The US FDA has issued a drug safety communication, notifying healthcare professionals and patients in the US about rare cases of severe liver injury reported in association with use of dronedarone (Multaq®) for atrial fibrillation. This includes two patients with acute liver failure that required transplantation, occurring at 4.5 and 6 months after the start of treatment.  In both cases, the explanted liver showed evidence of extensive hepatocellular necrosis.  Both patients were female and around the age of 70 years, and had normal liver function tests at the start of therapy.

Healthcare professionals in the US are given the following advice:

• Patients should be advised to contact a healthcare professional immediately if they experience signs and symptoms of hepatic injury or toxicity (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching) while taking dronedarone.

• Consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment. However, it is not known whether routine periodic monitoring of serum liver enzymes (ALT, AST, and alkaline phosphatase) and bilirubin in patients taking dronedarone will prevent the development of severe liver injury.

• If hepatic injury is suspected, dronedarone should be promptly discontinued and testing of serum liver enzymes and bilirubin should be performed. If hepatic injury is found, appropriate treatment should be initiated.

• Dronedarone should not be restarted in patients who experience hepatic injury without another explanation for the observed liver injury.

In the data summary (available at the link below), the FDA notes that it is not always possible to establish causality or reliably estimate the frequency of such a reaction, due to voluntarily reporting from a treatment population of an unknown size.   

The US prescribing information for dronedarone will be updated on the basis of this information and a warning about potential liver injury will be added to the drug's label.  A spokesperson for sanofi-aventis said the company is also working with other regulatory authorities, including the European Medicines Agency.