March 13th, 2013

FDA Officials Calm Concerns Over Excessive Bleeding with Dabigatran

Concerns over excessive bleeding complications with dabigatran (Pradaxa, Boehringer Ingelheim) as compared with warfarin are most likely due to the heightened sensitivity and vigilance that can accompany a new drug, according to FDA officials in a perspective published online in the New England Journal of Medicine.

“We believe that the large number of reported cases of bleeding associated with dabigatran provides a salient example of stimulated reporting,” write Mary Ross Southworth, Marsha Reichman, and Ellis Unger. “In this case, such reporting provided a distorted estimate of the comparative bleeding rates associated with dabigatran and warfarin in clinical practice.”

Although the pivotal RE-LY trial found no significant difference in bleeding risk between dabigatran and warfarin, postmarketing reports received through the FDA Adverse Event Reporting System (FAERS) raised the possibility that dabigatran may not have been as safe in clinical practice as it had been in clinical trials.

One theory investigated by the FDA is that dabigatran may have been used differently or in different patient populations than had been studied in RE-LY and as indicated by the FDA. However, an FDA review of the FAERS reports found “no indication that dabigatran was not being used in accordance with its labeled directions.”

The FDA then used insurance and administrative data from the FDA Mini-Sentinel database to quantify the relationship between bleeding complications and new use of dabigatran and warfarin. The review found no greater risk for bleeding associated with dabigatran than with warfarin. The authors say that the FDA is conducting additional assessments to examine the issue.

They write that postmarketing surveillance of dabigatran will continue, though their current perspective is upbeat: “We believe that dabigatran provides an important health benefit when used as directed.”

One Response to “FDA Officials Calm Concerns Over Excessive Bleeding with Dabigatran”

  1. Hiteshi K.C. Chauhan, MD says:


    Though the FDA Mini-Sentinel Database upholds the Dabigatran promise, till more light is shed on its bleeding complications, an open and shut case of ‘assess your patient diligently before putting him/her on it’.