The FDA have added new safety warnings to the heart rhythm drug Multaq, (dronedarone) after Sanofi company study linked the medication to higher rates of heart attack, stroke and death in a subset of patients. The FDA completed a safety review of dronedarone, which showed that the heart drug increased the risk for serious CV events, including death, when used by patients with permanent atrial fibrillation.
The review was based on data from the PALLAS and ATHENA trials. As a result of the review, the FDA has provided new information and recommendations for use of dronedarone to manage the potential serious CV events associated with the drug, according to a statement from the agency.
The boxed warning highlights the results of a study in which Multaq doubled the risk of heart-related complications in patients with permanent atrial fibrillation. The revised label indicates that Multaq is only approved for the short-term form of atrial fibrillation and atrial flutter. Doctors routinely prescribe drugs for conditions not listed on the labeling approved by the FDA, a process called “off label prescribing.”
The label, instructs doctors to check patients’ heart rhythm at least once every three months. If patients appear to have the permanent form of atrial fibrillation, Multaq should be discontinued.
When first approved in 2009, Multaq was the first new drug in 10 years for atrial flutter and atrial fibrillation. Both conditions can cause stroke and death. Multaq has been subject to a series of safety concerns, both before and after its approval in the U.S.
European Union health officials have already restricted Multaq’s use based on the same safety information. In September the European Medicines Agency said that the drug should only be used after other treatments for atrial fibrillation have been tried.
In the study that triggered the warning, Sanofi recorded 25 deaths in the Multaq group compared with 13 in the placebo group. All 3,200 the patients in the study were older than 65 and had permanent atrial fibrillation.
Atrial fibrillation is the most common heart rhythm disorder and a frequent contributor to stroke. About 278,000 people in the U.S. have received prescriptions for Multaq as of October, according to the FDA.
The FDA originally rejected the French drugmaker’s request to approve Multaq in 2006. That was after a widely publicized study showed patients in the group taking Multaq were twice as likely to die as patients in the comparison group.
But Sanofi said the study involved patients with severe heart failure and many of them did not even have the irregular heart rhythm Multaq was designed to treat.
Multaq already carries another black box warning, the most serious type of warning. It says that the drug can cause severe complications, including death, in people with recent severe heart failure and should not be used by them.
The new label changes for the drug include the following:
Dronedarone should not be prescribed to patients with permanent atrial fibrillation (those who cannot or will not be converted into normal sinus rhythm) because of the twofold risk of cardiovascular death, stroke, and heart failure in such patients.
Patients on the drug should be monitored via ECG every three months and patients in atrial fibrillation should discontinue the drug or be cardioverted if that is clinically indicated.
Patients prescribed dronedarone should receive appropriate antithrombotic therapy.
In January, the FDA alerted healthcare professionals to the potential for liver damage from dronedarone based on two reported post-marketing case reports of acute liver failure that required transplantation. The agency recommended periodic liver enzyme tests, especially in the first six months of treatment.