Interaction of herbal products with prescribed medications: A systematic review and meta-analysis

Pharmacol Res. 2019 Mar;141:397-408. doi: 10.1016/j.phrs.2019.01.028. Epub 2019 Jan 17.


Although several studies on pharmacokinetic and/or pharmacodynamic herb-drug interactions (HDI) have been conducted in healthy volunteers, there is large uncertainty on the validity of these studies. A qualitative review and a meta-analysis were performed to establish the clinical evidence of these interaction studies. Out of 4026 screened abstracts, 32 studies were included into the qualitative analysis. The meta-analysis was performed on eleven additional studies. St. John's wort (SJW) significantly decreased the AUC (p < 0.0001) and clearance (p = 0.007) of midazolam. Further subgroup analysis identified age to affect Cmax of midazolam (p < 0.01) in the presence of SJW. Echinacea purpurea (EP) significantly increased the clearance of midazolam (p = 0.01). Evidence of publication bias (p > 0.001) was shown on the effect of the herbal products o half-life of midazolam. Green tea (GT) showed significant 85% decrease in plasma concentration of nadolol. The study findings suggest that GT, SJW and EP perpetuate significant interactions with prescribed medications via CYP3A4 or OATP1A2. Our studies show that meta-analyses are important in the area of natural products to provide necessary information on their use in overall medication plans in order to avoid unintended interactions.

Keywords: Cytochrome P450; Drug transporters; Herbal products; Herb–drug interactions; Prescribed medications.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Echinacea / chemistry
  • Herb-Drug Interactions*
  • Humans
  • Hypericum / chemistry
  • Hypnotics and Sedatives / metabolism
  • Hypnotics and Sedatives / pharmacokinetics
  • Midazolam / metabolism
  • Midazolam / pharmacokinetics
  • Oximes / metabolism
  • Oximes / pharmacokinetics
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Tea / chemistry


  • Hypnotics and Sedatives
  • Oximes
  • Plant Preparations
  • Tea
  • Cytochrome P-450 Enzyme System
  • Midazolam
  • nadoxolol