Multaq Subject to New FDA Restrictions

U.S. drug regulators yesterday announced new restrictions for Multaq, 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 because of its association with serious heart problems, including heart failure, stroke and death.

Multaq was approved by the FDA in 2009 to treat people with temporary atrial fibrillation. According to a report from The Wall Street Journal, Multaq was expected to be a $1-billion-a-year seller because millions of people suffer from that disorder. Since its approval, Multaq has been prescribed to more than 500,000 patients and is available in 39 countries, and had world-wide sales of $179 million in the first half of 2011.

The FDA began conducting a safety review of Multaq in January. 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 clinical trial, was evaluating the use of Multaq in people over 65 with permanent atrial fibrillation. As we reported previously, PALLAS was halted over the summer after Multaq-treated subjects experienced a higher-than expected frequency of adverse heart events.

According to a Drug Safety Communication issued by the FDA yesterday, 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 yesterday’s 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.

As a result of its safety review, the FDA said the Multaq drug label has been revised with the following changes and recommendations:

• 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.
• Healthcare professionals should monitor heart (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.
• 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 FDA’s action comes just months after European regulators took steps to restrict the use of Multaq. In September, a committee of the European Medicines Agency (EMA) also advised that Multaq not be used in most people with permanent atrial fibrillation, but left it on the market for some patients the intermittent form of the disease. However, that agency also cautioned doctors to consider other atrial fibrillation treatments before they prescribe Multaq.