Evaluation of bioequivalence between two rivaroxaban formulations – coated tablet 20 mg – administered under fasting and fed conditions in healthy volunteers

Abstract

Objective: The objective of the present study was to evaluate the bioequivalence between two formulations of rivaroxaban 20 mg coated tablet, the test formulation being manufactured by Sanofi Medley, Brazil and the reference formulation (Xarelto® ) commercialized by Bayer S/A. Methods: The studies were conducted in healthy volunteers of both sexes and the formulations were administered in a single dose, under fasting and fed conditions. Each study was conducted independently, both being open-label, randomized and with a seven-day interval (washout) between periods. The fasting study was carried out in four periods, with 48 volunteers, while the fed study was carried out in two periods, with 36 volunteers. Results: In the fasting administration, the ratio between the geometric mean of the test and reference formulation (T/R) of Cmax was 100.77%, with a 90% confidence interval (CI 90%) from 94.24% to 107.76%. For ASC0-t, the T/R ratio was 100.65%, with CI 90% from 96.13% to 105.39%. In the fed administration, T/R ratio of Cmax was 110.63%, with CI 90% from 102.39% to 119.54%. For ASC0-t, T/R ratio was 104.65%, with CI 90% from 98.44% to 109.12%. Conclusions: The test and reference formulations were considered statistically bioequivalent in both administration conditions, according to the criteria required by Brazilian National Health Surveillance Agency (Anvisa). The test formulation was registered in Anvisa and made available for commercialization, thus contributing to expanding the availability of treatment for thromboembolic diseases and reducing costs to the patients and to the Unified Health System.