What happens when you take cyclosporine with st. john's wort?
Cyclosporine is a calcineurin inhibitor used to prevent rejection in organ transplant recipients and to treat severe autoimmune conditions such as psoriasis and rheumatoid arthritis. It has a narrow therapeutic window, meaning the gap between a level that protects the graft and one that fails to work is small. St. John's wort is an herbal product sold for low mood. When the two are combined, the herb speeds up the body's clearance of cyclosporine and its blood levels can fall to ineffective levels.
- St. John's wort contains a constituent called hyperforin, which activates the pregnane X receptor (PXR) in liver and intestinal cells.
- PXR activation increases production of the enzyme CYP3A4 and the transporter P-glycoprotein, the two systems that break down cyclosporine and pump it out of cells.
- Over the following one to two weeks, the body becomes far more efficient at clearing cyclosporine, so the same dose produces lower blood concentrations.
- As cyclosporine levels drop below the protective range, the immunosuppressive effect weakens and the transplanted organ is left underprotected.
- Because the effect comes from newly made enzymes, it does not switch off immediately when the herb is stopped; the raised clearance persists for one to two weeks while the extra enzymes are broken down.
Why is this important?
This is one of the best-documented herb-drug interactions on record, and the consequences can be serious. The concern is not a minor laboratory shift but the real possibility that an organ-protecting drug stops working.
In transplant recipients, subtherapeutic cyclosporine can allow acute rejection. Published case reports describe heart transplant patients who developed acute rejection within weeks of starting St. John's wort for low mood, with cyclosporine concentrations falling into the subtherapeutic range. Similar sequences have been reported in kidney transplant recipients, where cyclosporine needed to be increased substantially while the herb was taken and returned to baseline once it was stopped.
Acute rejection can require intensive treatment, may damage the graft, and in some cases threatens the transplanted organ. Beyond transplantation, anyone using cyclosporine for autoimmune disease may experience a flare if the medication becomes ineffective. The delayed recovery of enzyme activity after stopping the herb is part of why this needs medical oversight rather than a do-it-yourself fix.
What should you do?
The safe principle is simple: cyclosporine and St. John's wort should not be combined. How you act depends on where you are in the process, and any change should be made with your transplant team or prescriber rather than on your own.
Before starting either one: If you are about to start cyclosporine and have been taking St. John's wort, tell your transplant team or prescriber before your first dose. If you are on cyclosporine and considering any herbal or supplement product, check it for St. John's wort first and clear it with your pharmacist.
Every day while on cyclosporine: Take cyclosporine exactly as prescribed and keep your blood-level monitoring appointments. Avoid St. John's wort in every form, and read labels on multi-ingredient supplements for mood, sleep, stress, or menopause, where the herb is often blended in and not highlighted on the front.
After a change: If you realize you have been taking St. John's wort while on cyclosporine, do not simply stop and carry on. Contact your transplant coordinator or prescriber promptly. Because enzyme activity stays elevated for one to two weeks after stopping the herb, your team may want extra blood-level checks and may adjust your dose as clearance returns to normal. For mood symptoms, ask your physician about alternatives that are compatible with cyclosporine.
Which specific products are affected?
On the medication side, the interaction applies to all branded and generic systemic cyclosporine products, including Sandimmune, Neoral, Gengraf, and generic cyclosporine capsules and oral solutions. Topical and ophthalmic cyclosporine preparations, such as Restasis eye drops, have minimal systemic absorption and are far less of a concern, but they are still worth mentioning to your clinician.
On the herb side, the interaction occurs with any Hypericum perforatum (St. John's wort) extract regardless of brand or potency. This includes capsules, tablets, tinctures, and tea blends. It also includes multi-herb formulas marketed for depression, anxiety, sleep, or menopause, where St. John's wort is a common ingredient that may not appear prominently on the label. Given the severity of the consequences, no St. John's wort product should be considered safe alongside cyclosporine.
The science behind it
Human evidence for this interaction is consistent across both controlled studies and real-world cases.
A pharmacokinetic study in renal transplant patients (Bauer S, et al. Br J Clin Pharmacol. 2003; PMID 12580993) showed that adding St. John's wort meaningfully reduced cyclosporine exposure, including its peak and trough blood levels, confirming the enzyme-induction mechanism in transplant patients.
Two case reports document the clinical danger directly. Ruschitzka F, et al. (Lancet. 2000; PMID 10683008) described two heart transplant recipients who developed acute rejection after starting St. John's wort, with rejection linked to the fall in cyclosporine levels. Breidenbach T, et al. (Lancet. 2000; PMID 10866469) reported a renal transplant patient in whom St. John's wort lowered cyclosporine levels, with the requirement reversing once the herb was discontinued.
Frequently Asked Questions
Can I take St. John's wort if I'm on cyclosporine?
No. The combination can lower cyclosporine to ineffective levels and has caused organ rejection in transplant patients. It is treated as a contraindication.
What if I've already been taking both together?
Do not stop the herb on your own and assume the problem is solved. Contact your transplant team or prescriber promptly, because the herb's effect on cyclosporine clearance lingers for a week or two and your levels may need monitoring.
How quickly does the interaction happen?
Enzyme induction builds over roughly one to two weeks of taking St. John's wort, so cyclosporine levels tend to drift down over that period rather than instantly.
How long does the effect last after I stop the herb?
Because it works by making more clearance enzymes, the raised clearance can persist for about one to two weeks after stopping while those enzymes are broken down.
Are St. John's wort teas or combination supplements a problem too?
Yes. Teas, tinctures, and multi-herb blends for mood, sleep, or menopause can all contain St. John's wort, sometimes without prominent labeling. Check ingredients carefully and ask your pharmacist if unsure.
What can I use for low mood instead?
Ask your physician. Several prescription options can be chosen to work safely alongside cyclosporine, and your prescriber can select one with your other medications in mind.
Key takeaways
- Cyclosporine and St. John's wort should not be combined; the pairing is treated as a contraindication.
- St. John's wort speeds up cyclosporine clearance by inducing CYP3A4 and P-glycoprotein, lowering its blood levels.
- Subtherapeutic cyclosporine has caused acute organ rejection in published transplant case reports.
- St. John's wort hides in many mood, sleep, and menopause blends, so read supplement labels carefully.
- If you have been taking both, do not just stop on your own; contact your transplant team, as the effect lingers for one to two weeks and levels may need monitoring.