EMA suspends use of oral ketoconazole because of liver injury risk

The European Medicines Agency’s Committee on Medicinal Products for Human Use (CHMP) has recommended that the marketing authorizations of oral ketoconazole-containing medicines should be suspended throughout the European Union. The CHMP concluded that the risk of liver injury is greater than the benefits in treating fungal infections.

The EU-wide review of oral ketoconazole was triggered by the suspension of the medicine in France. The French medicine agency, the National Agency for the Safety of Medicine and Health Products (ANSM), concluded that the benefit-risk balance of oral ketoconazole was negative because of a high level of liver injury associated with the medicine and in view of the currently available alternative treatments, which are deemed to be safer.

The CHMP concluded that, although liver injury such as hepatitis is a known side effect of antifungal medicines, the incidence and the seriousness of liver injury with oral ketoconazole were higher than with other antifungals. The CHMP was concerned that reports of liver injury occurred early after starting treatment with recommended doses, and it was not possible to identify measures to adequately reduce this risk. It also concluded that the clinical benefit of oral ketoconazole is uncertain as data on its effectiveness are limited and do not meet current standards, and alternative treatments are available.