Rivaroxaban: A Novel, Oral, Direct Factor Xa Inhibitor

Abstract

Thromboembolic disorders such as deep vein thrombosis, pulmonary embolism, myocardial infarction, and stroke often result in long-term disability and/or mortality. The anticoagulants currently available have been effective in the treatment and prevention of these disorders; however, parenteral administration, variable pharmacokinetics and pharmacodynamics, drug and dietary interactions, and a requirement for frequent monitoring of efficacy and safety limit use of these drugs. Rivaroxaban is a novel, oral factor Xa inhibitor in clinical development for the treatment and prevention of thromboembolic diseases. Rivaroxaban is a small molecule directed at active sites, and the agent mechanistically differs from traditional anticoagulants, such as heparins and fondaparinux, in that its activity is independent of antithrombin and its ability to inhibit prothrombinase bound factor Xa. In addition, preclinical and clinical trial data indicate that rivaroxaban has predictable pharmacokinetics and pharmacodynamics, which are features that differentiate it from oral vitamin K antagonists. Phase II studies showed that rivaroxaban is safe and well tolerated across a wide range of doses. Furthermore, completed phase III studies demonstrated its efficacy in the prevention of venous thromboembolism after orthopedic surgery. Additional studies are now under way to evaluate the use of rivaroxaban in the treatment and prevention of other venous and arterial thromboembolic conditions.

Recurrent Subretinal Hemorrhage Associated With Rivaroxaban Anticoagulation

“…The half-life is 5 hours to 9 hours in healthy adults aged 20 years to 45 years and 11 hours to 19 hours in the elderly. 3 There is no widely supported antidote, although Rivaroxaban was approved by the FDA in 2011 for the prevention of blood clots after hip and knee replacement and for the prevention of stroke in patients with nonvalvular atrial fibrillation. In clinical trials, Wasserlauf et al 5 reported major bleeding as the most common side effect, occurring in up to 5.6% of patients.…”

Inhibition of Factor XII-Mediated Activation of Factor XI Provides Protection Against Experimental Acute Ischemic Stroke in Mice

“…In prevention, they have been shown to produce overall benefit by reducing the incidence of AIS in high-risk patient populations. However, despite relentless efforts and numerous clinical trials with antithrombotic agents and protocols to treat AIS, many approaches have failed primarily due to serious bleeding side effects, including hemorrhagic transformation and intracerebral hemorrhage, that outweigh the antithrombotic benefit [18-21, 25]. The most recent rational strategy to inhibit thrombogenesis in stroke involves identifying and targeting those prothrombotic functions of platelets and coagulation factors that are not essential for hemostasis.…”

The role of novel anticoagulants in the management of venous thromboembolism

“…38 In healthy individuals, rivaroxaban has an average half-life of 10 hours and is eliminated through both hepatic metabolism and renal excretion (33% and 66%, respectively). 38 As with other direct FXa inhibitors, rivaroxaban has been demonstrated to block both free and clot-bound FXa. 39, 40 Rivaroxaban may interact with both CYP3A4/5 and P-gp activators as well as inhibitors.…”

“…It was first approved for VTE prophylaxis in patients undergoing THR or TKR. 38,42,44,45,46,47 Based on results from the ROCKET AF trial, rivaroxaban was then approved for prevention of ischemic stroke and SE in patients with NVAF. 42,43 Finally, rivaroxaban received approval for treatment and then secondary prevention of acute DVT and PE.…”