FDA to Review Bleeding Events With Pradaxa

Yesterday the FDA announced that it will evaluate postmarketing reports of "serious" bleeding in patients taking the anticoagulant Pradaxa (dabigatran); although the agency doesn't say how many reports of serious bleeding have been received since the drug was approved a little more than a year ago.* The FDA is basing its analysis on data from its own pilot program, the Mini-Sentinel system, as well as submitted information to its standard reporting system, AERS.

Currently Pradaxa is only available in the United States in the form of 150- and 75-mg pills, the latter approved for renally compromised patients (CrCL 15-30 mL/min) and solely on the basis of pharmacokinetic studies. The FDA has been criticized for failing to approve the 110-mg pill, which was shown to be comparable (ie, nonsuperior) to warfarin in the large RE-LY trial (for background, start here). According to SDI's proprietary national tracking services, cited by the FDA, about 1.1 million prescriptions for Pradaxa were dispensed in the United States between October 2010 and August 2011, and 371,000 patients received Pradaxa from outpatient retail pharmacies. Not a huge population, but not insignificant either.

The FDA also advises, wisely, that comparing postmarketing reports of bleeding with Pradaxa and those with warfarin is probably not helpful, because "warfarin has been marketed for over 50 years and is well known to cause bleeding, [consequently] patients and healthcare professionals are not likely to report bleeding in association with warfarin." The agency concludes, "Thus, a simple comparison between Pradaxa and warfarin...is of limited value." The FDA also says that it's working with Pradaxa's manufacturer, Boehringer Ingelheim, to assess a range of potentially adverse postmarketing events.

AERS = Adverse Events Reporting System.

* For the prevention of stroke and other cases of systemic embolism in patients with nonvalvular a-fib.