Reports Claim Drug Company Withheld Important Safety Information

Boehringer Ingelheim may have known how to reduce bleeding risks with Pradaxa but failed to tell FDA

/ Author:  / Reviewed by: Joseph V. Madia, MD Beth Bolt, RPh

(RxWiki News) The maker of a new anti-clotting medication may have withheld important safety information from regulators, according to several new reports.

The reports, which appear in the BMJ, claim that Boehringer Ingelheim did not share important safety information about its medication dabigatran (brand name Pradaxa) with the US Food and Drug Administration (FDA).

According to Deborah Cohen, investigations editor of the BMJ, documents show that Boehringer had evidence that monitoring plasma levels of the medication and adjusting doses accordingly could lower the risk of major bleeds. However, the company appears to have kept that information secret.

Dabigatran is a new oral anti-clotting medication used to prevent stroke in those with nonvalvular atrial fibrillation, a condition involving abnormal heart rhythms.

One of the main selling points of dabigatran, Cohen wrote, was that plasma monitoring would not be needed. In fact, official guidelines in the US, Europe and Canada have recommended dabigatran and anti-clotting medications like it partly because they don't require plasma monitoring. But the results of the BMJ investigation suggest that the evidence behind these guidelines may be incomplete.

The internal documents Cohen uncovered show that Boehinger had a fair amount of evidence showing how the bleeding risks of dabigatran could be lowered. The company found that major bleeds could be reduced by 30 to 40 percent if plasma levels of dabigatran were measured and doses were adjusted according to those measurements. However, according to the BMJ reports, it's possible that some at the company did not want this information to be known.

Boehringer maintains that plasma monitoring is not needed.

"Our scientists determined, and the Food and Drug Administration concurred, that the research does not support making dosage decisions based on plasma concentrations — a conclusion based solely on science and patient welfare," a Boehringer spokesperson told the BMJ.

The FDA approved dabigatran based on one study — the RE-LY trial (Randomised Evaluation of Long-Term Anticoagulation Therapy). Because Boehringer applied for "fast track" approval, the FDA decision was based on a review of RE-LY before it was finished rather than the standard approval process, which involves a review of two completed randomized clinical trials.

In an editorial article in the BMJ, Blake Charlton and Rita Redberg of the University of California, San Francisco, claimed that this rushed FDA review process is partly to blame for the incomplete understanding of the risks and benefits of dabigatran.

"In effect, the current situation leaves clinicians and patients the choice between the devil they know and the one they don't," Charlton and Redberg wrote.

Review Date: 
July 23, 2014
Last Updated:
November 24, 2014