St John's wort (Hypericum perforatum): drug interactions and clinical outcomes

Br J Clin Pharmacol. 2002 Oct;54(4):349-56. doi: 10.1046/j.1365-2125.2002.01683.x.


Aims: The aim of this work is to identify the medicines which interact with the herbal remedy St John's wort (SJW), and the mechanisms responsible.

Methods: A systematic review of all the available evidence, including worldwide published literature and spontaneous case reports provided by healthcare professionals and regulatory authorities within Europe has been undertaken.

Results: A number of clinically significant interactions have been identified with prescribed medicines including warfarin, phenprocoumon, cyclosporin, HIV protease inhibitors, theophylline, digoxin and oral contraceptives resulting in a decrease in concentration or effect of the medicines. These interactions are probably due to the induction of cytochrome P450 isoenzymes CYP3A4, CYP2C9, CYP1A2 and the transport protein P-glycoprotein by constituent(s) in SJW. The degree of induction is unpredictable due to factors such as the variable quality and quantity of constituent(s) in SJW preparations. In addition, possible pharmacodynamic interactions with selective serotonin re-uptake inhibitors and serotonin (5-HT(1d)) receptor-agonists such as triptans used to treat migraine were identified. These interactions are associated with an increased risk of adverse reactions.

Conclusions: In Sweden and the UK the potential risks to patients were judged to be significant and therefore information about the interactions was provided to health care professionals and patients. The product information of the licensed medicines involved has been amended to reflect these newly identified interactions and SJW preparations have been voluntarily labelled with appropriate warnings.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Contraceptives, Oral / metabolism
  • Cyclosporine / metabolism
  • Digoxin / metabolism
  • Drug Interactions*
  • HIV Protease Inhibitors / metabolism
  • Herb-Drug Interactions
  • Humans
  • Hypericum / adverse effects
  • Hypericum / metabolism*
  • Plant Extracts / adverse effects
  • Plant Extracts / metabolism*
  • Selective Serotonin Reuptake Inhibitors / metabolism
  • Theophylline / metabolism
  • Warfarin / metabolism


  • Contraceptives, Oral
  • HIV Protease Inhibitors
  • Plant Extracts
  • Serotonin Uptake Inhibitors
  • Warfarin
  • Digoxin
  • Cyclosporine
  • Theophylline