The FDA is taking several actions related to Nizoral (ketoconazole) oral tablets, including limiting the drug’s use, warning that it can cause severe liver injuries and adrenal gland problems and advising that it can lead to harmful drug interactions with other medications.
New label changes have been approved by the FDA and a new Medication Guide added to address these safety issues. As a result, Nizoral oral tablets should not be considered a first-line treatment for any fungal infection. 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.
Topical formulations of Nizoral have not been likewise associated with liver damage, adrenal problems, or drug interactions. These formulations include creams, shampoos, foams, and gels applied to the skin.
a) Liver Injury (Hepatotoxicity):
Nizoral tablets can cause liver injury, which may potentially result in liver transplantation or death. The FDA has revised the Boxed Warning, adding a strong recommendation against use in patients with liver disease, as well as, including new recommendations for assessing and monitoring patients for liver toxicity.
Serious liver damage has occurred in patients receiving high doses of Nizoral for short periods of time as well as those receiving low doses for long periods. Some of these patients had no obvious risk factors for liver disease. The liver injury is at times reversible upon stopping the drug, though that’s not always the case.
b) Adrenal Gland Problems (Adrenal Insufficiency):
Nizoral tablets may cause adrenal insufficiency by decreasing the body’s production of hormones known as corticosteroids. Corticosteroids are produced by the adrenal glands, which are small glands located on top of each kidney. Corticosteroids affect the body’s balance of water, salts and minerals (electrolytes).
Healthcare professionals should monitor adrenal function in patients taking Nizoral tablets who have existing adrenal problems, or in patients who are under prolonged periods of stress such as those who have had a recent major surgery or who are under intensive care in the hospital.
c) Drug Interactions:
Nizoral tablets show various interactions with other drugs a patient is taking and can result in serious and potentially life-threatening outcomes, such as heart rhythm problems. All medications that a patient is currently taking should be assessed for possible interactions with Nizoral tablets.
In summary, the drug label for Nizoral tablets has been updated to include the following information:
- Limiting the use of Nizoral tablet by removing indication in which the risk outweighs the benefits. The use of ketoconazole tablets in Candida and dermatophyte infections is no longer indicated. Nizoral tablets should be use only when other antifungal drugs are not available or tolerated by the patient.
- Nizoral tablets are indicated only for the treatment of the following fungal infections: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, andparacoccidiodomycosis in patients in whom other treatments have failed or who are intolerant to other therapies.
- Nizoral tablets are not indicated for the treatment of fungal infections of the skin or nails.
- A new contraindication that Nizoral tablets should not be used in patients with acute or chronic liver disease.
- Updated information on the risk of liver injury (hepatotoxicity), with new assessment and monitoring recommendations.
- Updated information on drug interactions.
- A warning regarding adrenal insufficiency with recommendations for monitoring populations at risk.
FDA will continue to evaluate the safety of Nizoral tablets and will communicate with the public again if additional information becomes available.
Nizoral and other ketoconazole-containing oral preparations have been unavailable on the Egyptian markets for over two years, and are only available in topical formulations.