Drug & supplement interaction

Black Pepper + Hydrocortisone

Hydrocortisone brand names: Cortef, Hydrocortone, Carmol HC cream, Hydrocortisone Iodoquinol Cream, Vytone Cream, and others.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Hydrocortisone falls into 2 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
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Black Pepper and Hydrocortisone

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Black Pepper interacts with whole categories of medication. Hydrocortisone falls into 2 of those categories, so it can interact with Black Pepper in 2 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 2

Why this applies to Hydrocortisone

Hydrocortisone 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 gist: black pepper's active compound, piperine, may block a cellular pump called P-glycoprotein that helps usher certain drugs out of your body. Hydrocortisone is one of the substances that pump can move. If the pump is slowed, a little more hydrocortisone could stay in your system, which in theory might nudge up its effects and side effects (think fluid retention, higher blood sugar, mood or sleep changes, or stomach upset with longer use).

That said, this is based only on lab studies, not real people, so I wouldn't lose sleep over it. The sprinkle of pepper on your dinner is no concern. Concentrated piperine supplements are where I'd be a bit more cautious. If you take hydrocortisone regularly, just run your supplement plan by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
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 2

Hydrocortisone 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 uses an enzyme called CYP3A4 to break down hydrocortisone. In lab and computer studies, piperine (the active part of black pepper) appears to slow that enzyme down. If that happened in real life, more hydrocortisone could linger in your system, which might mean stronger steroid effects, such as fluid retention, higher blood sugar, mood changes, or trouble sleeping.

But I want to keep this in perspective. This has only been seen in test tubes and simulations, never confirmed in people, so the evidence is weak. Normal cooking amounts of black pepper are very unlikely to matter. Concentrated piperine supplements are where I'd be more cautious. If you take one regularly, just run it by your pharmacist or doctor before changing anything.

Contact Dr. Brian directly if you have additional questions on this interaction
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

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 Hydrocortisone one above is among them. If you take anything else, check it against the full list below.

Moderate 975 Minor 43 No known interaction 1,812 (incl. Hydrocortisone)
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 Hydrocortisone

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 Hydrocortisone, 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 Hydrocortisone

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Hydrocortisone page lists 205 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Grapefruit (major), Lily-of-the-valley (major), St. John's Wort (major) and Acacia Rigidula (moderate).

By severity: 4 major · 164 moderate · 37 minor.

Open the Hydrocortisone 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 Hydrocortisone 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 Hydrocortisone 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%

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

29 days ago today
Medication Hydrocortisone
Top half

#950 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 Hydrocortisone

What Is Hydrocortisone Used For?

Brand names: Cortef, Hydrocortone, Carmol HC cream, Hydrocortisone Iodoquinol Cream, Vytone Cream, Massengil Medicated Towelettes, Dioderm, Efcortelan Cream, Mildison, Alphaderm, Calmurid HC, Efcortelan Ointment, Texacort, Alkindi Sprinkle

Hydrocortisone comes in many products, and each one is approved for different uses. Which one you get depends on the condition being treated.

Cortef tablets are used for adrenal insufficiency, congenital adrenal hyperplasia, rheumatic disorders (such as rheumatoid arthritis and gouty arthritis) and collagen diseases such as lupus. Hydrocortisone sodium succinate and Solu-Cortef injections are used when oral therapy is not feasible, for severe allergic states, skin diseases, and adrenal insufficiency. Alkindi (oral granules) is used as replacement therapy in children with adrenocortical insufficiency. Cortenema, Hydrocortisone Rectal Suspension and Cortifoam are used for ulcerative colitis or ulcerative proctitis. Topical hydrocortisone butyrate and valerate products, including Evesse lotion, are used for itchy, inflamed skin conditions and atopic dermatitis.

See full Hydrocortisone 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
975 Moderate 43 Minor 1,811 No 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

We also checked Black Pepper against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,811 medications checked with no known interaction — see the full Black Pepper list.

See the full Black Pepper interactions page
See every supplement checked against Hydrocortisone, ranked by severity
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

Keep exploring
Black Pepper monograph › Uses, safety, and every drug interaction in one place Hydrocortisone supplement interactions › Every supplement checked against Hydrocortisone, ranked by severity Hydrocortisone drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Black Pepper and Hydrocortisone Together: Common Questions

Can you take Black Pepper with Hydrocortisone?
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 2 interactions listed for Black Pepper and Hydrocortisone?
Hydrocortisone 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 Hydrocortisone 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 Hydrocortisone 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.