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

Abstract

The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement Echinacea purpurea to interact with etravirine, a nonnucleoside reverse transcriptase inhibitor of HIV. Fifteen HIV-infected patients receiving antiretroviral therapy with etravirine (400 mg once daily) for at least 4 weeks were included. E. purpurea root/extract-containing capsules were added to the antiretroviral treatment (500 mg every 8 h) for 14 days. Etravirine concentrations in plasma were determined by high-performance liquid chromatography immediately before and 1, 2, 4, 6, 8, 10, 12, and 24 h after a morning dose of etravirine on day 0 and etravirine plus E. purpurea on day 14. Individual etravirine pharmacokinetic parameters were calculated by noncompartmental analysis and compared between days 0 and 14 by means of the geometric mean ratio (GMR) and its 90% confidence interval (CI). The median age was 46 years (interquartile range, 41 to 50), and the median body weight was 76 kg (interquartile range, 68 to 92). Echinacea was well tolerated, and all participants completed the study. The GMR for etravirine coadministered with E. purpurea relative to etravirine alone was 1.07 (90% CI, 0.81 to 1.42) for the maximum concentration, 1.04 (90% CI, 0.79 to 1.38) for the area under the concentration-time curve from 0 to 24 h, and 1.04 (90% CI, 0.74 to 1.44) for the concentration at the end of the dosing interval. In conclusion, the coadministration of E. purpurea with etravirine was safe and well tolerated in HIV-infected patients; our data suggest that no dose adjustment for etravirine is necessary.

Randomised Study to Assess the Efficacy and Safety of Once-Daily Etravirine-Based Regimen as a Switching Strategy in HIV-Infected Patients Receiving a Protease Inhibitor–Containing Regimen. Etraswitch Study

“…This new formulation will facilitate dosing and, consequently, patient acceptance and satisfaction. In addition, plasma concentrations of etravirine, administered once daily dissolved in water, were in the same range to those observed in subjects receiving undispersed etravirine tablets [11]–[14]. As well, all patients showed etravirine concentrations above the protein-binding adjusted 50% effective concentration 4 ng/mL.…”

A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

“…The results of the study were not clinically significant [109]. In a similar study, the use of echinacea did not effect etravirine concentrations in HIVinfected individuals [110].…”

Review and Assessment of Medicinal Safety Data of Orally Used Echinacea Preparations

“…Similar to lopinavir studied by Penzak et al, no significant interaction has been found with darunavir [19]. Also no significant treatment effects were observed for any of the primary pharmacokinetic parameters after administration of etravirine with or without E. purpurea [20]. Already in 2007, Raner et al evaluated the potential of 11 isolated alkamides and a 33% and 95 % ethanolic E. purpurea root extract to inhibit cytochrome P450 2E1 in human liver microsomes and from an in vitro expression system.…”

“…A number of in vitro and in vivo studies suggest a potential for herb-drug interaction between different uncharacterized Echinacea extracts and the cytochrome P450 family of drug metabolizing enzymes (CYP 3A4, 2D6, 1 A2 and 2C9) [14][15][16][17]. But only the recently published pharmacokinetic drug interaction studies determined the influence of chemically characterized Echinacea preparations on CYP3A and CYP2D6, with four conducted in human [18][19][20][21] and seven in vitro studies [22][23][24][25][26][27].…”

“…With the in vivo studies published no significant inhibitions of human CYP2D6 and CYP3A4 isoforms have been found after the application of standardized E. purpurea preparations (softgel capsules with 267 mg, 3 times daily or fresh plant liquid extract again in softgel capsules with 500 mg, 3 times daily) [18,21]. No significant interaction has been found with etravirine, darunavir, and lopinavir-ritonavir, which undergoes extensive metabolism by the hepatic CYP3A4 isoform [19][20][21]. Only a cautious conclusion can been drawn that Echinacea alkamides inhibit CYP2E1 and CY-P3A4 in human liver microsomes or enzyme substrates (supersome assay) [27].…”