Single and Repeated Doses of EGb 761 do not Affect Pharmacokinetics or Pharmacodynamics of Rivaroxaban in Healthy Subjects.

The present drug-drug interaction study investigates whether single or repeated doses of 240 mg extract EGb 761 alter the pharmacokinetics or pharmacodynamics of rivaroxaban in healthy subjects. This was a single-centre, two-period, fixed-sequence trial. In Period 1, rivaroxaban was taken alone. In Period 2, rivaroxaban was given on the first and last of 8 days of EGb 761 treatment. Plasma concentrations of rivaroxaban and anti-Factor Xa activity were determined until 48 h after each rivaroxaban intake. The data of forty-one healthy subjects (25 males, 16 females) aged 21-70 years were evaluable. Geometric mean ratios (90% confidence intervals) for rivaroxaban administered concomitantly with a single or multiple doses of EGb 761 vs. rivaroxaban administered alone were 97.97 (91.78, 104.58) and 96.78 (90.67, 103.31) for maximum concentration (C), 98.55 (94.43, 102.84) and 97.82 (93.73, 102.08) for area under the concentration-time curve (AUC) of rivaroxaban in plasma (primary endpoints), 98.19 (92.00, 104.80) and 99.78 (93.43, 106.55) for maximum effect (E), 99.46 (93.63, 105.66) and 99.12 (93.25, 105.35) for area under the effect curve (AUEC). All 90% confidence intervals were within the prespecified range of 80%-125%. Neither adverse events related to haemorrhages nor clinically significant findings in haematology or coagulation parameters were observed. The treatments were safe and well-tolerated. Single and repeated doses of EGb 761® neither affect plasma concentrations of rivaroxaban nor anti-Factor Xa activity in healthy subjects.