association with liver injury, adrenal issues, or drug interactions.

Liver injury caused by the ketoconazole tablets may result in liver complications that may lead to transplantation or death. FDA updated the black box warning to include a contraindication for patients with liver disease and new monitoring parameters for liver function. Since the labeling update, there has been 1 reported patient death attributed to oral ketoconazole-induced liver failure. A warning was also added regarding adrenal insufficiency associated with ketoconazole. Ketoconazole can induce adrenal insufficiency by reducing the body’s natural production of corticosteroids. In addition, significant and deadly drug interactions can result from using ketoconazole tablets, including problems with heart rhythms.

Reserve ketoconazole tablets as last line treatment of certain life-threatening mycoses. If ketoconazole is initiated, conduct a baseline liver evaluation, weekly ALT serum levels, and adrenal function assessment as needed. Evaluate all concomitant medications for potential drug interactions prior to starting ketoconazole tablets.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program: http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadForms/default.htm

Updated
May 19, 2016; July 26, 2013; University of Utah, Drug Information Service. Copyright 2016, Drug Information Service, University of Utah, Salt Lake City, UT.