From the Guidelines
Rivaroxaban works by inhibiting Factor Xa, a key enzyme in the blood clotting cascade, which prevents the formation of thrombin and subsequent clot development. This mechanism of action is supported by the most recent and highest quality study, which classifies rivaroxaban as an anti–factor Xa inhibitor 1. The study provides a summary of randomized trials of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin therapy in patients with atrial fibrillation, and rivaroxaban is listed as an anti–factor Xa inhibitor with a specific mechanism of action.
Key Characteristics of Rivaroxaban
- Metabolism: CYP3A4/5 1
- P-glycoprotein substrate: Yes 1
- Excretion: 66% renal, 28% feces 1
- Half-life: 5-9 h 1
- Renal dosing adjustment: CrCl >50 mL/min 20 mg daily, CrCl 15-50 mL/min 15 mg daily 1
Clinical Use of Rivaroxaban
- Atrial fibrillation: 20mg once daily with food 1
- Deep vein thrombosis or pulmonary embolism treatment: 15mg twice daily for 21 days followed by 20mg once daily
- DVT/PE prevention after surgery: 10mg once daily
- Rivaroxaban does not require routine blood monitoring and has fewer food interactions compared to warfarin, making it more convenient for patients 1
- However, it should be used cautiously in those with kidney problems, as it's primarily eliminated through the kidneys 1
- Common side effects include bleeding risk, which is its main concern 1
- Patients should be aware that rivaroxaban cannot be quickly reversed in emergency situations, though reversal agents are becoming available 1
- It's essential to take rivaroxaban exactly as prescribed and not to stop it suddenly without medical guidance, as this could increase clotting risk 1
From the FDA Drug Label
XARELTO is a selective inhibitor of FXa. It does not require a cofactor (such as Anti-thrombin III) for activity. Rivaroxaban inhibits free FXa and prothrombinase activity. Rivaroxaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, rivaroxaban decreases thrombin generation.
The mechanism of action of Rivaroxaban (Xarelto) is as a selective inhibitor of Factor Xa (FXa), which inhibits free FXa and prothrombinase activity, and indirectly inhibits platelet aggregation by decreasing thrombin generation 2.
- Key points:
- Inhibits FXa
- Inhibits prothrombinase activity
- No direct effect on platelet aggregation
- Indirectly inhibits platelet aggregation induced by thrombin
- Decreases thrombin generation
From the Research
Mechanism of Action of Rivaroxaban
- Rivaroxaban is an oral, direct Factor Xa inhibitor, which plays a crucial role in the coagulation cascade 3, 4, 5, 6, 7.
- By inhibiting Factor Xa, rivaroxaban prevents the conversion of prothrombin to thrombin, thereby reducing the formation of blood clots 3, 5.
- The drug has a rapid onset of action and predictable pharmacokinetic and pharmacodynamic properties, making it a convenient treatment option for patients with thromboembolic disorders 4, 6.
Pharmacokinetics and Pharmacodynamics
- Rivaroxaban has a short half-life and undergoes a dual mode of elimination, involving both hepatic and renal pathways 4.
- The drug is a substrate for P-glycoprotein and has a lower potential for drug interactions compared to warfarin 4.
- Population pharmacokinetic analyses have shown that rivaroxaban's pharmacokinetics are consistent and predictable across different doses and patient populations 3.
Clinical Applications
- Rivaroxaban is approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, as well as for the treatment and prevention of deep vein thrombosis and pulmonary embolism 4, 5, 6, 7.
- The drug has also been shown to be effective in preventing venous thromboembolism in patients undergoing elective hip or knee replacement surgery 5, 6, 7.