Rivaroxaban was first discovered in 2008 and developed by Janssen Pharmaceutica and Bayer HealthCare. The drug received FDA approval in 2011 to reduce the risk of stroke and blood clots in patients with non-valvular atrial fibrillation. Rivaroxaban was found to be as safe and effective as warfarin, another anticoagulant, for this purpose. However, unlike warfarin, rivaroxaban does not require frequent monitoring with blood tests.
Early clinical trials also showed benefits of rivaroxabancompared to enoxaparin for treatment and prevention of deep vein thrombosis and pulmonary embolism. This led to the drug being additionally approved for these indications in 2012. Further approvals for other uses in clotting disorders followed based on positive results from large randomized controlled trials.
Mechanism of Action and Pharmacokinetics
Rivaroxaban works by selectively inhibiting Factor Xa in the coagulation cascade. Factor Xa plays a central role in the formation of blood clots. By blocking this factor, rivaroxaban prevents thrombin generation and subsequent clot formation.
When orally administered, rivaroxaban is rapidly absorbed, with maximum plasma concentrations achieved 2-4 hours posting. It has linear pharmacokinetics with dose-dependent anticoagulant activity. Rivaroxaban has a half-life of 5-9 hours in healthy individuals allowing for once or twice daily dosing. It is metabolized both by cytochrome P450 3A4 enzymes in the liver and by CYP-independent pathways.
About one third is eliminated renally with the remainder eliminated via the feces. Age, renal or hepatic impairment can increase drug exposure requiring dose adjustment. Food intake does not significantly alter rivaroxaban absorption. Due to its predictable pharmacokinetics, rivaroxaban does not require routine coagulation monitoring.
Clinical Trials and Efficacy Data
The ROCKET AF trial involving over 14,000 patients established rivaroxaban non-inferiority to warfarin in reducing stroke/systemic embolism in non-valvular atrial fibrillation. Major bleeds were similar between both drugs while intracranial bleeds were lower with rivaroxaban.
In venous thromboembolism treatment, EINSTEIN-DVT and EINSTEIN-PE trials proved rivaroxaban non-inferior to enoxaparin/vitamin K antagonist therapy. Rates of recurrent venous thromboembolism or death were lower with rivaroxaban.
The ATLAS ACS 2-TIMI 51 trial investigated rivaroxaban in addition to antiplatelet therapy post-acute coronary syndrome. It showed an 18% relative risk reduction in cardiovascular death, heart attacks or strokes compared to placebo without a significant increase in bleeding risk.
Commercial Success and Market Share Gains
Based on the robust clinical evidence, rivaroxaban has captured a significant share of the NOAC anticoagulant market since its launch. It is one of the leading oral anticoagulants prescribed for stroke prevention in non-valvular atrial fibrillation globally.
In 2020 alone, worldwide sales of rivaroxabantouched billion according to its manufacturers. In the US market, it currently commands over 30% of new prescriptions for non-vitamin K oral anticoagulants. Key factors driving uptake of this easy to use drug include once or twice daily dosing without monitoring requirements compared to warfarin.
Rivaroxaban is also cost effective for treating DVT/PE with longer term cost savings from lower re-hospitalization rates. With continued expansion into new indications, analysts project sales growth of 7-10% annually through 2026. This class leading oral blood thinner has changed treatment paradigms in clotting disorders.
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Roger Joined: September 27th, 2022 Articles Posted: 960
