August 7, 2013
FDA Severely Restricts Use of Nizoral Oral Tablets for
Fungal Infections

Washington, D.C.—Pharmacists should consider raising a red flag if ketoconazole oral tablets are prescribed as a first-line treatment for any fungal infections.

The FDA has severely limited use of the drug, marketed as Nizoral by Janssen Pharmaceuticals, while warning that it can cause severe liver injuries and adrenal gland problems, as well as harmfully interact with other medications. Drug labels are being changed to reflect the new concerns, and the FDA is requiring a new Medication Guide in light of the safety issues. The Boxed Warning also has been revised to say that use of Nizoral is contraindicated in patients with liver disease.

“Nizoral should be used for the treatment of certain fungal infections, known as endemic mycoses, only when alternative antifungal therapies are not available or tolerated,” according to the FDA.

A new safety alert reports that Nizoral tablets can cause liver injury, which may potentially result in liver transplantation or death; as part of the Boxed Warning revision, FDA is making new recommendations for assessing and monitoring patients for liver toxicity. The agency also is warning that Nizoral tablets may cause adrenal insufficiency by decreasing corticosteroid production.

Because serious and potentially life-threatening outcomes, such as heart rhythm disruption can occur, the FDA advises that, when Nizoral tablets must be used, all medications currently used by patients be assessed for possible interactions. Coadministration of ketoconazole is contraindicated with dofetilide, quinidine, pimozide, and cisapride because elevated plasma concentration can occur and cause prolonged QT intervals, sometimes resulting in life-threatening ventricular dysrhythmias such as torsades de pointes.

The drug label changes include the following:

• That ketoconazole tablets should only be used when other antifungal drugs are unavailable or not tolerated by patients;
• That use of the therapy in Candida and dermatophyte infections is no longer indicated;
• That use of the drug is limited only to treatment of blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis in patients in whom other treatments have failed or who are intolerant of other therapies;
• That Nizoral tablets should not be used for the treatment of fungal infections of the skin or nails.
• That the medication is contraindicated in patients with acute or chronic liver disease;
• Updated information is provided on the risk of liver injury, or hepatotoxicity, with new assessment and monitoring recommendations;
• Updated information is provided on drug interactions;
• A warning about adrenal insufficiency and recommendations for monitoring patients who might be at risk has been added.

The FDA’s action follows the suspension throughout the European Union of oral ketoconazole-containing medicines used to treat infections caused by dermatophytes and yeasts. That was based on a negative risk-benefit assessment and suspension recommendation by the Committee for Medicinal Products for Human Use of the European Medicines Agency.

Topical formulations of Nizoral have not been associated with liver damage, adrenal problems, or drug interactions and are not included in the safety alert. Creams, shampoos, foams, and gels containing ketoconazole are applied to the skin, unlike the Nizoral tablets, which are taken by mouth.

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