The Institute for Safe Medication Practices has identified a potential drug safety signal for dronedarone (Multaq, Sanofi-Aventis). The potential problem is outlined in QuarterWatch: 2010 Quarter 1, a publication of the ISMP that monitors FDA MedWatch reports, and was written about on the Pharmalot blog.
The report concludes:
Evidence is accumulating that the risks of the new heart drug dronedarone have been underestimated, and its clinical benefits are limited. New adverse event reports that the drug may cause or worsen heart failure, trigger irregular heartbeats, and interact with other drugs frequently taken by heart patients raise serious doubts about its suitability for widespread use.
The QuarterWatch report is based on 387 domestic serious adverse events in which dronedarone was the primary suspect drug. Three-quarters of the events were reported by health professionals. The report discusses three separate safety issues related to dronedarone:
- Dronedarone may cause new or worsened heart failure. The report notes that as a result of the ANDROMEDA trial dronedarone is not indicated in heart failure patients, and yet heart failure accounted for a quarter of the reported cases.
- Dronedarone might trigger or worsen existing arrhymthias. The report mentions 8 potential case of bradycardia, 47 cases of atrial tachycardia, and 13 cases of ventricular tachycardia. The authors write that “the original signal for dronedarone was our discovery that, in the first quarter of 2010, dronedarone accounted for more reported cases of these kinds of rhythm disturbances than any other drug we monitor.”
- Dronedarone might have adverse effects on the kidneys. The report cites 15 cases of kidney failure including 4 cases of acute kidney failure.
The authors write that they talked about the cases with Sanofi-Aventis:
The company said it believed that some studies showed that the reporting rate for adverse drug events may be higher during the first two years after introduction. The company also noted that the FDA was itself evaluating at least two signals in the adverse event reports for dronedarone—heart failure and Torsades de Points…
Finally, the report identifies “a serious lapse in the Medication Guide which explains dronedarone risks to patients.” Although the drug is contraindicated in pregnant women the Medication Guide for patients states:
It is not known if MULTAQ will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
Here is the final word on dronedarone in the report:
We have seldom seen a drug with so many issues in so many areas of its safety profile. It caused cancer and birth defects in animals, has potentially serious interactions with other important drugs for atrial fibrillation, may cause or worsen heart failure, causes new heart rhythm disturbances in some patients and doubled mortality in patients with severe heart failure. In the only head-to-head trial with an existing treatment, dronedarone was markedly less effective than amiodarone and did not demonstrate any statistically significant safety advantage.
Editorial comment: Some readers may recall that dronedarone has been the topic of multiple posts on this site. I have raised questions on several occasions about the excessive marketing of this agent, including multiple dubious “educational” programs and initiatives.
The Multaq thread on this site started with a question about AFibProfessional.org,a site sponsored by Sanofi and jointly run by the ACC and the Heart Rhythm Society (HRS). They defined the site as “a unique collaboration to address atrial fibrillation for the cardiology community.” The “About Us” page of the site states:
The sponsor had no involvement in the selection of content or the volunteer participating experts.
My posts (see below) raised questions about the independence of the site. Here’s what I want to know now: will AFibProfessional.org now give full and fair coverage to the QuarterWatch report about dronedarone?
Previous CardioBrief coverage of Multaq:
- Pieces of a puzzle: Multaq, Sanofi, ACC, HRS, Prystowsky, AF Guidelines
- More Multaq: Prystowsky whack-a-mole, ACC responds, Sanofi overtures to EPs
- Prystowsky lecture resurfaces, this time with COI disclosures
- Even more questions about Multaq and Prystowsky, alas
- Can we trust ATHENA?
- A missing piece of the Multaq puzzle finally appears: DIONYSOS published to little fanfare