Indications
Rivaroxaban is indicated for several therapeutic purposes. It is used to prevent venous thromboembolic events (VTE) in patients undergoing total hip or knee replacement surgeries. Furthermore, it aids in preventing stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Rivaroxaban is also employed in the treatment and prevention of deep vein thrombosis (DVT) and pulmonary embolism (PE) and to reduce the risk of recurrent DVT and/or PE. Additionally, it is indicated in combination with aspirin to lower the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. In pediatric patients, rivaroxaban is used for managing VTE from birth to 18 years and for thromboprophylaxis in children aged 2 years and older with congenital heart disease following the Fontan procedure. However, rivaroxaban is not recommended for use in patients with severe renal impairment (creatinine clearance <30 mL/min).
Pharmacodynamics
Rivaroxaban functions as an anticoagulant by binding directly to factor Xa, thereby inhibiting the amplification of the coagulation cascade and preventing thrombus formation. This mechanism of action distinguishes rivaroxaban as it does not require antithrombin III (ATIII) to exert its effects, unlike some other anticoagulants. It is administered orally, offering a more convenient alternative to parenterally administered anticoagulants like unfractionated heparin and low molecular weight heparins. Though rivaroxaban prolongs tests such as activated partial thromboplastin time (aPTT) and HepTest in a dose-dependent manner, these are not recommended for assessing its pharmacodynamic effects. Additionally, anti-Xa activity influenced by rivaroxaban is not recommended for monitoring.
Absorption
After oral administration, rivaroxaban is quickly absorbed, reaching peak plasma concentrations within 2 to 4 hours. The bioavailability of a 10 mg dose exceeds 80%. However, for doses of 15 to 20 mg, bioavailability is reduced if consumed on an empty stomach; therefore, it is recommended to take these doses with food to ensure optimal absorption.
Metabolism
Approximately two-thirds of a rivaroxaban dose undergoes metabolic processing. It is metabolized primarily through cytochrome P450 enzymes CYP3A4, CYP3A5, and CYP2J2, as well as through CYP-independent mechanisms. This metabolic pathway is crucial for understanding potential drug interactions and individual patient responses to rivaroxaban therapy.
Mechanism of Action
Rivaroxaban functions as a direct inhibitor of both free and clot-bound factor Xa, thereby interfering with the coagulation cascade at a critical juncture. Factor Xa plays an essential role in the conversion of prothrombin (factor II) to thrombin (factor IIa), a serine protease responsible for the transformation of fibrinogen to fibrin-creating the fibrin mesh that is vital for clot formation. Given that a single factor Xa molecule can produce over 1,000 thrombin molecules, the targeted inhibition provided by rivaroxaban effectively halts the amplification of thrombin production, making it a potent agent in clot prevention. Notably, the action of rivaroxaban is irreversible, underscoring its efficacy in maintaining anticoagulation control.
