St John's wort: an interaction to avoid
St John's wort is a herbal antidepressant that switches on the liver enzymes that break down many cancer drugs, lowering the level of irinotecan, imatinib and many targeted tablets by up to half. It should not be taken during cancer treatment.
Overview
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.
How it works
Hyperforin activates PXR, increasing transcription of CYP3A4 and ABCB1, which accelerates clearance of drugs that are substrates of these systems.
- Interaction is well characterised and avoidable
- Prompts systematic supplement reconciliation
- Halves exposure to irinotecan and many oral anticancer drugs
- Effect lasts two weeks after stopping
- Serotonin syndrome with antidepressants
The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.
Irinotecan is a topoisomerase-blocking chemotherapy central to bowel and pancreatic cancer regimens (FOLFIRI, FOLFIRINOX, NALIRIFOX) and to salvage therapy in childhood sarcomas; it carries the same warhead as the deruxtecan ADC payloads.
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