The direct factor Xa inhibitor rivaroxaban

Abstract

Warfarin and heparin are the traditional mainstay anticoagulant therapies for treating thromboembolic disease. These drugs, with a documented history of utility, also have inherent difficulties in usage; in particular, the complicated monitoring and numerous drug-drug interactions of warfarin, and the need for parenteral administration of heparins. New agents have recently emerged that target specific elements of the clotting pathway. Rivaroxaban, which inhibits activated factor X (Xa), is currently in clinical trials and is the most advanced factor Xa inhibitor. The drug offers once-daily oral dosing, with no need for injections, dose titration, or frequent blood tests to monitor the international normalised ratio. It has a rapid onset of action and, although there is no specific antidote, it has a short plasma elimination half-life (about 5-9 hours). Evidence from recently published large-scale phase III clinical trials shows rivaroxaban to be superior to enoxaparin for prophylaxis of venous thromboembolism after major orthopaedic surgery. Studies have shown rivaroxaban to have a sound safety profile, with an incidence of bleeding similar to enoxaparin in phase III clinical trials. Few side effects and drug-drug interactions between rivaroxaban and common medications have been found thus far, although some interactions with potent cytochrome P450 3A4 inhibitors have been observed. It is hoped that rivaroxaban may be used as a first-line anticoagulant for prophylaxis of venous thromboembolic disease in postsurgical patients.