Ketoconazole-Anti Fungal Medication Should Not Be Distributed

A consumer advocacy group has asked the FDA to immediately withdraw oral formulations of a decades-old fungal medicine over concerns that serious liver damage outweighs “questionable” benefits. And to reinforce its assertion, the consumer group cites an internal FDA memo in which agency staffers two years ago wrote that they did not view the risks associated with ketoconazole as “tolerable.”

The medicine was approved in 1981 to treat various fungal infections and several generic versions are currently available, although the original brand-name medicine is no longer sold. In its petition to the FDA, however, Public Citizen notes the FDA required a so-called black box warning – the most serious safety alert – for the drug in 1983 due to potentially fatal liver damage.

By July 2013, growing concerns prompted the FDA to issue a safety notice that removed several approved uses from the product labeling because of the risk of liver injury, adrenal gland dysfunction and troubling interactions with other medicines. The agency allowed oral versions of the drug to remain available for five fungal infections in the event other treatments fail or are not tolerated.

On the same day, though, the European Medicines Agency recommended all oral formulations be removed from the market over concerns about liver damage. The EMA review committee “could not identify a fungal infection where the level of hepatotoxicity of the drug could be balanced by an adequately substantiated benefit,” according to its report.

What was not previously known is that in January 2013, 14 staffers in the FDA Office of Surveillance and Epidemiology wrote a memo that the “overall benefit-risk assessment… is negative in the context of all of the drug’s labeled indications.” The 48-page review was undertaken after French regulators in 2011 suspended marketing authorization for the tablets due to safety concerns.

“The FDA’s own experts concluded that ketoconazole was too dangerous to remain on the market for any of its approved uses, yet the agency continues to allow hundreds of thousands of prescription for the medication to be filled each year,” says Sammy Almashat of Public Citizen in a statement. The consumer group says 462,000 prescriptions were written in 2014, citing IMS Health data.

An FDA spokeswoman would only say that the agency “will review the petition and respond directly to the petitioner.” We asked the three generic drug makers that sell ketoconazole in the U.S. – Teva Pharmaceuticals, Mylan Laboratories and Taro Pharmaceuticals – for comment, but no one has responded.