Dabigatran etexilate -direct thrombin inhibitor

Dabigatran etexilate – direct thrombin inhibitor

Dabigatran etexilate – direct thrombin inhibitor: Dabigatran is an alternative to warfarin for the prevention of stroke and systemic thromboembolism in patients with paroxysmal or permanent atrial fibrillation and risk factors for stroke or systemic embolization, but do not have a prosthetic heart valve or hemodynamically significant valve disease, severe renal failure (creatinine clearance less than 15 mL/min) or advanced liver disease (impaired baseline clotting function). An important trial which evaluated dabigatran was the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial by Stuart J Connolly, Michael D Ezekowitz, Salim Yusuf, John Eikelboom, Jonas Oldgren, Amit Parekh, Janice Pogue, Paul A Reilly, Ellison Themeles, Jeanne Varrone, Susan Wang, Marco Alings, Denis Xavier, Jun Zhu, Rafael Diaz, Basil S Lewis, Harald Darius, Hans-Christoph Diener, Campbell D Joyner and Lars Wallentin the RE-LY Steering Committee and Investigators [1].

Dabigatran etexilate is a prodrug which is converted to dabigatran a direct thrombin (Factor IIa) inhibitor, by a mechanism independent of cytochrome P-450. This independence makes drug-drug and diet-drug interaction less likely, unlike warfarin which has numerous such interactions.

It may be noted that the half-life of dabigatran is 12 to 17 hours and there is no specific antidote for dabigatran.

Since dabigatran has to be taken twice daily and there is a greater risk of non hemorrhagic side effects with dabigatran, there may not be any benefit in switching over patients on warfarin with excellent control of INR to dabigatran. In those with erratic control of INR, dabigatran is definitely an alternative option.

References

  1. Stuart J Connolly, Michael D Ezekowitz, Salim Yusuf, John Eikelboom, Jonas Oldgren, Amit Parekh, Janice Pogue, Paul A Reilly, Ellison Themeles, Jeanne Varrone, Susan Wang, Marco Alings, Denis Xavier, Jun Zhu, Rafael Diaz, Basil S Lewis, Harald Darius, Hans-Christoph Diener, Campbell D Joyner, Lars Wallentin, RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139 –51.