FDA: Severe liver injury associated with dronedarone use

Severe liver injury, including 2 cases of acute liver failure leading to liver transplant in patients treated with the medication, has been associated with the use of dronedarone (Multaq), according to an FDA Drug Safety Communication announcement.

Dronedarone is an antiarrhythmic drug indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL) with a recent episode of AF/AFL and associated cardiovascular risk factors (age >70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction

Since dronedarone’s approval in July 2009 through October 2010, about 492,000 dronedarone prescriptions were dispensed and around 147,000 patients filled dronedarone prescriptions at outpatient retail pharmacies in the United States. Additional usage can occur in the hospital setting.

“For some time during its developmental stages, the cardiology community had hoped that dronedarone would be an ideal alternative for its predecessor, amiodarone,” said Formulary Clinical Editor David Calabrese, RPh, MHP.

“When dronedarone entered the market, it appeared to offer a more favorable toxicity profile than amiodarone, but the clinical data also suggested that it may not be as effective in treating atrial fibrillation and was far more expensive,” said Calabrese, chief clinical officer, Med Metrics Health Partners, Worcester, Mass. “Now, with the emergence of this new potential hepatotoxicity risk, along with previously-raised concerns of pro-arrhythmic effects and exacerbation of heart failure in high-risk patients, the purported safety advantages of this entity are also being called into question.”

Dronedarone was approved with a Risk Evaluation and Mitigation Strategy (REMS) with a goal of preventing its use in patients with severe heart failure or who have recently been in the hospital for heart failure. In a study of patients with these conditions, patients given dronedarone had a greater than 2-fold increase in risk of death.

FDA has received several case reports of hepatocellular liver injury and hepatic failure in patients treated with dronedarone, including 2 post-marketing reports of acute hepatic failure requiring transplantation. Because these reactions are reported voluntarily from a treatment population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Information about the potential risk of liver injury from dronedarone is being added to the Warnings and Precautions and Adverse Reactions sections of the dronedarone labels.