FDA Approves New Dosing for Rivaroxaban to Reduce the Continued Risk of Venous Thromboembolism

Phase 3 study demonstrated 10-mg dose reduced risk of recurrent VTE by up to 74%

The FDA has approved the 10-mg once-daily dosing of rivaroxaban (Xarelto, Janssen) for reducing the continued risk for recurrent venous thromboembolism (VTE) after patients complete at least six months of initial anticoagulation therapy. This approval follows an FDA priority review and is based on data from the Einstein Choice trial, the only clinical study to find that a factor Xa inhibitor demonstrates superior efficacy in reducing the continued risk of recurrent VTE and with major bleeding rates similar to aspirin.

VTE includes deep vein thrombosis (DVT), a blood clot in a deep vein (often the legs), and pulmonary embolism (PE), a clot that travels to the lung. It is the third most common cause of cardiovascular death worldwide after heart attack and stroke.

With this approval, the rivaroxaban prescribing information will be amended to provide instructions for physicians to begin patient treatment with 15 mg, dosed twice daily, for the first 21 days after a VTE occurrence. On day 22 through at least day 180, the daily dose decreases to 20 mg once daily. After at least 180 days (six months), physicians can prescribe 10 mg once daily for patients at continued risk for DVT and/or PE.

"If anticoagulation therapy is stopped, up to 20% of patients will have a recurrent VTE within three years. To prevent this, physicians have long debated how best to extend anticoagulant use beyond the initial treatment window," said Jeffrey Weitz, MD, FRCP(C), FACP, Professor in the Departments of Medicine and Biochemistry and Biomedical Sciences at McMaster University, and Executive Director of the Thrombosis and Atherosclerosis Research Institute. "The FDA’s approval of the 10-mg dose of Xarelto for preventing recurrent VTE, along with clinical evidence confirming the superiority of Xarelto over aspirin for extended VTE prevention, means we can finally put this debate to rest."

The FDA’s approval of the 10-mg once-daily dose was based on the Einstein Choice study results, which evaluated patients with VTE who were already treated with six to 12 months of initial anticoagulation therapy and then received rivaroxaban 10 mg once daily, rivaroxaban 20 mg once daily, or aspirin 100 mg once daily for up to an additional 12 months of treatment. Patients taking either rivaroxaban dose had significantly fewer recurrent VTE episodes compared to those taking aspirin. Specifically, rivaroxaban 10 mg reduced the risk of recurrent VTE by 74% and rivaroxaban 20 mg by 66%. All three treatment groups had low rates of major bleeding (0.4% with rivaroxaban 10 mg, 0.5% with rivaroxaban 20 mg, and 0.3% with aspirin).

Source: Janssen; October 30, 2017.