Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans.

Scholz, Irene; Liakoni, Evangelia; Hammann, Felix; Grafinger, Katharina Elisabeth; Duthaler, Urs; Nagler, Michael; Krähenbühl, Stephan; Haschke, Manuel (2020). Effects of Hypericum perforatum (St John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans. (In Press). British journal of clinical pharmacology Wiley-Blackwell 10.1111/bcp.14553

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AIMS

To investigate the influence of a cytochrome P450 CYP3A4 and efflux transporter P-glycoprotein (P-gp) inducing Hypericum perforatum extract on the pharmacokinetics and pharmacodynamics of rivaroxaban.

METHODS

Open-label, nonrandomized, sequential treatment interaction study. Following CYP3A4 and P-gp phenotyping using low-dose midazolam and fexofenadine, 12 healthy volunteers received a single oral dose of 20 mg rivaroxaban and rivaroxaban plasma concentrations and inhibition of the activated coagulation factor X (factor Xa) activity were measured prior to and up to 48 h postdosing. The procedures were repeated after 2 weeks' treatment with the H. perforatum extract.

RESULTS

The geometric mean ratios for the area under the concentration-time curve and Cmax of rivaroxaban after/before induction with the H. perforatum extract were 0.76 (90% confidence interval [CI] 0.70, 0.82) and 0.86 (90% CI 0.76, 0.97), respectively. Inhibition of factor Xa activity was reduced with a geometric mean area under the effect-time curve ratio after/before induction of 0.80 (90% CI 0.71, 0.89). No clinically significant differences were found regarding Tmax (median 1.5 vs 1 h, P = .26) and terminal elimination half-life (mean 10.6 vs 10.8 h, P = .93) of rivaroxaban. The H. perforatum extract significantly induced CYP3A4 and P-gp activity, as evidenced by phenotyping.

CONCLUSION

The CYP3A4/P-gp inducing H. perforatum extract caused a decrease of rivaroxaban exposure with a proportional decrease of the pharmacodynamic effect. Although the data do not justify a contraindication for the combination or a systematic adjustment of rivaroxaban dosage, avoidance of the combination or laboratory monitoring should be considered in patients taking hyperforin-containing H. perforatum extracts with rivaroxaban.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

UniBE Contributor:

Scholz, Irene; Liakoni, Evangelia; Hammann, Felix; Grafinger, Katharina; Nagler, Michael; Krähenbühl-Melcher, Stephan and Haschke, Manuel Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0306-5251

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Christine Baumgartner

Date Deposited:

26 Nov 2020 07:27

Last Modified:

26 Nov 2020 07:27

Publisher DOI:

10.1111/bcp.14553

PubMed ID:

32959922

Uncontrolled Keywords:

CYP3A4 Hypericum perforatum P-glycoprotein St John's wort cytochrome P450 drug interaction phenotyping rivaroxaban

BORIS DOI:

10.7892/boris.147679

URI:

https://boris.unibe.ch/id/eprint/147679

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