Earlier this year, I wrote about the spotty safety record associated with Multaq, which is also known as dronedarone (The FDA and the Saga of Multaq – When is enough, enough?).

Multaq, an atrial fibrillation drug, has only been on the market since July of 2009, but has generated record volumes of safety alerts and changes to its warning labels in the months that have followed.

Even before its approval in 2009, Multaq and its manufacturer Sanofi-Aventis were under a cloud of controversy, as approval of Multaq by the FDA was initially rejected in 2006 in the aftermath of reports of patient deaths attributed to the drug.  We can only speculate how the FDA overcame its concerns and ultimately approved the drug in 2009, although it is well known that the FDA is under tremendous political pressure to approve new drugs and often chooses to require extensive warnings in lieu of denying approval.  I also suspect that there is a great deal of finger-pointing and hand wringing at the FDA water cooler this week, as the FDA issues yet  another safety alert to doctors and patients discouraging use of Multaq.

The safety issues swirling around Multaq include:

  • heart failure
  • fatal ventricular arrhythmias
  • interstitial lung disease
  • pulmonary fibrosis
  • pneumonitis
  • kidney problems including elevated creatinine and blood urea nitrogen (BUN) levels
  • long QT syndrome
  • torsade de pointes
  • liver toxicity
  • acute liver failure
  • serious liver injuries

The drug has also been linked to dangerous drug interactions with Warfarin (also known as Coumadin), and use of Multaq has been discouraged in patients who are elderly, have a history of serious heart disease, congestive heart failure, or diabetes, or those who have suffered a stroke in the past.

In July of 2011, the FDA announced that it was evaluating new safety data relating to Multaq, which arose in a clinical study that was evaluating whether use of Multaq should be approved in patients with permanent atrial fibrillation as opposed to only those patients with short-term atrial fibrillation or atrial flutter.  Obviously, the market for patients with chronic atrial fibrillation (who need medication on a daily basis for the rest of their lives) is far more lucrative than for those who are suffering a temporary problem with their heart rhythm.

On December 19, 2011, the FDA announced that it had completed its most recent re-review of the safety of Multaq and made a number of recommendations to patients and their cardiologists.   The FDA concluded that use of Multaq in patients with permanent atrial fibrillation increased the risks of serious heart problems, including death, stroke, and heart failure.  The FDA was focused in particular on data from two recent studies, which showed a 200% increased risk or a doubling of the risk for cardiovascular adverse events in patients taking Multaq.  Patients who are currently taking Multaq need to carefully review all of the FDA safety alerts with their physicians, and should not discontinue taking Multaq without consulting their doctor in order to minimize potential complications.

The latest FDA recommendations from Multaq are likely to be the death-knell for the drug, as they recommend that physicians not prescribe the medication unless they are certain that the drug will be effective in converting the patient’s atrial fibrillation; require monitoring every three months to determine whether there is efficacy and to screen for adverse events; should not be used in patients who require long-term therapy for atrial fibrillation or atrial flutter; and should only be given to patients along with antithrombotic therapy (i.e., drugs that decrease the risks of blood clots – provided those drugs like Coumadin are not otherwise contraindicated with Multaq).

The FDA still contends in its Safety Alert that Multaq provides benefits to a limited subset of patients, which is of little comfort since the FDA must believe that a drug’s benefits outweigh its risks – at least to some segment of patients in order to substantiate its decision to allow the drug to remain on the market.

The fact that Multaq remains on the market is terribly confusing to patients, but not particularly surprising to those of us who are intimately involved in drug litigation and have seen the holes in our drug safety system.  Patients want drug recalls and assume that dangerous or defective drugs are in fact recalled.  The truth, however, is that the nasty “R word” is infrequently uttered by regulators or drug companies.  The FDA rarely recalls drugs, except for those that are contaminated or defective due to improper manufacturing practices.  Drug manufacturers also rarely “recall” their drugs. An official “recall” has legal significance and makes it more difficult for pharmaceutical companies to hide behind tort reform laws that were passed to make it difficult for patients to sue when they suffer catastrophic injuries or die from bad drugs.  If there is a drug that the FDA wants recalled, the drug manufacturer is typically informed of the FDA’s desire and, magically (but after consulting with marketing, PR, and crisis management advisors), the drug manufacturer will announce a “market withdrawal,’ a phrase that likely has been tested amongst focus groups and found to be less alarming than a “recall.”

After litigating drug and medical device cases for nearly 18 years,  the issues surrounding Multaq and Sanofi-Aventis are, sadly, quite familiar.  If I were to look into my crystal ball, I predict that Multaq will not be around in a year, so, thankfully, no more patients will be harmed or die as a result of the product.  My prediction is that the drug will not be recalled by either the FDA or the manufacturer (which could easily pull it from the market tomorrow if it were so inclined and has the obligation to do if the drug is truly defective and unreasonably dangerous to patients).    Rather, it will be economic forces in my estimation that will lead to Multaq riding off into the sunset over the next 12 months.

Health insurers do not like to pay for drugs that are dangerous, especially those that have the potential to cause expensive hospitalizations and injuries (like liver failure), so they will likely push Multaq off of their preferred drug (or formulary) lists.  When the health insurers will not pay for the drug, few patients can afford to pay for them on their own.  Even if the health insurers continue to pay for the drug, it is likely that patients will hear something in the media regarding Multaq and ask their physicians if the benefits of the drug outweigh the risks, which likely will be answered in the negative.  Use of Multaq will now also be more expensive and burdensome to patients due to the need for additional office visits and testing in order to monitor for risks associated with taking the drug, which likely will result in further declines in patient demand for the product. And, one can always count on Sanofi-Aventis’ competitors to pile on and make certain that prescribers are informed about the latest FDA safety alert, requirements for patient monitoring, and the cloud hanging over Multaq.   At the end of the day, if no one wants to buy Multaq, then Sanofi-Aventis will likely stop selling the drug (or at least stop actively promoting it to doctors) and instead turn its attention to the next billion dollar blockbuster.  While a recall would be much simpler, as long as patients are no longer being harmed by a bad drug, a market withdrawal achieves the same objective (eventually) and is the closest that we usually see with our drug safety system, which is sadly engineered to choose  profits over patients.

So, getting back to the title of my blog in October of 2011, when is enough, enough with regard to Multaq?  Apparently, not today (at least for the FDA and Sanofi-Aventis), but I suspect that December 19, 2011, was the date that enough was enough for frustrated physicians and frightened Multaq patients, who will seek out safer treatments for atrial fibrillation.