Bioequivalence of two different formulations of rivaroxaban film-coated tablet

Abstract

Aims: Studies aimed to evaluate the bioequivalence of 10 mg and 20 mg of Rivaroxaban film-coated tablets developed by Gedeon Richter Plc. (Hungary) compared to the reference product Xarelto^® (Bayer AG, Germany).

Methods: Two randomized, open-label, two-period, two-sequence crossover studies were conducted in healthy male subjects. Study A assessed the 10 mg dose under fasting conditions (n=42), while Study B evaluated the 20 mg dose under fed conditions (n=30). Pharmacokinetic parameters including AUCₜ, AUC_inf, and Cₘₐₓ were determined using validated LC-MS/MS methods. Bioequivalence was concluded if the 90% confidence intervals (CIs) for the test/reference ratios of these parameters fell within the 80.00–125.00% range.

Results: In Study A, the geometric mean ratios (GMRs) for AUCₜ and Cₘₐₓ were 97.32% and 90.39%. In Study B, the GMRs for AUCₜ and Cₘₐₓ were 98.35% and 95.98%.  All 90% CIs were within the predefined bioequivalence limits. Both formulations were well tolerated. Only mild and well-known treatment-emergent adverse events (TEAEs) were reported, without any treatment discontinuation.

Conclusions: The 10 mg and 20 mg Rivaroxaban formulations developed by Gedeon Richter Plc. are bioequivalent to Xarelto^® and are safe and well tolerated. These results support their use as clinically interchangeable alternatives to the reference product.