FDA adds new heart warning to Sanofi's Multaq

Federal health officials have added new safety warnings to the heart rhythm drug Multaq after company studies linked the pill to higher rates of heart attack, stroke and death in a subset of patients.

The new label, posted online Monday, highlights a study in which Multaq doubled the risk of heart-related complications in patients with permanent atrial fibrillation, a condition in which the heart's chambers pump out of sync. The revised label stresses that Multaq is only approved for the short-term form of the condition and a related ailment known as atrial flutter. Despite such language, doctors routinely prescribe drugs for conditions not listed on the labeling approved by the Food and Drug Administration.

The label, written in cooperation with drugmaker Sanofi, 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. The FDA said Monday Multaq remains a beneficial drug when used appropriately.

The warning label is the latest setback for a drug that Sanofi once touted as a potential blockbuster. When first approved in 2009, Multaq was the first new drug in a decade for atrial flutter and atrial fibrillation - related heart disorders in which the organ's upper chambers beat rapidly and ineffectively. Both conditions can cause stroke and death, in some cases. Multaq has been subject to a series of safety concerns, both before and after its approval in the U.S.

EU 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 Sanofi study of more 3,200 patients there were 25 deaths in the Multaq group compared with 13 in the placebo group. All 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. The French drugmaker estimates there are 2.5 million atrial fibrillation patients in the U.S., and another 4.5 million in the EU. In patients with paroxysmal, or temporary, atrial fibrillation, irregular heartbeats usually last less than 24 hours. Over time the incidents can become more frequent, developing into permanent atrial fibrillation, in which normal heart rhythm can no longer be achieved.

About 278,000 people in the U.S. have received prescriptions for Multaq as of October, according to the FDA. Sanofi reported about $224 million in sales for the drug in 2010, with most prescriptions written in the U.S.

Since last year the FDA has approved two other drugs for atrial fibrillation: Johnson & Johnson's Xarelto and Boehringer Ingelheim's Pradaxa. Both drugs are marketed as alternatives to the hard-to-use warfarin, a 60-year old drug that doctors often prescribe for atrial fibrillation. Too much warfarin can cause dangerous internal bleeding, and too little can result in strokes.

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, a condition where the heart no longer pumps enough blood. Many patients in the study did not even have the irregular heart rhythm Multaq was designed to treat.

So Sanofi did another study that included 4,600 patients with atrial fibrillation but without severe heart failure. This time results were positive: Multaq helped reduce hospitalization and death from heart-related problems by 24 percent, a claim that appears on the drug's label.

Multaq already carries a 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. Common side effects of the twice-a-day tablets include fatigue, loss of strength, diarrhea, nausea and vomiting.