Dabigatran etexilate: a new challenge for emergency physicians and toxicologists

June 18, 2011, 4:24 pm

★★★½☆

Dabigatran Etexilate: A New Oral Thrombin Inhibitor. Hankey GJ, Eikelboom JW. Circulation 2011;123:1436-1450.

Abstract

Dabigatran etexilate is an anticoagulant recently approved by the FDA for the prevention of stroke in patients with atrial fibrillation (and also used for treating acute venous thromboembolism). Dabigatran etexilate is actually a pro-drug with no anticoagulant activity; once absorbed, it is rapidly hydrolyzed by esterases in the GI tract, blood, and liver into dabigatran, a thrombin inhibitor. Although costly, dabigatran etexilate has several potential advantages over warfarin.  The pharmacokinetics are quite predictable, simplifying dosing and eliminated the need for frequent blood tests and monitoring.  In addition, the drug requires no dietary restrictions and has relatively few drug interactions (at least that are know at this point).

Because it is so new, there is very little experience treating patients on dabigatran etexilate who present with major bleeding or drug overdose. Although many of the recommendations on dealing with these situations incorporated in this (and other) articles are based on speculation, emergency physicians and toxicologists should be familiar with current thinking on the topic.  This article would be a good place to start.

Some key points:

  • peak anticoagulation effects occur 0.5 – 2.0 hours after ingestion
  • dabigatran is primarily eliminated by the kidneys
  • there are potential drug interactions with quinidine, ketoconazole, amiodarone, rifampicin, and verapamil
  • although not perfect, the best tests for evaluating the extent of anticoagulation in patients taking dabigatran etexilate seem to be aPTT and thrombin time
  • although there is no specific antidote that will reverse the effects of dabigatran etexilate, the use of recombinant activated factor VII or prothrombin complex concentrates can be considered in patients with life-threatening bleeding (this recommendation is based only on limited non-clinical data — that is, it’s largely speculation)
  • dabigatran etexilate is well-adsorbed to activated charcoal
  • dabigatran etexilate is susceptible to hemodialysis

Two other good sources for information about dabigatran etexilate are Jim Roberts’ discussion in Emergency Medicine News, and a video talk from hqmeded.com by Dr. Nathaniel L. Scott of the Department of Emergency Medicine at Hennepin County Medical Center.

2 Comments:

  1. Pradaxa: a new challenge for emergency physicians and toxicologists » The Poison Review | Pharmacy Technician Source Says:

    […] Posted by admin on Jun 20, 2011 via thepoisonreview.com […]

  2. The Cynical Pharmacist Says:

    According to the manufacturers data, about 16% of patients can be expected to experience a bleed.

    I can see topical thrombin products possibly being effective for external bleeding situations, but like you said, without an effective reversal agent, internal bleeds could cause serious problems. Unfortunately, I’m sure we’ll be hearing about it soon.