What this means in practice
Anyone on ciclosporin should not take St John's Wort. If someone has already started it, stopping abruptly is also a change in ciclosporin clearance, so it needs the transplant team and blood-level monitoring rather than a quiet decision at home.
What people say
A gentle herbal antidepressant. It is the kind of thing a transplant patient low in mood might reasonably reach for, and nothing about buying it suggests it belongs on a medication list.
What the evidence supports
Two heart transplant patients developed acute rejection attributed to this interaction (Ruschitzka 2000). Reduced blood ciclosporin concentrations are described as one of the best-documented St John's Wort interactions, supported by multiple case reports and clinical studies (Borrelli 2009). A systematic review of all St John's Wort safety evidence concludes that interactions with other drugs, ciclosporin in transplant patients above all, are the most relevant adverse effects of the herb (Knuppel 2004). The UK medicines regulator's own pharmacovigilance review lists ciclosporin among the medicines whose levels the herb reduces (Henderson 2002).
How it is supposed to work
Ciclosporin is cleared by CYP3A4 and moved by P-glycoprotein, and hyperforin in the extract increases both. Blood levels fall below the range that holds the immune response down, and the body starts rejecting the organ.
Which way it runs
One-directional. St John's Wort lowers ciclosporin levels; ciclosporin does not change what the herb does. The consequence falls entirely on the transplant patient, because ciclosporin is what keeps the immune system from attacking the transplanted organ.
What is still missing
The popular version is not wrong that the herb is gentle, and the safety reviews back that up for the herb taken on its own. What it misses is that the harm here is not a side effect of St John's Wort at all: it is the removal of a drug the patient needs, and the organ is what pays.
Sources
- Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observationsBorrelli F, Izzo AA, 2009
- St John's wort (Hypericum perforatum): drug interactions and clinical outcomesHenderson L, Yue QY, Bergquist C, Gerden B, Arlett P, 2002
- Adverse effects of St. John's Wort: a systematic reviewKnuppel L, Linde K, 2004