Rivaroxaban (CAS: 366789-02-8)

Basic Information

Rivaroxaban (BAY 59-7939) is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceutica. It is an orally activedirect factor Xa inhibitor. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects lasts 8 to 12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible.

There is currently no specific way to reverse the anticoagulant effect of rivaroxaban in the event of a major bleeding event, unlike warfarin.

Medical uses

Rivaroxaban can be used to prevent strokes in those with atrial fibrillation due to causes other than heart valvedisease, and at least one additional risk factor for stroke (congestive heart failure, hypertension, age, diabetes, and prior stroke)

Rivaroxaban can also be used to prevent the formation of blood clots in the veins (deep venous thrombosis) in adults who have had an operation to replace a hip or knee and for treatment and prevention of acute deep venous thrombosisin adults. It can not be used for prevention of venous thrombosis in hospitalized medically ill patients.

Rivaroxaban is not indicated for prosthetic heart valves or for mitral stenosis.

Rivaroxaban is not indicated as an add-on treatment for dual antiplatelet therapy in the secondary prevention of coronary incidents (double and triple therapy). In Europe, however, a 2.5-mg twice-daily dose was approved by the European Commission after a recommendation by the European Medicines Agency (EMA) for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine.

Adverse effects

According to a systematic review, adverse effects of new anticoagulants (dabigatran, rivaroxaban and apixaban) compared with warfarin were lower for fatal bleeding and hemorrhagic stroke, numerically lower for major bleeding, numerically higher for gastrointestinal bleeding, and higher for discontinuation due to adverse events. Bleeding risks may be increased for persons older than 75 years or those receiving warfarin who have good control. There were limited data on harms. 

Mechanism of action

Rivaroxaban is an oxazolidinone derivative optimized for inhibiting both free Factor Xa and Factor Xa bound in the prothrombinase complex. It is a highly selective direct Factor Xa inhibitor with oral bioavailability and rapid onset of action. Inhibition of Factor Xa interrupts the intrinsic and extrinsic pathway of the blood coagulation cascade, inhibiting both thrombin formation and development of thrombi. Rivaroxaban does not inhibit thrombin (activated Factor II), and no effects on platelets have been demonstrated.

Chemistry

Chemical structures of linezolid(top) and rivaroxaban (bottom). The shared structure is shown in blue.

Rivaroxaban bears a striking structural similarity to the antibiotic linezolid: both medicine share the same oxazolidinone-derived core structure. Accordingly, rivaroxaban was studied for any possible antimicrobial effects and for the possibility of mitochondrial toxicity, which is a known complication of long-term linezolid use. Studies found that neither rivaroxaban nor its metabolites have any antibiotic effect against Gram-positive bacteria. As for mitochondrial toxicity, in vitro studies found the risk to be low