Dabigatran Etexilate for the Prophylaxis of Venous Thromboembolism After Hip or Knee Replacement Rationale for Dose Regimen

Dabigatran etexilate is an oral reversible direct thrombin inhibitor that offers potential practical advantages over existing anticoagulants for the prevention of venous thromboembolism after major joint replacement surgery. These include oral administration, rapid onset of action, and a predictable anticoagulant effect that obviates the need for laboratory monitoring. Evidence from 3 phase II dose-finding trials showed that dabigatran etexilate, 100 to 300 mg daily, had similar efficacy, risk of bleeding, and tolerability compared with enoxaparin. Using pharmacokinetic modeling and taking into account efficacy/safety considerations, dabigatran etexilate 150 mg and 220 mg once daily, with a half-dose on the day of surgery, were selected for further evaluation in phase III trials. These doses were selected to ensure that the risk of bleeding did not exceed that of enoxaparin. This review discusses the rationale for selection of these dose regimens based on results from phase II trials.