WASHINGTON -- The FDA said it will begin a safety review of reports of excess bleeding associated with dabigatran (Pradaxa), an oral direct thrombin inhibitor that is approved for prevention of stroke in patients with nonvalvular atrial fibrillation.
The FDA's announcement comes a month after post-marketing reports of about 50 cases of fatal bleeding worldwide surfaced.
The FDA said it wants to determine whether the reports of bleeding are occurring more commonly than would be expected.
In the RE-LY clinical trial, which compared two doses of dabigatran (150 mg bid and 110 mg bid) with warfarin in more than 18,000 patients, the bleeding rates between the two arms were similar.
When the FDA approved the drug in October 2010, it limited its approval to two doses: 150 mg bid and 75 mg bid, a decision that was immediately questioned because the 75 mg dose had never been tested in a clinical trial. Last spring, the New England Journal of Medicine published a commentary in which two FDA researchers involved in the approval decision explained the agency's reasoning, acknowledging a prevailing concern about the potential for excess bleeding.
When the bleeding reports surfaced last month, a spokesperson for drug-maker Boehringer Ingelheim said dabigatran's safety profile was in line with that seen during the clinical trial.
In the meantime, the FDA said that at this time it "believes that Pradaxa provides an important health benefit when used as directed and recommends that healthcare professionals who prescribe Pradaxa follow the recommendations in the approved drug label." The agency advised patients to keep taking the drug and to consult their physicians if necessary.