UMEM Educational Pearls

Title: Reversing Dabigatran with Idarucizumab

Keywords: dabigatran, bleeding, idarucizumab, reversal (PubMed Search)

Posted: 7/6/2015 by Bryan Hayes, PharmD (Emailed: 7/9/2015) (Updated: 7/9/2015)
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The New England Journal of Medicine and Lancet both published studies evaluating idarucizumab for reversal of dabigatran. It is a monoclonal antibody fragment that binds dabigatran with high affinity. Dr. Ryan Radecki summarizes the two articles on his EM Lit of Note blog.

Here are a few take home points from these early studies:

Both studies were funded by Boehringer Ingelheim, who not suprisingly also markets dabigatran. Skepticism is always welcome when the same company makes the drug and the antidote.
The Lancet study was conducted in healthy volunteers, while the NEJM study was conducted in patients needing reversal but lacked a control group.
Idarucizumab seems to reverse laboratory markers of anticoagulation from dabigatran rapidly and completely, including dilute thrombin time and ecarin clotting time. Not all institutions have these assays available.
The dose that seems to 'work' the best is 5 gm given IV (two-2.5 gm infusions given no more than 15 minutes apart).
Median investigator-reported time to cessation of bleeding was 11.4 hours in the NEJM study.
21 of the 90 patients in the NEJM study had 'serious adverse effects' including thrombotic events.
The acquisition cost of this medication will most assuredly be high if and when it is FDA-approved in the U.S.

References

Pollack CV, et al. Idarucizumab for dabigatran reversal. N Engl J Med. 2015 Jun 22. [Epub ahead of print, PMID 26095746]

Glund S, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in health male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet. 2015 Jun 15. [Epub ahead of print, PMID 26088268]

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