Dabigatran acts through competitive and reversible inhibition of both free and fibrin-bound thrombin activity. By inhibiting thrombin, the conversion of fibrinogen to fibrin, which forms the clot, is blocked. Additionally, the activity of factor XIII, responsible for clot stabilization, is inhibited (fibrin does not assume its cross-linked stabilized form). The drug also inhibits thrombin-induced platelet aggregation.
Dabigatran is rapidly absorbed from the gastrointestinal tract; however, its bioavailability is low, ranging from 3–7%. Peak plasma concentration is reached 0.5–2 hours after oral administration. Reduced absorption and prolonged time to peak concentration (approximately 6 hours) have been observed in postoperative patients (particularly on the first day after surgery). Co-administration with food also delays peak concentration by approximately 2 hours. Administration of the drug without the HPMC capsule shell increases bioavailability by approximately 75%; therefore, proper administration must be observed (capsules should be swallowed whole).
Dabigatran is 34–35% bound to plasma proteins.
The drug, in the form of dabigatran etexilate, is a prodrug that undergoes conversion to the pharmacologically active dabigatran. The principal metabolic reaction is esterase-mediated hydrolysis. Cytochrome P450 is not involved in the metabolism of the drug.
Dabigatran is excreted 85% unchanged in the urine, while the remaining portion of the dose is excreted in bile via feces as glucuronide conjugates. The elimination half-life following multiple dosing is 12–14 hours.
⚠️ Warnings
Treatment with dabigatran may cause major bleeding (at any site). The risk of bleeding is increased in patients over 75 years of age, those with congenital coagulation disorders, and patients concomitantly receiving antiplatelet agents, among others. In cases of very severe bleeding, treatment must be discontinued. The use of proton pump inhibitors (e.g., pantoprazole, omeprazole) is recommended for bleeding prevention. Assessment of dabigatran's anticoagulant effect using the International Normalized Ratio (INR) does not yield reliable results; therefore, other methods are recommended, such as diluted thrombin time, activated partial thromboplastin time (aPTT), and ecarin clotting time. Planned surgical procedures may require discontinuation of dabigatran due to the risk of major bleeding. This does not apply to cardioversion and catheter ablation for atrial fibrillation. Prolonged drug clearance in patients with renal impairment should be taken into account. The minimum interval between the last dose of dabigatran and the start of the procedure is 24 hours, and for more invasive procedures, 2–4 days. When emergency surgery is required, the specific reversal agent for dabigatran (idarucizumab) should be administered. In such cases, dabigatran may be resumed after 24 hours, provided the patient's condition is clinically stable.
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