Single and repeated doses of Ginkgo biloba extract EGb 761^®​ do not affect pharmacokinetics and pharmacodynamics of rivaroxaban in healthy volunteers

Introduction From one interaction study of a Ginkgo extract and talinolol, a potential for interactions with the transporter P-Glycoprotein (P-gp), which is involved in the excretion of direct oral anticoagulants, was postulated [1].

Aim To investigate whether EGb 761^®​ alters the pharmacokinetics or pharmacodynamics of the most frequently prescribed DOAC, rivaroxaban, in healthy subjects.

Method A single-centre, two-period, fixed-sequence, drug-drug interaction trial was conducted. In period 1, a single dose of rivaroxaban was given alone. In period 2, single doses of rivaroxaban were given on the first and last of 8 days of EGb 761^®​ treatment. Plasma concentrations of rivaroxaban and anti-Factor Xa activity were measured until 48 hours after each rivaroxaban dose. Within-subject comparisons of pharmacokinetic and pharmacodynamic parameters between the two periods were performed.

Results Data from 41 healthy volunteers (25 males, 16 females), aged 21 to 70 years, were evaluable. Differences between the two periods in maximum plasma concentration (C_max) and area under the concentration-time curve (AUC_0–∞) of rivaroxaban as well as in maximum effect (E_max) and area under the effect curve (AUEC_0–48) were minimal and not statistically significant for both single dose and steady state EGb 761^®​ intake. All respective point estimates were close to 100%, and all 90% confidence intervals were within the prespecified range of 80% to 125%. No adverse events related to haemorrhages or clinically significant findings in haematology or coagulation parameters were observed.

Conclusion This indicates that EGb 761^®​ has only a low, if any, influence on P-gp and does not affect coagulation.

Publication History

Article published online:
13 June 2022

• References

• 1 HMPC Assessment report on Ginkgo biloba L., folium. EMA/HMPC/321095/2012