# St John's wort: an interaction to avoid

Source: https://onco.cc/technologies/st-johns-wort-interaction/  
OnCo record `st-johns-wort-interaction` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

St John's wort is a herbal antidepressant whose active ingredient hyperforin switches on the liver enzyme CYP3A4 and the P-glycoprotein pump, cutting blood levels of irinotecan's active metabolite by 42% and imatinib by about a third. It is contraindicated with most tyrosine kinase, CDK4/6 and PARP inhibitors, and its effect lasts two weeks after stopping.

## Summary

Hypericum perforatum induces CYP3A4 and P-glycoprotein through the pregnane X receptor. In a crossover pharmacokinetic study of five patients (Mathijssen et al., JNCI 2002), St John's wort reduced plasma levels of SN-38, the active metabolite of irinotecan, by 42 percent, enough to reduce efficacy; it lowers imatinib exposure by about a third and is contraindicated with most tyrosine kinase inhibitors, CDK4/6 inhibitors, PARP inhibitors, antiemetics such as aprepitant, and many antidepressants (serotonin syndrome). Its effect persists for two weeks after stopping. Depression in cancer patients should be treated with evidence-based psychotherapy or antidepressants chosen for their interaction profile. St John's wort is the clearest example of why oncology teams must ask about supplements at every visit.

## Fields

- Kind: Technology
- Status: established
- Last checked: 2026-09-10
- Tags: complementary; supportive-care; evidence:harm
- Principle: Hyperforin activates PXR, increasing transcription of CYP3A4 and ABCB1, which accelerates clearance of drugs that are substrates of these systems.
- Strengths: Interaction is well characterised and avoidable; Prompts systematic supplement reconciliation
- Limitations: Halves exposure to irinotecan and many oral anticancer drugs; Effect lasts two weeks after stopping; Serotonin syndrome with antidepressants

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Hypericum_perforatum
- Effects of St. John's wort on irinotecan metabolism (JNCI 2002): https://doi.org/10.1093/jnci/94.16.1247
- MSK About Herbs: St. John's wort: https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-johns-wort

## Connected records

- ideas: [An open supplement-drug interaction checker built into oncology prescribing](https://onco.cc/ideas/idea-moon-supplement-interaction-database/)
- fronts: [Supportive Care & Survivorship](https://onco.cc/fronts/supportive-care/)
- technologies: [Dietary supplements during cancer treatment: interactions and harms](https://onco.cc/technologies/dietary-supplements-treatment-interactions/), [Evidence-based integrative oncology](https://onco.cc/technologies/integrative-oncology/), [Psycho-oncology and distress screening](https://onco.cc/technologies/psycho-oncology/)
- drugs: [FOLFIRI (5-FU, leucovorin, irinotecan)](https://onco.cc/drugs/folfiri/), [Imatinib](https://onco.cc/drugs/imatinib/), [Irinotecan (and liposomal irinotecan)](https://onco.cc/drugs/irinotecan/), [Olaparib](https://onco.cc/drugs/olaparib/), [Palbociclib](https://onco.cc/drugs/palbociclib/)
- institutions: [Memorial Sloan Kettering Cancer Center](https://onco.cc/institutions/mskcc/)
- bottlenecks: [Misinformation and unproven therapies](https://onco.cc/bottlenecks/b-misinformation/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [Effects of St. John's wort on irinotecan metabolism](https://onco.cc/key-papers/paper-mathijssen-j-natl-cancer-inst/)

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