The short answer
Not known in people. We found no human study of pippali, black pepper or piperine with cyclosporine. In rats, piperine nearly doubled how much of an oral cyclosporine dose was absorbed. In human gut cells grown in the lab, piperine blocked P-glycoprotein, a pump that pushes cyclosporine back out of the gut wall.
These studies used isolated piperine, a compound found in pippali (long pepper) and black pepper, not pippali powder. The lab authors note that piperine already raises blood levels of phenytoin and rifampicin in people. If you take cyclosporine, tell your transplant team before you start pippali, a churna that contains it, or a piperine or pepper supplement.
Ciclosporin is sold in India as Panimun Bioral.
At a glance
| What was seen | How it may work | Direction | Evidence |
|---|---|---|---|
| Piperine blocked cyclosporine transport in human gut cells (isolated piperine)[2] | P-glycoprotein inhibition; CYP3A4 also blocked in a separate test | Less cyclosporine pumped back out by gut cells, in the lab | In vitro |
| More of an oral cyclosporine dose absorbed in rats given piperine[1] | Proposed: P-glycoprotein inhibition | More cyclosporine in the blood, in rats | Animal |
No listing is not a clearance. A missing interaction here never means a combination is safe.
The evidence, study by study
Rat study, 2005 Animal
Rats given cyclosporine by mouth with piperine absorbed more of it: bioavailability rose from 18.4% to 33.1%, with wide variation between animals. Piperine did not do the same for cefotaxime, an antibiotic. The authors put the effect down to blocking P-glycoprotein. No transplant patients were studied.[1]
Laboratory study, 2002 In vitro
In a layer of human gut cells (Caco-2), piperine blocked the transport of cyclosporine and digoxin by P-glycoprotein. In human liver material it also blocked CYP3A4, tested with verapamil rather than cyclosporine. The concentrations used cannot be compared with eating pepper. Lab findings like this show a possible route for an interaction. They do not show that one happens in people.[2]
What your doctor may watch for
- Cyclosporine blood level and kidney function, especially serum creatinine, reviewed by your transplant or prescribing team.[3]
What to tell your prescribing doctor
You can read this out, or show them this page:
“I am taking, or planning to take, a product that contains pippali, black pepper extract or piperine (name of product, dose) along with cyclosporine. In rats, piperine increased cyclosporine absorption. Should my cyclosporine level and kidney function be checked?”
Withheld until review
Questions people ask
Is black pepper in food a problem?
We found no study of cyclosporine with pepper eaten in food. The studies used isolated piperine, and the lab concentrations cannot be compared with normal cooking.[2]
Which Ayurvedic medicines contain pippali?
Pippali is an ingredient of Sitopaladi Churna and Talisadi Churna in the Ayurvedic Formulary of India, among others. How much piperine a dose of these delivers is not known from these studies.[4][5]
Would taking them at different times help?
We found no study that tested a gap between piperine and cyclosporine, so no interval is known to help. Ask your transplant team.[1]
Related
Pippali, black pepper and phenytoin
Piperine, the compound in pippali and black pepper, raised phenytoin blood levels in two small Indian studies. Phenytoin has a narrow safe range.
InteractionPippali, black pepper and carbamazepine
Piperine from pepper raised carbamazepine levels in two small human studies. The studies used isolated piperine, not pippali powder.
InteractionNeem and transplant medicines (immunosuppressants)
In lab tests, neem blocked the liver enzymes that clear tacrolimus, which could raise its levels. We found no study of neem with transplant medicines.
FormulationSitopaladi Churna
A classical cough powder, about half sugar by weight. It contains pippali; piperine, a pepper compound, raised phenytoin levels in a small study.
Sources
- Sharma P, Varma MV, Chawla HP, Panchagnula R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco. 2005;60(11-12):874-883. PMID 16243320.
- Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther. 2002;302(2):645-650. PMID 12130727.
- Cyclosporine capsules, US prescribing information (DailyMed). Drug interactions and monitoring.
- Ayurvedic Formulary of India, Part I, 2nd revised English edition, 2003. Sitopaladi Curna, 7:34, printed page 116.
- Ayurvedic Formulary of India, Part I, 2nd revised English edition, 2003. Talisadya Curna, 7:13, printed pages 109-110.
Awaiting review by The Good Vaidya Medical Board. Prepared from the sources below and checked against each one.
Published 4 November 2026 · Last updated 4 November 2026
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