News Brief for November 2017

FDA Rejects Public Citizen Petition to Ban Oral Anti-fungal Drug

On September 1, the Food and Drug Administration (FDA) issued a final decision[1] on a petitiion[2] submitted by Public Citizen in 2015 that requested a ban on the oral form of the anti-fungal drug ketoconazole (available in generic only). The FDA denied the petition, opting to keep oral ketoconazole on the market despite the safety concerns raised in the petition. Two years after the approval of oral ketoconazole in 1981, a black-box warning was added to the label to inform health care providers and patients about the risk of fatal liver damage.

In July 2013, the FDA issued a safety communication restricting the approved uses of oral ketoconazole to rare, serious fungal infections and mandated that a medication guide be distributed with each prescription to inform patients of the drug’s severe risks of liver injury, adrenal gland disorders and potentially dangerous medication interactions. Unlike the FDA, the European Medicines Agency (EMA) in 2013 banned oral ketoconazole in Europe in response to the same evidence of harm. In addition, six months before the FDA’s July 2013 announcement restricting oral ketoconazole, a team of FDA scientists reached the same conclusion as the EMA: that oral ketoconazole should be removed from the market. The FDA denied Public Citizen’s petition, claiming that it is still uncertain how frequently oral ketoconazole causes liver damage and that the drug is necessary to treat the extremely rare, “systemic” fungal infections for which it is still approved. However, the FDA acknowledged in its denial letter that oral ketoconazole is still used almost exclusively for much more common fungal infections of the skin, a use for which even the FDA decided to withdraw approval for safety reasons in 2013.

The FDA did not even restrict the distribution of oral ketoconazole so that the drug could only be used for the extremely rare fungal infections for which it is still approved, no doubt because this action would cause all remaining manufacturers of the drug to cease production due to a lack of demand. Therefore, the FDA is effectively keeping a drug on the market solely for an unapproved (“off-label”) use that it has long since acknowledged poses too much of a danger to patients. Do not use oral ketoconazole for any use (note that this advice does not apply to topical ketoconazole products, such as shampoos and skin creams). If you are being treated with oral ketoconazole, see your doctor immediately to request that you be switched to another, safer anti-fungal drug.

References

[1] Food and Drug Administration. Letter denying Public Citizen petition to ban oral ketoconazole. September 1, 2017. https://www.citizen.org/sites/default/files/2241_final_fda_response_ketoconazole.pdf. Accessed September 7, 2017.

[2] Public Citizen. Petition to the FDA to ban all oral forms of the anti-fungal drug ketoconazole. February 24, 2015. https://www.citizen.org/sites/default/files/2241.pdf. Accessed September 7, 2017.