From the Guidelines
Pradaxa (dabigatran etexilate) is a direct thrombin inhibitor that works by binding directly to thrombin, preventing it from converting fibrinogen to fibrin in the coagulation cascade, as shown in the RE-LY trial 1. This mechanism effectively blocks thrombin's ability to promote clot formation. Pradaxa is a prodrug that is rapidly converted to its active form, dabigatran, after oral administration. Unlike warfarin, which inhibits the synthesis of vitamin K-dependent clotting factors, Pradaxa directly inhibits thrombin (Factor IIa) without requiring routine blood monitoring. This provides more predictable anticoagulation effects.
- The anticoagulant effect begins within 1-2 hours after administration and has a half-life of approximately 12-17 hours.
- Pradaxa is primarily eliminated by the kidneys, so dosage adjustments are necessary for patients with renal impairment, as noted in the 2011 ACCF/AHA/HRS focused update 1.
- Common dosing is 150 mg twice daily for most patients, though 110 mg twice daily may be used in elderly patients or those with increased bleeding risk, as approved by the FDA and discussed in the 2014 AHA/ACC/HRS guideline 1.
- Unlike warfarin, Pradaxa has fewer food and drug interactions, making it easier to manage in many patients, though it lacks a specific reversal agent for emergency situations. The RE-LY trial demonstrated the efficacy and safety of dabigatran compared to warfarin in patients with nonvalvular atrial fibrillation, with a significant reduction in hemorrhagic strokes and major bleeding events 1.
From the FDA Drug Label
Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties.
The mechanism of action of Pradaxa (dabigatran) is as a competitive, direct thrombin inhibitor. It works by inhibiting thrombin, a serine protease that enables the conversion of fibrinogen into fibrin during the coagulation cascade, thereby preventing the development of a thrombus. This inhibition affects both free and clot-bound thrombin, as well as thrombin-induced platelet aggregation 2.
From the Research
Mechanism of Action of Pradaxa
- Pradaxa, also known as dabigatran, is an oral anticoagulant that inhibits thrombin, a key enzyme in the coagulation cascade 3, 4, 5.
- As a direct thrombin inhibitor, dabigatran works by selectively and reversibly inhibiting the activity of thrombin, thereby preventing the formation of blood clots 5.
- The mechanism of action of dabigatran is distinct from that of warfarin, which inhibits the production of vitamin K-dependent clotting factors 3, 6.
- Dabigatran does not require monitoring of haemostasis, unlike warfarin, which requires regular monitoring of international normalized ratio (INR) levels 3, 5.
Key Characteristics of Pradaxa
- Pradaxa is administered orally, with a recommended dose of 220 mg once-daily for certain indications 5.
- The drug has been shown to be effective in preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation, as well as in preventing venous thromboembolism after total hip or knee replacement surgery 3, 6, 5.
- Pradaxa has a similar safety profile to enoxaparin, but with a lower risk of drug-related thrombocytopenia 5.
- The drug is contraindicated in patients with severe renal impairment, and caution is advised when using it in patients with moderate renal impairment or in elderly patients (>75 years old) 5.