FDA Adds New Warning to Multaq Label

On Monday, the Food and Drug Administration (FDA) added a new safety warning to the label of heart rhythm drug Multaq (dronedarone) after studies showed that it doubled the risk of heart-related complications in a subset of patients; the drug also led to higher overall rates of heart attack, stroke, and death.

The new label will appear on Multaq’s packaging and was created with the aid of the drug’s manufacturer, Sanofi, which conducted the studies in question. In the studies, death only occurred when Multaq was used off-label to treat permanent atrial fibrillation; the drug is only approved to treat short-term atrial fibrillation and atrial flutter, a related condition.

The addition of the new warning label is just the latest in a series of setbacks for Multaq, which was highly anticipated when it received FDA approval in 2009 as the first new atrial flutter and atrial fibrillation drug in a decade. Multaq already bears a warning stating that it should not be used by patients with recent acute heart failure due to the possibility of serious complications, including death.

European Union health officials previously limited Multaq’s use based on the same safety information. In September, the European Medicines Agency advised doctors to use Multaq only after other treatments for atrial fibrillation had been tried

This most recent Sanofi study was ended for safety reasons. It included 3,236 patients with permanent atrial fibrillation over the age of 65. In all, 25 patients in the Multaq group died, compared with 13 in the placebo group, yielding a hazard ratio of 2.29.

The new label urges doctors not to prescribe the drug for permanent atrial fibrillation. Further, it directs physicians to assess patients’ heart rhythm at least once every three months and discontinue use of Multaq in patients who appear to have permanent atrial fibrillation.

In the last two years, the FDA has approved two other drugs for atrial fibrillation: Xarelto (rivaroxaban) and Pradaxa (dabigatran). Both are intended to be alternatives to warfarin, a 60-year old drug that is frequently prescribed for atrial fibrillation, but poses serious dosing challenges.

The FDA initially rejected Sanofi’s request to approve Multaq in 2006 after a widely publicized study showed that patients taking Multaq were twice as likely to die as non-Multaq patients.

Sanofi countered by arguing that the patients involved had severe heart failure and that many patients in the study did not even have the irregular heart rhythm Multaq was designed to treat. Sanofi followed up with a second study on patients with atrial fibrillation but without severe heart failure. This study found that Multaq reduced hospitalization and death from heart-related issues by 24% and helped lead to the drug’s approval by the FDA.

The new warning notwithstanding, the FDA reported on Monday that Multaq remains a valuable drug when used properly. The Multaq website has been updated with new safety information and a downloadable medication guide that explains the risks and new warnings issued by the FDA to patients.