Pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Echinacea and policosanol are commonly used herbal medicines which may be ingested by patients receiving warfarin. Echinacea has been implicated in interacting with drug metabolizing enzymes and policosanol has been shown to decrease platelet aggregation. The potential interaction of echinacea and policosanol with warfarin has not previously been investigated. WHAT THIS STUDY ADDS • Concomitant treatments with echinacea increased the apparent clearance of S‐warfarin but did not have a clinically significant effect on warfarin pharmacodynamics in healthy subjects. Policosanol did not significantly affect warfarin pharmacokinetics or pharmacodynamics. AIMS This study investigated the pharmacokinetic and pharmacodynamic interactions of echinacea and policosanol with warfarin in healthy subjects. METHODS This was an open‐label, randomized, three‐treatment, cross‐over, clinical trial in healthy male subjects (n= 12) of known CYP2C9 and VKORC1 genotype who received a single oral dose of warfarin alone or after 2 weeks of pre‐treatment with each herbal medicine at recommended doses. Pharmacodynamic (INR, platelet activity) and pharmacokinetic (warfarin enantiomer concentrations) end points were evaluated. RESULTS The apparent clearance of (S)‐warfarin (90% CI of ratio; 1.01, 1.18) was significantly higher during concomitant treatment with echinacea but this did not lead to a clinically significant change in INR (90% CI of AUC of INR; 0.91, 1.31). Policosanol did not significantly affect warfarin enantiomer pharmacokinetics or warfarin response. Neither echinacea nor policosanol had a significant effect on platelet aggregation after 2 weeks of pre‐treatment with the respective herbal medicines. CONCLUSION Echinacea significantly reduced plasma concentrations of S‐warfarin. However, neither echinacea nor policosanol significantly affected warfarin pharmacodynamics, platelet aggregation or baseline clotting status in healthy subjects.

In vitro inhibitory effects of herbal supplements on tamoxifen and irinotecan metabolism

“…Additionally, based on the measured IC50 values as percent of single dose, echinacea was observed to be a slightly more potent inhibitor of TAM metabolism as compared to ginseng. Previously, it has been shown that echinacea has had only moderate or no effect on conventional drugs in clinical settings [26][27][28][29], while the effects of ginseng have been reported to be even less [26,29,30]. In general, echinacea and ginseng are considered low risk for drug-herb interaction which is consistent with our data.…”

Interactions of commonly used dietary supplements with cardiovascular drugs: a systematic review

“…Evidence from one study for the combination of Echinacea and warfarin was inconclusive (grade: low) [97]. …”

“…Results of one study showed no clinically important but a statistically significant decrease (grade: insufficient) in S-warfarin AUC ∞, an increase in drug clearance and an apparent increase in volume of distribution (GMRs: 0.92 (90% CI 0.85, 0.99); 1.09 (90% CI 1.01, 1.18); and 1.09 (95% CI 1.03, 1.18), respectively) [97]. …”

Nutraceuticals with lipid-lowering activity: do they have any effect beyond cholesterol reduction?

“…The policosanol tolerability has also been tested in children [66]. Moreover, policosanols seem to have no interaction with warfarin [67].…”