Rivaroxaban: Practical Considerations for Ensuring Safety and Efficacy

Abstract

Rivaroxaban is the first agent available within a new class of anticoagulants called direct factor Xa inhibitors. Rivaroxaban is approved for use in the United States for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for the prevention of deep vein thrombosis in patients undergoing total hip replacement and total knee replacement, for the treatment of deep vein thrombosis and pulmonary embolism, and for the reduction in risk of recurrence of deep vein thrombosis and pulmonary embolism (with additional indications under review). Rivaroxaban dose and frequency of administration vary depending on the indication. As of result of predictable pharmacokinetics and pharmacodynamics, a fixed dose of rivaroxaban is administered without routine coagulation testing. Rivaroxaban has a short half-life, undergoes a dual mode of elimination (hepatic and renal), and is a substrate for P-glycoprotein. Rivaroxaban has a lower potential for drug interactions compared with warfarin. Despite the advantages of a once/day fixed-dose oral agent, in many clinical situations limited evidence is available to guide optimal management of rivaroxaban therapy. In this article, we review the available evidence and provide recommendations where possible for such situations including the desire to monitor the anticoagulation intensity, use in special patient populations, managing drug interactions, and transitioning across anticoagulant agents. Potential strategies for reversing rivaroxaban's anticoagulant effect are reviewed. Health systems will need to perform a systematic safety evaluation and ensure that numerous hospital policies related to anticoagulation are updated to include rivaroxaban. A comprehensive approach to education is needed for clinicians, patients, and technical support personnel involved in patient interactions to ensure safe use.

Bilateral Lung Transplantation in a Patient Receiving Rivaroxaban Anticoagulation

“…Cyclosporine, which the patient had received a few hours prior to the transplantation, also is an inhibitor of CYP3A4 and P-glycoprotein and could have further increased the plasma concentration. 9 Due to these drug interactions the authors had to consider a decreased rivaroxaban metabolism resulting in an increased bleeding risk. This was one of the reasons why they measured the anti Xa activity preoperatively (Table 1).…”

Treatment of acute portal vein thrombosis by nontraditional anticoagulation

“…In conclusion, oral rivaroxaban is a very attractive therapeutic option for treatment of acute portal and mesenteric vein thrombosis in patients with compensated cirrhosis with preserved renal function. Predictable pharmacokinetics and pharmacodynamics allow a fixed dose of rivaroxaban without coagulation monitoring . It has a half‐life of up to 12 hours, its absorption is not affected by food, and one‐third of the drug is eliminated by the kidneys, while two‐thirds undergo metabolism in the liver .…”

“…Predictable pharmacokinetics and pharmacodynamics allow a fixed dose of rivaroxaban without coagulation monitoring . It has a half‐life of up to 12 hours, its absorption is not affected by food, and one‐third of the drug is eliminated by the kidneys, while two‐thirds undergo metabolism in the liver . Specific labeling restrictions for rivaroxaban regarding impaired hepatic function are based on both the Child‐Pugh classification and liver‐related exclusion criteria applied in pivotal trials .…”

“…It has a half‐life of up to 12 hours, its absorption is not affected by food, and one‐third of the drug is eliminated by the kidneys, while two‐thirds undergo metabolism in the liver . Specific labeling restrictions for rivaroxaban regarding impaired hepatic function are based on both the Child‐Pugh classification and liver‐related exclusion criteria applied in pivotal trials . It is currently contraindicated in patients with liver disease associated with coagulopathy, cirrhosis Child Class B or C, and clinically relevant bleeding risk .…”

“…Unfortunately, warfarin is limited by a narrow therapeutic window and a highly variable dose‐response requiring frequent dose adjustments and monitoring. Rivaroxaban is the first oral anticoagulant agent available within the class of factor Xa inhibitors and is approved for use in prevention or treatment of stroke, deep vein thrombosis, and pulmonary embolism . The efficacy of rivaroxaban for treatment of PVT was recently evaluated in a single patient with complete resolution in 4 weeks .…”