CardioExchange Archive

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended new restrictions on dronedarone (Multaq), Sanofi’s embattled and controversial antiarrhythmic drug. CHMP says that dronedarone should only be used for maintaining sinus rhythm in patients with paroxysmal or persistent AF after successful cardioversion. The drug should no longer be used in patients who still have AF, CHMP says.

Because dronedarone increases the risk for liver, lung, and cardiovascular adverse events, CHMP adds that it should be used only after alternative treatments have been considered. People already taking dronedarone should “have their treatment evaluated by their doctor at their next scheduled appointment.”

CHMP and the FDA began their reviews of dronedarone in January of this year after receiving reports of severe liver injury in people taking the drug. The review was broadened in July when the PALLAS trial of dronedarone for the treatment of permanent AF was terminated early due to a significant increase in cardiovascular events in the dronedarone arm of the trial.

In its review, CHMP concludes that dronedarone increases the risk for injury to the liver and the lungs and may increase the risk for cardiovascular side effects in some patients with nonpermanent AF. However, CHMP affirms that for some patients with nonpermanent AF, the drug “remains a useful treatment option” and that its benefits outweigh its risks for these patients.

CHMP also recommends that:

• Dronedarone should only be prescribed by a specialist after other antiarrhythmic agents have been considered.
• Dronedarone should not be used in patients with permanent AF, heart failure, or left ventricular systolic dysfunction.
• Doctors should consider discontinuation of dronedarone if AF recurs.
• Dronedarone must not be used in patients who have had previous liver or lung injury associated with treatment with amiodarone.
• Patients receiving dronedarone should have regular tests to monitor lung and liver function.

The FDA told CardioBrief that it is continuing its review of the safety of dronedarone and that it hopes “to soon update the public with more information.”

In an article about dronedarone in the Wall Street Journal, several cardiologists had harsh words about dronedarone. Sanjay Kaul said the drug is “not even safe in intermediate-risk patients,” and Steve Nissen said he thought the drug is “dangerous.” Electrophysiologist John Mandrola said the drug “just doesn’t work.” Sanofi’s CEO told the Journal that “the company has had ‘positive’ discussions with regulators.”