The short answer
Avoid starting St. John's wort while taking oral tacrolimus. It can lower tacrolimus exposure and undermine the protection your prescription provides. If you already take it, contact your transplant team before changing it because stopping can also change tacrolimus levels.
What this answer covers
This evidence concerns oral St. John's wort extracts and oral tacrolimus. Both immediate-release and prolonged-release tacrolimus have shown an interaction; individual herbal extracts can differ.
- Supplement or preparation
- St. John's wort (Hypericum perforatum)
- Medication ingredient
- tacrolimus
How strong is the direct evidence?
In ten kidney-transplant recipients, two weeks of St. John's wort lowered dose-corrected tacrolimus exposure substantially, and clinicians had to increase the tacrolimus dose. This measured loss of exposure supports the concern about inadequate immunosuppression, although the study was not designed to measure rejection rates.
Does the tacrolimus formulation matter?
A newer healthy-volunteer study found that exposure fell to 73% of baseline with immediate release and to 67% with prolonged release. That means reductions of 27% and 33%, not reductions of 73% and 67%. The study did not find a significant difference between formulations.
Why is taking them at different times inadequate?
St. John's wort can increase the activity of enzymes that process tacrolimus. This effect develops and persists beyond the time a dose is swallowed. The product information recommends avoiding the combination; no ordinary morning-versus-evening schedule has been shown to prevent it.
Why do I need help when stopping the herb?
Once the herb's effect fades, the same tacrolimus dose can produce more exposure. This is especially important if the dose was increased during herbal use. Tell your transplant team promptly, and let them plan repeat levels and any dose changes rather than changing the prescription yourself.
Evidence and practical considerations
Absorption & effectiveness
St. John's wort lowers oral tacrolimus exposure in transplant recipients and healthy volunteers.
- Exact scope
- Oral Hypericum perforatum extracts at studied regimens. with Tacrolimus, exact RxCUI 42316, inventory name tacrolimus, TTY IN. Oral systemic tacrolimus only. The US PROGRAF label describes tacrolimus capsules and anhydrous-equivalent strength; the UK capsule SmPC section 2 explicitly states tacrolimus as monohydrate. This bridges labeled monohydrate capsules to the IN, without merging different release formulations or transferring exposure results to topical or intravenous tacrolimus. No cyclosporine or other immunosuppressant evidence is substituted for tacrolimus evidence.
- Medication form and route
- oral
What remains uncertain
- Small trials; extract composition and enzyme phenotype can alter magnitude.
Read the supporting source summaries
Source 1: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Ten stable renal transplant recipients receiving tacrolimus and mycophenolate mofetil.
Dose-corrected tacrolimus exposure fell from 180 to 75.9 ng·h/mL. Median tacrolimus dose rose from 4.5 to 8 mg/day and remained 6.5 mg/day two weeks after stopping the herb.
How this applies: Direct exact-herb, exact-drug clinical evidence. Supports avoiding unsupervised use and monitoring after both starting and stopping.
Small study with active dose management, not a trial of rejection incidence. Product-specific induction may vary; abstract-only access.
Source 2: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Eighteen healthy volunteers.
Exposure fell TO 73% of baseline for immediate release and TO 67% for prolonged release, with no statistically significant formulation difference. Peak ratios were 61% and 69%.
How this applies: Direct evidence that prolonged release does not reliably avoid this induction interaction. Use original values rather than a later secondary misquotation.
Healthy volunteers, single drug doses, no transplant outcomes and abstract-only methods. Decreases are 27% and 33%, not 73% and 67%.
Research assessment: · Open full citations ↗
Timing & monitoring
Avoid unsupervised St. John's wort with tacrolimus; starting and stopping require clinician-directed monitoring rather than a spacing rule.
- Exact scope
- Oral Hypericum perforatum; both immediate and prolonged tacrolimus release forms. with Tacrolimus, exact RxCUI 42316, inventory name tacrolimus, TTY IN. Oral systemic tacrolimus only. The US PROGRAF label describes tacrolimus capsules and anhydrous-equivalent strength; the UK capsule SmPC section 2 explicitly states tacrolimus as monohydrate. This bridges labeled monohydrate capsules to the IN, without merging different release formulations or transferring exposure results to topical or intravenous tacrolimus. No cyclosporine or other immunosuppressant evidence is substituted for tacrolimus evidence.
- Medication form and route
- oral
What remains uncertain
- No universal dose adjustment; enzyme induction and its reversal persist beyond individual dose times.
Read the supporting source summaries
Source 1: regulatory product information
medicines.org.uk · Source check Sep 10, 2026
Population: Systemic oral tacrolimus users, principally transplant recipients.
Advises avoiding St. John's wort and high potassium intake. Names Schisandra sphenanthera extracts, not S. chinensis, among exposure-raising interactions. Monitor levels around interacting-product changes.
How this applies: Explicit monohydrate-to-IN identity bridge. Supports named-product precautions and monitoring without borrowing another drug's results.
Regulatory guidance, not an exact-product randomized outcome trial. Species-specific warning cannot establish a measured S. chinensis effect.
Source 2: original human clinical study
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Ten stable renal transplant recipients receiving tacrolimus and mycophenolate mofetil.
Dose-corrected tacrolimus exposure fell from 180 to 75.9 ng·h/mL. Median tacrolimus dose rose from 4.5 to 8 mg/day and remained 6.5 mg/day two weeks after stopping the herb.
How this applies: Direct exact-herb, exact-drug clinical evidence. Supports avoiding unsupervised use and monitoring after both starting and stopping.
Small study with active dose management, not a trial of rejection incidence. Product-specific induction may vary; abstract-only access.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Original evidence and current product information inspected; article distinguishes observed results, product limits and remaining uncertainty. | |
| Research summary published |
Article revision: 8a3279fac1be6e5b
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.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.