The oral formulations of the antifungal medication ketoconazole should be removed from the market immediately, Public Citizen said this week in a petition to the Food and Drug Administration (FDA).
Ketoconazole was approved in 1981 to treat fungal infections; however, over the past 3 decades, evidence has mounted about the risks of the medication. In 1983, a black box warning was added to the label about fatal liver damage. In July 2013, FDA issued a safety communication restricting the approved uses of ketoconazole to rare, serious fungal infections and mandated that a medication guide be distributed with each prescription to inform patients of ketoconazole’s severe risks of liver injury, adrenal gland disorders and potentially dangerous medication interactions.
The same day as FDA’s announcement keeping ketoconazole on the US market, a committee of the European Medicines Agency recommended that all forms of ketoconazole be removed from the European market because the agency had concluded that the risks outweighed its limited benefits for any fungal infection., according to Public Citizen.
Using data relied on by the Office of Surveillance and Epidemiology (OSE) scientists in their analyses, Public Citizen conservatively estimated that approximately 600 cases of liver injury requiring hospitalization or a referral to a liver specialist may have resulted from the 462,000 prescriptions for ketoconazole used in the United States in 2014.
“Any drug with as dangerous of a side-effect profile – and limited/questionable benefits – as ketoconazole should be flagged by all involved in the healthcare system, especially officials such as formulary managers,” Sammy Almashat, MD, MPH, researcher with Public Citizen’s Health Research Group, told FormularyWatch. “For every fungal infection for which ketoconazole is still approved, there are multiple other treatments, including itraconazole and fluconazole that, in the words of FDA’s OSE reviewers demonstrate ‘comparable-to-enhanced efficacy and better safety profiles’ than ketoconazole. In other words, there is no remaining need for ketoconazole for any patient with a fungal infection.”
Public Citizen learned – after obtaining an unreleased, internal agency memo – that 6 months before the FDA’s July, 2013. announcement restricting ketoconazole, a team of FDA scientists at the OSE reached the same conclusion as the EMA: That ketoconazole should be removed from the market.
The OSE team was “unable to view the risk of serious potentially life-threatening [liver] injury as tolerable for the potential benefit of ketoconazole treatment” for any use. Importantly, the OSE scientists noted that, for all of ketoconazole’s remaining FDA-approved uses, multiple treatments exist that are safer and equally or more effective.
“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 prescriptions for the medication to be filled each year, likely resulting in hundreds of preventable cases of serious liver damage,” Almashat said. “FDA needs to listen to its own scientists and follow the EMA’s example in banning ketoconazole as an antifungal treatment.”