September 1, 2014Open Access
Clinical Use of Rivaroxaban: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Regimens in Different Indications
Key Result
Rivaroxaban has predictable pharmacokinetic and pharmacodynamic profiles that support specific fixed-dosing regimens for the prevention and treatment of various thromboembolic disorders.
Structured PICO
P
Population
Patients with thromboembolic disorders (including non-valvular atrial fibrillation, venous thromboembolism, acute coronary syndrome, and patients undergoing hip or knee replacement surgery) and healthy subjects in pharmacokinetic studies.
I
Intervention
Rivaroxaban at various dosing regimens (e.g., 10 mg once daily, 20 mg once daily, 15 mg twice daily, 2.5 mg twice daily) depending on the clinical indication.
C
Comparator
Traditional anticoagulants (e.g., enoxaparin, vitamin K antagonists) or standard antiplatelet therapy, as reviewed from phase II and III trials.
This review outlines the pharmacokinetic and pharmacodynamic basis for the specific dosing regimens of rivaroxaban across various thromboembolic indications.
Limitations
- Drug accumulation in patients with renal dysfunction
- Lack of an antidote or standardized reversal strategy when life-threatening bleeding is encountered
- Difficulties in quantifying the degree of anticoagulation with commonly available assays in emergency situations
Abstract
Target-specific oral anticoagulants have become increasingly available as alternatives to traditional agents for the management of a number of thromboembolic disorders. To date, the direct Factor Xa inhibitor rivaroxaban is the most widely approved of the new agents. The dosing of rivaroxaban varies and adheres to specific schedules in each of the clinical settings in which it has been investigated. These regimens were devised based on the results of phase II dose-finding studies and/or pharmacokinetic modeling, and were demonstrated to be successful in randomized, phase III studies. In most cases, the pharmacodynamic profile of rivaroxaban permits once-daily dosing. A once-daily dose is indicated for the prevention of venous thromboembolism (VTE) in patients undergoing hip or knee replacement surgery, the long-term prevention of stroke in patients with non-valvular atrial fibrillation, and the long-term secondary prevention of recurrent VTE. Twice-daily dosing is required in the acute phase of treatment in patients with VTE and in the combination of rivaroxaban with standard single or dual antiplatelet therapy for secondary prevention after acute coronary syndrome events. This article reviews the empirical and clinical rationale supporting the dose regimens of rivaroxaban in each clinical setting.