The short answer
St. John's wort can substantially lower cyclosporine levels and has been linked to transplant rejection and graft loss. Guidance supports avoiding the combination; spacing doses does not prevent the interaction, and its effects can persist after St. John's wort is stopped.
What this answer covers
Applies to systemic cyclosporine, with much of the direct evidence from oral treatment in transplant recipients; it does not apply to cyclosporine eye drops.
- Supplement or preparation
- St. John's wort
- Medication ingredient
- cyclosporine
Evidence and practical considerations
Absorption & effectiveness
Multiple exact-cyclosporine human case reports and renal-transplant pharmacokinetic studies show substantial concentration reductions after St. John's wort, with subtherapeutic exposure, rejection, and graft loss. Official labeling and NCCIH warn against co-use. Adjudication lead: supported, clinically major, systemic exposure interaction. Animal, in-vitro, product, route, and formulation boundaries were applied without silent extrapolation.
- Exact scope
- St. John's wort with cyclosporine
- Medication form and route
- systemic cyclosporine; ophthalmic use excluded
- Timing or duration
- Human evidence shows onset by day 3, large change by 14 days, and rejection after 4–8 weeks; reversal may exceed 2 weeks.
What remains uncertain
- Exact cyclosporine RxCUI 3008 IN is preserved; precise ingredients, salts, combinations, and other calcineurin inhibitors are not silently merged.
- Modified and nonmodified systemic finished products remain distinct unless the source explicitly bridges active moiety and formulation.
- Systemic evidence is not transferred to ophthalmic cyclosporine.
- Preclinical plausibility is not treated as a human clinical interaction; no conflicting_evidence decision is used without genuinely opposing exact endpoints.
Factors that may matter: St. John's wort hyperforin content and dose; oral cyclosporine formulation and baseline trough; transplant rejection vulnerability; other CYP3A4 or P-glycoprotein inducers.
Read the supporting source summaries
Source 1: peer-reviewed biomedical evidence
pubmed.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: A 29-year-old kidney-pancreas transplant recipient with stable graft function and stable cyclosporine concentrations before self-starting St. John's wort.
Cyclosporine became subtherapeutic during St. John's wort use and rejection followed; levels recovered after withdrawal, but chronic rejection developed.
Single case report; botanical product and dose were not standardized, and concomitant clinical factors cannot be fully excluded.
Source 2: peer-reviewed biomedical evidence
pmc.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: Eleven renal-transplant recipients stabilized on oral cyclosporine.
Cmax, trough, and AUC fell about 42%, 41%, and 46%; median cyclosporine dose rose from 2.7 to 4.2 mg/kg/day.
Small uncontrolled transplant cohort; results depend on the tested botanical extract and systemic cyclosporine regimen.
Source 3: official prescribing information
dailymed.nlm.nih.gov · Source check Jul 25, 2026
Population: Patients receiving labeled oral nonmodified cyclosporine capsules.
The label reports marked concentration reduction with St. John's wort, subtherapeutic levels, organ rejection, and graft loss.
Regulatory labeling summarizes reports rather than a controlled trial and is specific to systemic oral use.
Research assessment: · Open full citations ↗
Side effects & toxicity
Exact human case reports and official labeling connect St. John's wort-induced cyclosporine underexposure to organ rejection and graft loss. Adjudication lead: supported major safety risk for systemic cyclosporine. Animal, in-vitro, product, route, and formulation boundaries were applied without silent extrapolation.
- Exact scope
- St. John's wort with cyclosporine
- Medication form and route
- systemic cyclosporine; ophthalmic use excluded
- Timing or duration
- Underexposure may begin by day 3, is large by 2 weeks, and has caused rejection after 4–8 weeks; induction may persist beyond 2 weeks after stopping.
What remains uncertain
- Exact cyclosporine RxCUI 3008 IN is preserved; precise ingredients, salts, combinations, and other calcineurin inhibitors are not silently merged.
- Modified and nonmodified systemic finished products remain distinct unless the source explicitly bridges active moiety and formulation.
- Systemic evidence is not transferred to ophthalmic cyclosporine.
- Preclinical plausibility is not treated as a human clinical interaction; no conflicting_evidence decision is used without genuinely opposing exact endpoints.
Factors that may matter: transplant rejection vulnerability; botanical hyperforin content and adherence; baseline cyclosporine trough and formulation; delay in monitoring after starting or stopping.
Read the supporting source summaries
Source 1: peer-reviewed biomedical evidence
pubmed.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: A 29-year-old kidney-pancreas transplant recipient with stable graft function and stable cyclosporine concentrations before self-starting St. John's wort.
Cyclosporine became subtherapeutic during St. John's wort use and rejection followed; levels recovered after withdrawal, but chronic rejection developed.
Single case report; botanical product and dose were not standardized, and concomitant clinical factors cannot be fully excluded.
Source 2: peer-reviewed biomedical evidence
pubmed.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: Organ-transplant recipients represented in clinical reports and cyclosporine interaction data summarized by the article.
The article concludes that St. John's wort lowered cyclosporine levels and led to rejection in several cases.
Synthesis of reports rather than one controlled trial; botanical dose and transplant regimens varied.
Source 3: official prescribing information
dailymed.awsprod.nlm.nih.gov · Source check Jul 25, 2026
Population: Patients receiving labeled oral nonmodified cyclosporine capsules for systemic immunosuppression.
Prescribing information reports marked concentration reduction, subtherapeutic levels, rejection, and graft loss.
Label evidence gives no incidence, standardized botanical dose, or comparative estimate.
Research assessment: · Open full citations ↗
Timing & monitoring
Official labeling, NCCIH guidance, human PK studies, and rejection cases support avoiding St. John's wort during systemic cyclosporine treatment. Timing separation cannot reliably prevent enzyme induction. Adjudication lead: supported avoidance. Animal, in-vitro, product, route, and formulation boundaries were applied without silent extrapolation.
- Exact scope
- St. John's wort with cyclosporine
- Medication form and route
- systemic cyclosporine; ophthalmic use excluded
- Timing or duration
- Avoid throughout systemic therapy and the post-withdrawal induction period; dose separation does not prevent induction.
What remains uncertain
- Exact cyclosporine RxCUI 3008 IN is preserved; precise ingredients, salts, combinations, and other calcineurin inhibitors are not silently merged.
- Modified and nonmodified systemic finished products remain distinct unless the source explicitly bridges active moiety and formulation.
- Systemic evidence is not transferred to ophthalmic cyclosporine.
- Preclinical plausibility is not treated as a human clinical interaction; no conflicting_evidence decision is used without genuinely opposing exact endpoints.
Factors that may matter: unreported self-medication; extract potency; transplant indication; timing of trough monitoring.
Read the supporting source summaries
Source 1: peer-reviewed biomedical evidence
pubmed.ncbi.nlm.nih.gov · Source check Jul 25, 2026
Population: A 29-year-old kidney-pancreas transplant recipient with stable graft function and stable cyclosporine concentrations before self-starting St. John's wort.
Cyclosporine became subtherapeutic during St. John's wort use and rejection followed; levels recovered after withdrawal, but chronic rejection developed.
Single case report; botanical product and dose were not standardized, and concomitant clinical factors cannot be fully excluded.
Source 2: NIH patient drug guidance
medlineplus.gov · Source check Jul 25, 2026
Population: Patients taking oral cyclosporine or cyclosporine modified for transplant prevention, rheumatoid arthritis, or psoriasis.
Guidance says to avoid grapefruit, discuss potassium-rich foods and salt substitutes, disclose St. John's wort, and report low cholesterol, low magnesium, or high potassium.
Patient guidance supplies management instructions without comparative estimates, assay details, or evidence grading.
Source 3: official prescribing information
dailymed.nlm.nih.gov · Source check Jul 25, 2026
Population: Patients receiving labeled oral cyclosporine capsules modified in transplant, rheumatoid-arthritis, or psoriasis care.
Label says grapefruit raises levels and should be avoided, St. John's wort can cause severe underexposure, and potassium and magnesium require monitoring.
Formulation-specific regulatory guidance without a unified trial or absolute event rates.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Research summary published |
Article revision: bc3fcaa619050647
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
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