Dabigatran etexilate product profile
? DTIs effectively bind to, and directly inhibit the activity of circulating and clot-bound thrombin
? Thrombin plays a central role in thrombosis ? its multiple prothrombotic actions in the coagulation cascade make it a key target for therapeutic intervention in most thromboembolic diseases
? Preclinical studies in in vitro and in vivo models of thrombosis have shown dabigatran to be a potent, specific and reversible inhibitor of thrombin
? Dabigatran etexilate is a prodrug with no pharmacologic activity; once administered orally, it is rapidly absorbed and subsequently converted to the active drug dabigatran by plasma enzymes
? After oral administration of dabigatran etexilate, the plasma concentration of dabigatran reaches peak levels within 0.5?2.0 hours. Dabigatran has generally a linear pharmacokinetic profile, which means that its plasma concentration increases as the administered dose is increased. The half-life is 14?17 hours in healthy adults, which means that some anticoagulant activity remains 24 hours after administration of the last dose
? There is a good correlation between prolongation of blood coagulation assays and dabigatran plasma concentrations ? as the plasma concentration of dabigatran increases so do the activated partial thromboplastin time (aPTT), ecarin clotting time (ECT), thrombin time (TT) and international normalised ratio (INR) values
? The anticoagulant effects of dabigatran decline in parallel with its declining plasma concentration.
? Dabigatran is eliminated from the body mainly by the kidneys (up to 80%)
? Dabigatran has a favourable safety profile ? the major side effect is increased bleeding events with higher doses, which is consistent with its known pharmacologic activity
? Given that dabigatran does not undergo hepatic metabolism, there is low potential for drug?drug interactions and no potential for drug?food interactions
? In summary, dabigatran etexilate is a convenient, fixed oral dose anticoagulant, which has a rapid onset of action, provides predictable and consistent anticoagulant effects without the need for coagulation monitoring and has low potential for drug?drug interactions and no potential for drug?food interactions
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Stangier J, et al. J Clin Pharmacol 2005; 45: 555¬?63.