Clopidogrel performed with rivaroxaban and different antihemostatic agents. Coadministration of enoxaparin with rivaroxaban resulted in an additive FXa inhibition, as measured by anti FXa assay. The effect of bleeding time prolongation during the coadministration of clopidogrel seems to be more pronounced. The use of low doses of rivaroxaban and warfarin confirmed that no overadditive effects were observed at the doses investigated.10 In the case of an overdose of rivaroxaban, recombinant activated factor VII and prothrombin complex concentrate were used in rabbit model to reverse the anticoagulant chemical catalogs effect.11 This study showed rFVIIa and PCC decreased aPTT and clotting time, however, these agents did not affect rivaroxaban induced bleeding. On the contrary, a randomized controlled trial in healthy volunteers demonstrated that a single bolus of PCC effectively normalized the PT after the administration of 40 mg rivaroxaban daily.
Clinical Development Venous thromboembolism prophylaxis after total hip or knee arthroplasty. Rivaroxaban is currently approved for the phospholipases prevention of VTE after elective hip and knee arthroplasty. Result from phase II trials that assessed approximately 2900 patients on different strengths of rivaroxaban revealed that rivaroxaban 10 mg once daily had the optimum balance between efficacy and safety, compared to the standard therapy of 40 mg enoxaparin once daily.13 Rivaroxaban was further investigated in a series of 4 phase III trials that accumulatively recruited more than 12 500 patients. The studies of patients who underwent knee replacement were done in RECORD 114 and RECORD 2.15 These studies demonstrated that 10 mg of rivaroxaban was superior to a once daily dose of 40 mg enoxaparin for the prevention of VTE and all cause mortality. Meanwhile, the RECORD 316 and RECORD 417 trials were conducted in patients who underwent hip replacement. These trials showed that 10 mg of rivaroxaban was superior to enoxaparin in both 40 mg daily and 30 mg twice daily for the same capecitabine outcomes. In all 4 trials, there were no clinically significant differences in the rates of major bleeding or liver enzyme dysfunctions between the 2 regimens. Overall, rivaroxaban showed a good safety profile, including major bleeding risk and hepatic dysfunction.
In addition, there is no need for a routine coagulation monitoringand dose adjustment for any demographic variables. This is consistent with the preliminary marker results from pooled subgroup analysis.18 Currently, rivaroxaban was approved in the United States, Europe, and Canada for the prevention of venous thrombosis in hip and knee arthroplasty.19 Treatment of venous thromboembolism. The efficacy and safety of rivaroxaban in the treatment of VTE, as a replacement of warfarin, were assessed in 2 phase II studies, ODIXa DVT20 and EINSTEIN DVT.21 These studies suggested that rivaroxaban had similar properties in both efficacy and safety profiles compared with standard regimen. EINSTEIN DVT is a double blind, randomized trial compared oral rivaroxaban 20 mg once daily with standard treatment of deep venous thrombosis with subcutaneous enoxaparin followed by a vitamin K antagonist over a year of follow up period. The first VTE events occurred in 2.1% of rivaroxaban arm, compared with 3.0% of those in enoxapari.