U.S. drug regulators announced on Monday, December 19, 2011 new restrictions for Multaq (dronedarone), a medication that treats atrial fibrillation. According to the Food & Drug Administration (FDA), Multaq should not be used to treat people with permanent atrial fibrillation, a condition in which the heart’s chambers pump out of sync.
They have added new safety warnings to the Sanofi drug Multaq after company studies linked the heart drug to higher rates of heart attack, stroke and death in a subset of patients.
Multaq was FDA approved in 2009 to treat people with temporary atrial fibrillation. According to a report from The Wall Street Journal, Multaq was expected to be l$1-billion-a-year seller because millions of people suffer from that disorder.
According to the New England Journal of Medicine, Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects.
The FDA began conducting a safety review of Multaq in January 2011. At that time, the agency updated the drug’s label to state that “liver injury, including acute liver failure requiring transplant, has been reported in patients treated with Multaq.” Then in July, the agency expanded the Multaq review to include heart side effects, after a study found that people who received Multaq for permanent atrial fibrillation faced ace a doubled risk of death, as well as a higher rate of heart attack and stroke. That study, known as the PALLAS (Permanent Atrial FibriLLAtion Outcome Study) clinical trial, was evaluating the use of Multaq in people over 65 with permanent atrial fibrillation. PALLAS was terminated over the summer after Multaq-treated patients experienced a higher-than expected frequency of adverse heart events.
According to a Drug Safety Communication issued, a total of 25 Multaq-treated patients died during PALLAS, versus 13 who were on a placebo. Fourteen Multaq patients died suddenly or experienced death from arrhythmia, versus only 4 in the placebo group. Twenty-three being treated with Multaq suffered stroke, while 43 were hospitalized with heart failure. In the placebo group, only 10 suffered a stroke, while 24 were hospitalized with heart failure.
As part of its safety review, the FDA also reassessed data from the ATHENA clinical trial, which was used to grant Multaq’s approval for temporary atrial fibrillation. In the safety communication, the agency said Multaq patients in that study did not have an increased risk of cardiovascular death, stroke or heart failure. As such, the FDA continues to believe that Multaq provides a benefit for patients with non-permanent atrial fibrillation.
The new label stresses that Multaq is only approved for the short-term form of the condition and a related ailment known as atrial flutter.
According to the latest safety communication, the FDA recommends that 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. They should also monitor heart (cardiac) rhythm by electrocardiogram (ECG) at least once every 3 months. And, if the patient is in atrial fibrillation, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted.
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).
Patients prescribed Multaq should receive appropriate antithrombotic therapy.
The new label is the latest safety setback for Multaq, which was once thought to be a potential blockbuster. Multaq already carries a warning that the drug should not be used by heart failure patients.