Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence

Int J Clin Pharmacol Ther. 2004 Mar;42(3):139-48. doi: 10.5414/cpp42139.


St. John's Wort (SJW, Hypericum perforatum) is effective in mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, numerous reports indicate the possibility of important interactions with prescribed drugs. SJW has been shown to lower the plasma concentration (and/or the pharmacological effect) of a number of drugs including alprazolam, amitriptyline, cyclosporine, digoxin, fexofenadine, indinavir, irinotecan, methadone, nevirapine, simvastatin, tacrolimus, theophylline, warfarin, phenprocoumon and oral contraceptives. Induction of P-glycoprotein and/or cytochrome P450 (CYP) enzymes (particularly CYP 3A4) by SJW could explain such pharmacokinetic interactions. When combined with serotonin reuptake inhibitor, antidepressants (e.g. sertaline, paroxetine, nefazodone) or buspirone, SJW can cause serotonergic syndrome. SJW represents a herbal medicine with a high potential for drug interactions. Some of such interactions may have serious clinical consequences.

Publication types

  • Review

MeSH terms

  • Adult
  • Area Under Curve
  • Depressive Disorder / drug therapy
  • Female
  • Herb-Drug Interactions*
  • Humans
  • Hypericum / adverse effects*
  • Immunosuppressive Agents / pharmacokinetics*
  • Male
  • Middle Aged
  • Organ Transplantation
  • Phytotherapy / adverse effects*
  • Plant Extracts / adverse effects*
  • Plant Extracts / therapeutic use
  • Selective Serotonin Reuptake Inhibitors / therapeutic use


  • Immunosuppressive Agents
  • Plant Extracts
  • Serotonin Uptake Inhibitors