January 4, 2011 (Silver Spring, Maryland) — Sanofi-Aventis has sent US healthcare professionals a letter warning them about cases of rare but severe hepatic injury associated with use of the antiarrhythmic drug dronedarone (Multaq), the company has informed heartwire . In two instances, liver transplants had to be performed.
The FDA has also issued a "safety communication" .
The Sanofi letter describes the possibility of liver-function-test abnormalities and hepatocellular injury in patients taking the product, but the company is stressing that no causal association between the drug and liver injury has yet been established.
Healthcare professionals should consider periodic liver-function tests in patients taking dronedarone, especially in the first six months of treatment, the letter states, and patients should be advised to report any symptoms suggestive of liver injury immediately.
The labeling for dronedarone will also be revised, Sanofi confirmed to heartwire in a statement, adding that it has been in communication with the FDA over alterations to the prescribing information. And it adds that it is also "working closely on this matter" with the European Medicines Agency (EMA) and health authorities in other countries where dronedarone is approved or awaiting approval.
EMA spokesperson Monika Benstetter told heartwire that the EMA has received the data on the liver-injury cases and that the issue has been placed on the agenda for next week's monthly meeting of the Committee for Medicinal Products for Human Use(CHMP).
Dronedarone had a bumpy road to approval in the US--based primarily on the ATHENA trial, which has had its critics. The drug's balance of virtues and limitationshas been much discussed, with the most recent criticism being that it may be proarrhythmic or promote heart failure. The drug was eventually approved with a risk evaluation management Strategy (REMS) with the goal of preventing its use in patients with severe heart failure or who have recently been hospitalized with HF. Consideration was given to the fact that the existing first-tier drug choice for AF, amiodarone, has some unusually serious dosing and safety issues. A substitute for amiodarone in AF has been long sought.
Heartwire from Medscape © 2011 Medscape, LLC
Cite this: Dronedarone Linked to Severe Liver Injury - Medscape - Jan 14, 2011.