FDA, EMA Come Down Hard on Oral Ketoconazole

July 26, 2013

Clinicians should no longer prescribe ketoconazole (Nizoral, Janssen Pharmaceuticals) tablets as a first-line therapy for any fungal infection because of the risk for severe liver injury, adrenal insufficiency, and adverse drug interactions, the US Food and Drug Administration (FDA) announced today.

The restriction is one of numerous label changes that the FDA imposed on the oral version of the antifungal therapy. They do not apply to topical formulations of ketoconazole in creams, shampoos, foams, and gels.

The agency action coincides with today's recommendation by European Union (EU) drug regulators to withdraw ketoconazole tablets from EU national markets. The European Medicines Agency (EMA) stated in a news release that "the risk of liver injury is greater than the benefits in treating fungal infections."

In the United States, the FDA is withdrawing the indication of ketoconazole tablets completely for Candida and dermatophyte infections. Oral ketoconazole is now indicated only for certain life-threatening fungal infections, known as endemic mycoses, in patients who fail to respond to other treatments or who cannot tolerate them. The fungal infections in this family are:

The FDA instructs clinicians not to prescribe ketoconazole tablets for any patients with underlying liver disease. Anyone taking the drug should undergo weekly tests of alanine aminotransferase levels for the sake of recognizing potential liver injury as soon as possible.

More information about today's announcement is available on the FDA Web site.

To report problems with ketoconazole tablets, contact MedWatch, the FDA's safety information and adverse event reporting program, by telephone at 1-800-FDA-1088; by fax at 1-800-FDA-0178; online at https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm; with postage-paid FDA form 3500, available at https://www.fda.gov/MedWatch/getforms.htm; or by mail to MedWatch, 5600 Fishers Lane, Rockville, Maryland 20852-9787.


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