FDA Limits Usage of Oral Ketoconazole Due to Potentially Fatal Liver Damage
The U.S. Food and Drug Administration (FDA) announced today that oral ketoconazole should not be used as first-line treatment for any fungal infection and should only be used for the treatment of endemic mycoses when alternative antifungal therapies are not available or tolerated. The use of ketoconazole tablets in Candida and dermatophyte infections is no longer indicated.
This is the result of a comprehensive risk-benefit assessment of oral ketoconazole that found that the drug can cause severe or fatal liver damage, adrenal insufficiency, and may lead to harmful drug interactions with other medications. The FDA has approved label changes and added a new Medication Guide to address these safety issues. The topical formulations of ketoconazole have not been associated with liver damage, adrenal problems, or drug interactions.
The FDA decision came on the heels of an announcement from the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) recommending suspension of all oral ketoconazole–containing medicines in the European Union after a negative risk-benefit assessment for these drugs to treat infections caused by dermatophytes and yeasts.
Hepatotoxicity
The FDA has revised the Boxed Warning for oral ketoconazole, added a contraindication in patients with acute or chronic liver disease, and included new recommendations for assessing and monitoring patients for liver toxicity. Oral ketoconazole can cause liver injury, which may potentially result in liver transplantation or death.
Serious liver damage has occurred in patients—some of whom had no obvious risk factors for liver disease—receiving high doses of oral ketoconazole for short periods of time as well as those receiving low doses for long periods.
Adrenal Insufficiency
Ketoconazole tablets may cause adrenal insufficiency by decreasing the body’s production of corticosteroids. Health-care professionals should monitor adrenal function in patients taking oral ketoconazole 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.
Drug Interactions
Oral ketoconazole may interact with other drugs a patient is taking and can result in serious and potentially life-threatening outcomes, such as heart rhythm problems. Health-care professionals should assess all medications that a patient is currently taking for possible interactions with ketoconazole.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
