Rivaroxaban (DB06228): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Rivaroxaban, a small molecule oxazolidinone derivative, represents a significant milestone in anticoagulant therapy as the first orally active, direct inhibitor of coagulation Factor Xa (FXa). Marketed principally under the brand name Xarelto, it has fundamentally altered the landscape of thromboprophylaxis and treatment, offering a more predictable and convenient alternative to traditional vitamin K antagonists (VKAs) such as warfarin. Its mechanism of action, the direct, competitive, and reversible inhibition of both free and clot-bound FXa, allows for rapid onset of action and a consistent anticoagulant effect without the need for routine coagulation monitoring. This predictable pharmacological profile has enabled the development of fixed-dose regimens for a broad spectrum of clinical indications.

The clinical utility of rivaroxaban is supported by an extensive program of phase III clinical trials, including ROCKET AF for stroke prevention in non-valvular atrial fibrillation (NVAF) and the EINSTEIN program for the treatment and secondary prevention of venous thromboembolism (VTE). These studies have established its non-inferior efficacy compared to standard of care, coupled with a distinct safety profile characterized by a reduced risk of intracranial hemorrhage but an increased risk of gastrointestinal bleeding. Further trials have expanded its use to VTE prophylaxis after major orthopedic surgery, risk reduction in chronic coronary and peripheral artery disease, and, more recently, to pediatric populations for VTE treatment and thromboprophylaxis post-Fontan procedure.