Drug & supplement interaction

Black Pepper + Cyclosporine

Cyclosporine brand names: Neoral, Gengraf, Sandimmune, Ciclosporine, Cequa, and others.

Moderate Interaction
The bottom line Moderate

Cyclosporine falls into 3 drug categories that Black Pepper can interact with; the most serious is rated moderate. Theoretically, black pepper might increase levels of P-glycoprotein substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Pepper and Cyclosporine

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Black Pepper interacts with whole categories of medication. Cyclosporine falls into 3 of those categories, so it can interact with Black Pepper in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

P-GLYCOPROTEIN SUBSTRATES

1 of 3

Why this applies to Cyclosporine

Cyclosporine falls under P-GLYCOPROTEIN SUBSTRATES — the group Black Pepper interacts with.

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thing with cyclosporine: it's pumped around your body by a transporter called P-glycoprotein, and it also has a narrow safety window, meaning small shifts in its blood level can matter quite a bit. The piperine in black pepper can block that pump in lab studies. If it does the same in people, more cyclosporine could stay in your system, pushing levels up and raising the odds of side effects like kidney strain, higher blood pressure, tremor, headache, or swollen gums.

Now, I don't want to alarm you. This is based only on test-tube research, not solid human studies, and a sprinkle of pepper on dinner is very different from a concentrated piperine supplement. Still, because cyclosporine is so dose-sensitive, please check with your transplant team or pharmacist before using any black pepper supplement.

References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  2. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  3. Aher, S., Biradar, S., Gopu, C. L., and Paradkar, A. Novel pepper extract for enhanced P-glycoprotein inhibition. J Pharm.Pharmacol. 2009;61(9):1179-1186. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

Cyclosporine also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: your body clears cyclosporine mainly through a liver and gut enzyme called CYP3A4. Piperine, the active part of black pepper, can slow that enzyme down in lab studies. If it slowed it down in real life, more cyclosporine could linger in your blood, which can mean higher levels and a greater chance of side effects like kidney strain, high blood pressure, tremor, headaches, or swollen gums.

Now the reassuring part: this is only seen in test-tube and computer-model research, not in actual people, so it's theoretical. The sprinkle of pepper on your dinner is very unlikely to matter. Concentrated piperine supplements (often paired with turmeric) are the bigger question mark. Since cyclosporine is a drug where small changes count, please check with your pharmacist or transplant team before adding one.

References
  1. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  2. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  3. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. PubMed
Moderate

CYCLOSPORINE (Neoral, Sandimmune)

3 of 3
Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist with cyclosporine: the piperine in black pepper can slow down some of the gut and liver enzymes (and transporters) that normally help clear this medication. If less is broken down, more cyclosporine can hang around in your blood. Since cyclosporine is a narrow therapeutic index drug, even small upward shifts can matter, possibly meaning more side effects like higher blood pressure, kidney strain, tremor, headache, or swollen gums.

I want to be honest about the evidence though: this is theoretical, seen in lab studies but not actually reported in real people. A little black pepper on your dinner is very unlikely to be a problem. Concentrated piperine supplements are where I'd pause. Please loop in your transplant team or pharmacist before adding one.

References
  1. Sharma, P., Varma, M. V., Chawla, H. P., and 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. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Black Pepper Also Interacts With Other Medications

Black Pepper has 975 moderate, 43 minor known drug interactions in our database — the Cyclosporine one above is among them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against Black Pepper

Covers the 2,830 medications we’ve checked against Black Pepper. Pick one to open its full report.

From our Q&A

Questions About Black Pepper or Cyclosporine

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Black Pepper or Cyclosporine, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Cyclosporine

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Cyclosporine page lists 229 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Asarabacca (major), Beer (major), Berberine (major) and Grapefruit (major).

By severity: 9 major · 182 moderate · 38 minor.

From our pharmacist’s overview on the Cyclosporine page

“Cyclosporine (Neoral, Sandimmune, Gengraf) keeps a transplanted organ from being rejected, and small shifts in its blood level can tip you toward rejection on one side or toxicity on the other. So approach these 229 interacting supplements with real care.”

Reviewed by 2 · Jul 18, 2026

Open the Cyclosporine interaction page

One more smart check

Taking Black Pepper as Part of a Dietary Supplement Product? Check It for Interactions

We hold 5,528 real supplement products containing Black Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Black Pepper. Your product may carry other ingredients that interact with Cyclosporine too, on top of Black Pepper — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Black Pepper and Cyclosporine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Black Pepper
Top 5%

#32 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Cyclosporine
Top 25%

#648 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Black Pepper

What is Black Pepper?

Black Pepper
  • Flavoring and culinary use
  • Digestive complaints like bloating and indigestion
  • Boosting absorption of other supplements
  • Antioxidant and anti-inflammatory support
  • Cold and congestion remedies

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (like curcumin from turmeric). Strong human evidence for black pepper treating specific health conditions is limited, so use supplement-strength products with care and check with your pharmacist.

Read the full Black Pepper monograph & all interactions
Medication

About Cyclosporine

What Is Cyclosporine Used For?

Brand names: Neoral, Gengraf, Sandimmune, Ciclosporine, Cequa, Verkazia, Vevye

Cyclosporine is prescribed to help prevent the body from rejecting a transplanted kidney, liver, or heart. It is often used alongside other immunosuppressive medicines as part of a full transplant care plan.

It is also used for adults with severe, active rheumatoid arthritis that hasn't responded well enough to methotrexate, and for adults with severe plaque psoriasis who haven't had success with other standard treatments.

See full Cyclosporine drug information
Keep checking

Other Drugs & Black Pepper

Browse every other medication we’ve checked against Black Pepper — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
975Moderate
43Minor
1,811No known interaction
Moderate

975 interactions

Showing 60 of 975 moderate interactions — see all 975 on the Black Pepper page.

Minor

43 interactions

No interaction 1,811 drugs checked — show the list
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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Pharmacist Counseling Corner

Taking Black Pepper and Cyclosporine Together: Common Questions

Can you take Black Pepper with Cyclosporine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 3 interactions listed for Black Pepper and Cyclosporine?
Cyclosporine belongs to more than one drug category, and Black Pepper interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Black Pepper and Cyclosporine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Cyclosporine and Black Pepper?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.