The FDA ( Food and Drug Administration ) has completed a safety review of Multaq ( Dronedarone ). This review showed that Multaq increased the risk of serious cardiovascular events, including death, when used by patients in permanent atrial fibrillation. The review was based on data from two clinical trials, PALLAS and ATHENA.
FDA is providing new information and recommendations for the use of Multaq to manage the potential serious cardiovascular risks with the drug.
The Multaq drug label has been revised with the following changes and recommendations:
a) healthcare professionals should not prescribe Multaq to patients with atrial fibrillation who cannot or will not be converted into normal sinus rhythm ( permanent atrial fibrillation ), because Multaq doubles the rate of cardiovascular death, stroke, and heart failure in such patients ;
b) healthcare professionals should monitor cardiac rhythm by electrocardiogram ( ECG ) at least once every 3 months. If the patient is in atrial fibrillation, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted;
c) Multaq is indicated to reduce hospitalization for atrial fibrillation in patients in sinus rhythm with a history of non-permanent atrial fibrillation ( known as paroxysmal or persistent atrial fibrillation ) ;
d) patients prescribed Multaq should receive appropriate antithrombotic therapy.
The PALLAS ( Permanent Atrial FibriLLAtion Outcome Study Using Dronedarone on Top of Standard Therapy ) trial was a large outcome trial intended to evaluate the effectiveness of Multaq in patients with permanent atrial fibrillation. This clinical trial was terminated early because of a significantly higher number of cardiovascular events in the Multaq-treated group compared to the group of patients given a placebo.
Final results from PALLAS ( provided by the manufacturer ) showed the following: Multaq ( Dronedarone ) N=1619 vs Placebo N=1617: total deaths 25 vs 13, hazard ratio HR=1.94; death from arrhythmia or sudden death: 13 vs 4, HR=3.26; stroke: 23 vs 10, HR=2.32 ; hospitalization for heart failure: 43 vs 24, HR=1.81.
To determine whether the increased risks observed in the PALLAS study population apply to patients for whom the drug is indicated ( i.e., patients with non-permanent atrial fibrillation ), the FDA reassessed data from the ATHENA trial ( the clinical trial supporting Multaq's approval for non-permanent atrial fibrillation ), with special attention to arrhythmic death, stroke, and heart failure outcomes.
The ATHENA trial showed a reduction in the risk of hospitalizations for atrial fibrillation in patients with non-permanent atrial fibrillation who were randomized to receive Multaq. Patients administered Multaq in the ATHENA trial did not have an increased risk of cardiovascular death, stroke or heart failure.
The FDA believes that Multaq provides a benefit for patients with non-permanent atrial fibrillation and recommends that healthcare professionals who prescribe Multaq follow the recommendations in the revised Multaq drug label.
From approval in July 2009 through October 2011, a total of approximately 1.3 million Multaq prescriptions were dispensed and approximately 278,000 patients received Multaq prescriptions from U.S. outpatient retail pharmacies.
Source: FDA, 2011