St John's wort and Ciclosporin / tacrolimus

Yes — there is a documented interaction between these two, and it has a named mechanism. CYP3A4 induction.

Critical St John's wort induces CYP3A4; Ciclosporin / tacrolimus is cleared by it

Mechanism: CYP3A4 induction

St John's wort increases the enzyme that clears Ciclosporin / tacrolimus, so Ciclosporin / tacrolimus is destroyed faster and its blood level falls. This is the mirror hazard, and the harder one to notice: nothing feels wrong, the medicine simply stops working. The mirror hazard: the drug is destroyed faster and silently stops working. Transplant rejection, HIV breakthrough, contraceptive failure.

Moore et al. identified PXR activation as the mechanism. Ruschitzka et al. reported acute heart transplant rejection from ciclosporin level collapse; Piscitelli et al. measured a 57% median fall in indinavir AUC in healthy volunteers.

The transplant-rejection case: induction drops the level below the therapeutic window and the graft is attacked.

What to watch for. Loss of effect rather than toxicity — and, when the inducer is STOPPED, the level climbing back up over days to weeks with no change in prescription.

Sources: Moore LB 2000, Ruschitzka F 2000, Piscitelli SC 2000, Henderson L 2002

The mechanism, generalised

Read the mechanism page and you can apply this to substances that are not on it: CYP3A4 induction.

Substance pages: St John's wort · Ciclosporin / tacrolimus.

What a clean result means here

A clean result means NO DOCUMENTED INTERACTION IN THIS DATASET. It does not mean safe, and it is not a clearance. Most substances are not in this dataset at all, and for many pairs that are, nobody has ever studied the combination.

In this dataset

  • Monoamine oxidase inhibition (prescription MAOIs, RIMAs, linezolid, methylene blue, harmala alkaloids)
  • Serotonergic drugs and the serotonin-toxicity mechanism
  • Dietary tyramine and L-dopa loads
  • The major cytochrome P450 pathways: CYP3A4, CYP2D6, CYP1A2, CYP2C9, CYP2C19 — inhibition and induction
  • P-glycoprotein inhibition and induction
  • 11β-HSD2 inhibition (the licorice mechanism) and the potassium consequences that follow it
  • QT prolongation as an additive pharmacodynamic axis
  • Culinary seasonings and common foods with documented pharmacological activity
  • A selected set of narrow-therapeutic-index drugs where those shifts matter most

Not in this dataset

  • Any substance not named in this dataset — which is most substances. There are tens of thousands of marketed drugs and this table holds fewer than a hundred entries.
  • Phase-2 conjugation (UGT, SULT, NAT2, COMT) except where a specific entry names it. The oilahuasca corpus turns heavily on phase 2 and this engine models it only in passing.
  • Pharmacogenomics. CYP2D6 and CYP2C19 are strongly polymorphic; a poor metaboliser and an ultra-rapid metaboliser can have opposite outcomes from the same pair, and this engine does not know your genotype.
  • Dose, timing, duration, formulation and route — all of which change whether a documented interaction is clinically real for you.
  • Renal and hepatic impairment, age, pregnancy, and body composition.
  • Additive sedation, respiratory depression, bleeding risk, hypoglycaemia and most other pharmacodynamic axes beyond the ones listed above.
  • Herb–herb interactions outside the named entries, and essentially the whole botanical world: most plants have no interaction literature at all.
  • Allergy, intolerance, and contamination or adulteration of unregulated products.
  • Anything published after the last-reviewed date below.

72 substances, 20 mechanisms, 64 citations. Last reviewed . Primary literature (every DOI resolved against the Crossref API) and FDA drug labelling. There is no free, openly-licensed, comprehensive drug-interaction dataset to draw on; NLM retired its Drug Interaction API on 2024-01-02 and DrugBank's interaction set is a commercial licence.

References

  1. Moore LB, Goodwin B, Jones SA, et al. (2000). St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. PNAS. doi:10.1073/pnas.130155097
  2. Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G (2000). Acute heart transplant rejection due to Saint John's wort. The Lancet. doi:10.1016/S0140-6736(99)05467-7
  3. Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J (2000). Indinavir concentrations and St John's wort. The Lancet. doi:10.1016/S0140-6736(99)05712-8
  4. Henderson L, Yue QY, Bergquist C, Gerden B, Arlett P (2002). St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology. doi:10.1046/j.1365-2125.2002.01683.x

Every DOI above was resolved against the Crossref API on 2026-09-09 and the returned title checked against the one printed here. Three DOIs in the first draft resolved to real but different papers and were corrected before publication.

Last reviewed . All interaction pages.