A comparative in vitro study of the coagulation effects of branded versus generic preparations of rivaroxaban

Abstract

During the last few years, several generic versions of rivaroxaban were approved to be used interchangeably with their branded equivalent Xarelto®. However, there were no previous studies in the literature that directly compared the anticoagulant effects of branded and generic preparations of rivaroxaban on different coagulation assays. The main aim of this study was to compare the in vitro anticoagulant effects of Xarelto® with two generic versions (Rivaroxaban Sandoz® and Rivarolto®) on a panel of coagulation assays. The study was performed by pooling normal plasma from six healthy donors and spiking it with different concentrations of the branded type and the two generic versions of rivaroxaban (concentration range 50 - 750 ng/ml). The concentrations were checked by testing with Chromogenic anti-Xa and adjusted accordingly. High-performance liquid chromatography was performed for a more accurate measurement of each concentration. The concentrations were tested on several coagulation assays: Prothrombin time (PT), activated Partial Thromboplastin time (aPTT), Thrombin time (TT), Clauss Fibrinogen, PT-derived Fibrinogen (PT-Fg), Diluted Russell’s Viper Venom Test (dRVVT), One-stage Factor VII, One-stage and chromogenic Factors VIII and Factor IX, Thromboelastography (TEG). The Pearson’s correlation test was utilized to check for correlation between the concentrations of the three different rivaroxaban preparations and the selected assays. The One-Way ANOVA test was utilized to identify any variability in their action on the selected assays. There was a positive correlation between the concentrations of the three preparations of rivaroxaban and PT, aPTT and dRVVT screen and confirm and PT-Fg. There was a negative correlation between the concentrations of the three preparations and the one-stage and chromogenic factor assays. The TT and Clauss Fibrinogen did not significantly correlate with any of the preparations. The TEG parameters produced conflicting correlation results due to a high intra-assay variability. No significant difference in the anticoagulant effect of the three rivaroxaban formulations was identified. This study showed that the generic versions of rivaroxaban do not exert any different in vitro anticoagulant effect from Xarelto® on the panel of coagulation assays.