What this means in practice
Do not take St John's Wort while on irinotecan, and tell the oncology team about any supplement started between cycles. The confidence interval on the size of the effect is wide, but its direction is not in doubt and there is no safe amount to aim for.
What people say
A natural remedy for the low mood that comes with cancer treatment, and one that a person can add themselves without troubling the oncology team about it.
What the evidence supports
In five cancer patients given irinotecan with and without 18 days of St John's Wort in a randomised crossover, plasma levels of the active metabolite SN-38 fell by 42% (95% confidence interval 14% to 70%), and the bone-marrow suppression that normally accompanies an effective dose was substantially milder with the herb. The authors conclude patients on irinotecan should refrain from taking it (Mathijssen 2002). Reduced anticancer drug levels are listed among the well-documented interactions in the review literature (Borrelli 2009). Tumour response and survival were not measured.
How it is supposed to work
Irinotecan is a prodrug that the body converts into SN-38, the form that actually kills cancer cells. CYP3A4 diverts irinotecan down a competing inactive route, and hyperforin increases that enzyme, so less of the dose becomes SN-38.
Which way it runs
One-directional. St John's Wort reduces the amount of active drug the body makes from irinotecan. Irinotecan does not affect the herb. Because irinotecan is given as an infusion on a schedule while the herb is taken daily at home, the person receiving chemotherapy is often the only one who knows both are happening.
What is still missing
The reassuring sign and the harm are the same sign. Chemotherapy that suddenly feels easier to tolerate is what a 42% drop in active drug looks like from the inside, and there is no way to tell the two apart without measuring.
Sources
- Effects of St. John's wort on irinotecan metabolismMathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A, 2002
- Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observationsBorrelli F, Izzo AA, 2009