Multaq continues to disappoint

What should I have told the doctor who recently asked me about dronedarone (Multaq)?

“Supposedly, it’s [Multaq] just like Amiodarone, but without the side effects?” he asked.

Gosh…Should I, or shouldn’t I?

I took a big cleansing breath, reminding myself to stay civil, as at least Sanofi-Aventis, the makers of Multaq, sponsor a cycling team. Then I gave him my long answer:

I started with the fact that Multaq barely made it through the approval process. One of the original studies with Multaq (ANDROMEDA), a randomized trial of Multaq in patients with severe heart failure, showed that patients who took the drug were twice as likely to die.

Multaq eventually won approval for use in patients without significant heart failure and mild forms of AF, based on the results of the ATHENA trial—which randomized 4628 patients with non-permanent AF to either standard therapy or standard therapy plus Multaq. The ATHENA investigators didn’t exactly say that Multaq works, rather they claimed that it reduced a composite of hospitalizations and death.

This started the marketing machine in motion, the likes of which I have not ever witnessed. Paid experts, “thought leaders,” as they are called, touted Multaq in endless venues—at special CME events, on the internet, at national meetings and of course, during evening dinners. There were posters, TV and magazine ads, lunches, breakfasts, key chains, and tee shirts, but not logo’d pens.

When doctors started using Multaq to treat AF they found that the drug did not suppress AF-episodes. Now, to be fair, no AF drug works much more than 50% of the time, but Multaq almost never works. Since it was approved, I have yet to see a single patient in which Multaq suppressed AF for more than 6 months.

Not only does Multaq not work in AF-suppression, the drug also causes significant side effects. More than a small number of patients report intolerable GI adverse effects—diarrhea and nausea are the most common. Additionally, the drug may cause excessive lowering of heart rate, and insomnia, both of which contribute to an AF patient’s chief complaint, fatigue.

Thus far, we could summarize Multaq as an expensive, aggressively marketed AF drug which doesn’t work and often makes people feel ill, though less frequently hospitalized.

“At least it was safe,” said the company.

Wrong.

A recent report suggested that Multaq may be associated with unpredictable and abrupt-onset liver failure. This was distressing enough, but yesterday, Sanofi announced that it was terminating its latest study, called the PALLUS trial–an investigation into whether Multaq would work as a rate-control drug in patients with permanent AF. The trial was stopped prematurely because of an increased rate of cardiovascular events in patients who took Multaq. Taken together, and along with the original ANDROMEDA trial, these reports suggest that Multaq isn’t a very safe drug.

Whew…

That was a long discussion for a doctor’s lounge question.

I could have just said, “I cannot recommend Multaq to my patients with AF.”

JMM

P.S. My colleague, Dr Wes Fisher has this outstanding, much more detailed and very professional summary of the Multaq debacle.

Here is a list of my previous posts on Multaq.