FDA Alert : Multaq (Dronedarone) Increased Risk Of Death / Cardiovascular Problems

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Main Category: Cardiovascular / Cardiology
Also Included In: Regulatory Affairs / Drug Approvals
Article Date: 19 Dec 2011 - 16:00 PST

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The drug Multaq, from Sanofi-Aventis, is used to treat cardiac arrhythmias, however the FDA has issued a warning today stating that in further trials it has shown a serious risk of cardiovascular problems, including death.

More specifically the FDA states that Multaq must now carry the warning :

"Healthcare professionals should not prescribe Multaq to patients with Permanent Atrial Fibrillation who cannot or will not be converted into normal sinus rhythm (permanent AF), because Multaq doubles the rate of cardiovascular death, stroke, and heart failure in such patients."

The FDA review and warning was based on data gathered during the PALLAS and ATHENA trials. 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 AF. 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.

Multqa was originally approved by the FDA in July 2009, as an alternative to amiodarone, for the treatment of atrial fibrillation and atrial flutter in patients whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment to maintain normal rhythm. However, the FDA did not approve dronedarone for reducing deaths. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe Coronary Heart Failure.

Chemically, dronedarone is a benzofuran derivative related to amiodarone, a popular antiarrhythmic, the use of which is limited by toxicity due its high iodine content (pulmonary fibrosis, thyroid disease) as well as by liver disease.

Other known issues with the drug included not using it in pregnant or nursing women, where heart rate is below 50bpm, where QT interval is 500msec or greater (i.e. from beginning of the strongest part of the beat, to the end of the entire cycle.) or where PR interval (i.e. from the beginning of the strongest point of the beat to the strongest point of the beat) exceeds 280msec.

In addition the FDA stated that :

• Healthcare professionals should monitor heart (cardiac) rhythm by electrocardiogram (ECG) at least once every 3 months. If the patient is in AF, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted.
• Multaq is indicated to reduce hospitalization for AF in patients in sinus rhythm with a history of non-permanent AF (known as paroxysmal or persistent AF)
• Patients prescribed Multaq should receive appropriate antithrombotic therapy.

Written by Rupert Shepherd


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