Herb-Drug Interaction between Echinacea purpurea and Darunavir-Ritonavir in HIV-Infected Patients

Abstract

The aim of this open-label, fixed-sequence study was to investigate the potential of Echinacea purpurea, a commonly used botanical supplement, to interact with the boosted protease inhibitor darunavir-ritonavir. Fifteen HIV-infected patients receiving antiretroviral therapy including darunavir-ritonavir (600/100 mg twice daily) for at least 4 weeks were included. E. purpurea root extract capsules were added to the antiretroviral treatment (500 mg every 6 h) from days 1 to 14. Darunavir concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, and 12 h after a morning dose of darunavir-ritonavir on days 0 (darunavir-ritonavir) and 14 (darunavir-ritonavir plus echinacea). Individual darunavir pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 with the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 49 (range, 43 to 67) years, and the body mass index was 24.2 (range, 18.7 to 27.5) kg/m 2 . Echinacea was well tolerated, and all participants completed the study. The GMR for darunavir coadministered with echinacea relative to that for darunavir alone was 0.84 (90% CI, 0.63-1.12) for the concentration at the end of the dosing interval, 0.90 (90% CI, 0.74-1.10) for the area under the concentration-time curve from 0 to 12 h, and 0.98 (90% CI, 0.82-1.16) for the maximum concentration. In summary, coadministration of E. purpurea with darunavirritonavir was safe and well tolerated. Individual patients did show a decrease in darunavir concentrations, although this did not affect the overall darunavir or ritonavir pharmacokinetics. Although no dose adjustment is required, monitoring darunavir concentrations on an individual basis may give reassurance in this setting.

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance

“…Similar results were obtained in HIV-infected patients where Echinacea treatment, every 6 h for 28 days did not show an effect on C max and AUC (0-24) of etravirine (ClinicalTrials.gov:NCT01347658) [141], darunavir and ritonavir (ClinicalTrials.gov:NCT01046890) [142]. The limited number of patients included in the studies requires such results to be taken with great caution also in light of the fact that, after Echinacea treatment, individual patients did show a decrease in darunavir concentration at the end of the dosing interval (40%) and area under the time-concentration curve (30%) [142]. Moreover, additional experiments are clearly necessary to clarify whether or not Echinacea may inhibit intestinal CYP3A4 and induce hepatic CYP3A4 along with the identification of the active compounds and the underlying mechanisms.…”

“…More recently, Goey and colleagues [140] reported no changes in docetaxel AUC (0-∞) , t 1/2 and C max pre-and post-infusion values in cancer patients after treatment with Echinaforce ® three times daily for fourteen days [140]. Similar results were obtained in HIV-infected patients where Echinacea treatment, every 6 h for 28 days did not show an effect on C max and AUC (0-24) of etravirine (ClinicalTrials.gov:NCT01347658) [141], darunavir and ritonavir (ClinicalTrials.gov:NCT01046890) [142]. The limited number of patients included in the studies requires such results to be taken with great caution also in light of the fact that, after Echinacea treatment, individual patients did show a decrease in darunavir concentration at the end of the dosing interval (40%) and area under the time-concentration curve (30%) [142].…”

Drug–drug interactions during antiviral therapy for chronic hepatitis C

“…99 In vitro, Echinacea , garlic, ginkgo biloba, ginseng, silymarin, and St John's wort have been shown to inhibit or induce enzymes or transporters involved in the metabolism or disposition of boceprevir and telaprevir. 99 In vivo , Echinacea 100,101 and silymarin 102,103 do not substantially alter HIV protease inhibitor exposures, but garlic and ginseng reduce CYP3A substrates by 44–51%. 104,105 Reductions of a similar magnitude could result in subtherapeutic boceprevir or telaprevir exposures, thus use of garlic and ginseng supplements should be avoided.…”

Interactions between Herbs and Conventional Drugs: Overview of the Clinical Data

“…Finally, a recent clinical trial showed that E. purpurea root extract did not affect the overall darunavir or ritonavir (a combination of protease inhibitors) pharmacokinetics in HIV patients [51]. Protease inhibitors are mainly metabolized by CYP3A4 and are P-glycoprotein substrates.…”