The Food and Drug Administration is looking into reports of serious bleeding events associated with the anticoagulant dabigatran, the agency announced on Dec. 7.
Dabigatran (Pradaxa) was approved in October 2010 for long-term anticoagulation in patients with atrial fibrillation. The bleeding events, about which the FDA’s Division of Drug Information did not provide specifics, were reported to the Adverse Events Reporting System and were evaluated in November.
"While serious, even fatal events have been reported, the FDA is analyzing the events to determine whether the reports of bleeding in patients taking Pradaxa are occurring more commonly than would be expected, based on observations in the large clinical trial that supported the approval of Pradaxa," the agency wrote.
That trial was the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy), a noninferiority study of 18,113 patients with nonvalvular atrial fibrillation and at least one other risk factor for stroke. Only the higher of two doses tested, 110 mg and 150 mg, was approved, apparently because it was more effective than warfarin in preventing stroke and systemic embolism. The 150-mg dose was found to be associated with a significantly increased risk of major GI bleeding, compared with warfarin, but also with a significant reduction in life-threatening and total bleeding.
The agency acknowledges that determining whether the reported events are occurring more than with dabigatran’s alternative, warfarin, is problematic. "Because warfarin has been marketed for over 50 years and is well-known to cause bleeding, patients and healthcare professionals are not likely to report bleeding in association with warfarin."
The FDA reaffirmed its belief that "the benefits of Pradaxa continue to exceed the potential risks when the drug is used appropriately." Further, it urged that health care professionals continue to prescribe Pradaxa, which is manufactured by Boehringer Ingelheim, following the recommendations in the drug label.