Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions

Rivaroxaban represents a selective direct inhibitor of activated coagulation factor X (FXa) having peroral bioavailability and prompt onset of action.

The absorbtion of rivaroxaban is quick, reaching maximum plasma concentration 2-4 hours following its administration. Peroral bioavailability is high (80-100 %) and pharmacokinetic variability is considered to be moderate (coefficient of variation 30-40 %). This review discusses the properties, drug interactions, pharmacokinetics and clinical indications of rivaroxaban.

Dosing regimen of rivaroxaban was derived from pharmacologic data of the development program aimed to gain strong antithrombotic drug and balance between efficacy and risk of bleeding in patients. Results of doseranging trials, pharmacokinetic models and randomised studies of phase III advocate the use of such schemes in everyday practice.

The drug has been manufactured to fulfill clinical requirements in a variety of indications in adults: prophylaxis of venous thromboembolism (VTE) following elective knee or hip replacement surgical intervention, therapy and secondary prophylaxis of VTE, prophylaxis of ischemic stroke and embolism in individuals diagnosed with nonvalvular atrial fibrillation (NVAF) with risky characteristics, and in Europe the prophylaxis of atherothrombotic episodes following an acute coronary syndrome in subjects with increased levels of cardiac biomarkers.

Rivaroxaban may offer benefit in many clinical situations. In comparison with low molecular weight heparin and fondaparinux requiring subcutaneous way of administration, and with vitamin K antagonists (VKAs), which require regular monitoring of international normalized ratio, rivaroxaban is relatively easy to use. However, adjustments of dose are needed in individuals with impaired renal functions.