FDA Gives Rivaroxaban Another VTE-Related Indication

Rivaroxaban (Xarelto; Bayer/Janssen) has gained an additional indication, this time for venous thromboembolism (VTE) prophylaxis in acutely ill hospitalized patients at increased risk for thromboembolic complications but not at high risk of bleeding, Janssen announced Monday.

With the expanded indication, granted by the US Food and Drug Administration late last week, rivaroxaban, at a dose of 10 mg once daily, can be started during the hospital stay and continued for 31 to 39 days.

In this setting, rivaroxaban should not be used in patients with a creatinine clearance below 30 mL/min or in those at high bleeding risk. The following factors are associated with an increased bleeding risk, according to drug’s updated label:

• History of bronchiectasis, pulmonary cavitation, or pulmonary hemorrhage
• Active cancer
• Active gastroduodenal ulcer in the last 3 months
• History of bleeding in the last 3 months
• Use of dual antiplatelet therapy

“Xarelto is not for use for primary VTE prophylaxis in these hospitalized, acutely ill medical patients at high risk of bleeding,” the label states.

Rivaroxaban was evaluated in this setting in two phase III trials. In MAGELLAN, use of rivaroxaban for 31 to 39 days reduced the risk of a composite of asymptomatic proximal deep venous thrombosis (DVT) in a lower extremity, symptomatic proximal or distal DVT in a lower extremity, symptomatic nonfatal pulmonary embolism, or VTE-related death, compared with 6 to 14 days of enoxaparin followed by placebo. Greater benefits were seen in the subgroup of patients without a high bleeding risk. Rivaroxaban was noninferior to enoxaparin through the first 10 days.

In the later MARINER trial, 45 days of rivaroxaban did not reduce the risk of a composite of symptomatic VTE or VTE-related death compared with placebo, although there were some hints of benefit seen in exploratory analyses of secondary endpoints.

“While Xarelto did not reduce the composite endpoint of VTE and VTE-related death, it did significantly reduce symptomatic VTE with consistent and favorable safety, reinforcing the positive benefit-risk profile of Xarelto,” Janssen stated in a press release.

Rivaroxaban already has several other FDA-approved indications. These include prevention of stroke and systemic embolism in A-fib, treatment of DVT and pulmonary embolism, prevention of recurrent DVT or PE, DVT prophylaxis in patients undergoing knee or hip replacement surgery, and (in combination with aspirin) prevention of major CV events in patients with chronic CAD or PAD.