Drug & supplement interaction

Black Pepper + Norelgestromin, Ethinyl Estradiol

Norelgestromin, Ethinyl Estradiol brand names: Ortho Evra, Evra.

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

Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol

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. Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol

Norelgestromin, Ethinyl Estradiol 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

If you wear the Ortho Evra patch (norelgestromin plus ethinyl estradiol), here's the quick version on black pepper. Piperine, the active compound in pepper, can slow down a transport pump called P-glycoprotein. In theory, that might let a little more of these hormones stay in your body, which could nudge up side effects like nausea, breast tenderness, headaches, or spotting.

The honest truth is this is very weak evidence. It comes only from lab dish studies, not real people, and the patch delivers hormones through your skin rather than your gut where pepper acts most. Pepper sprinkled on your food is not a concern at all. If you take a concentrated piperine supplement and notice changes, just check in with your pharmacist or doctor.

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 3

Norelgestromin, Ethinyl Estradiol 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

Your Ortho Evra patch releases two hormones, ethinyl estradiol and norelgestromin, that your liver clears using an enzyme called CYP3A4. Piperine, the active part of black pepper, may slow that enzyme down a bit in lab tests. In theory, that could let slightly more estrogen linger in your body, which can mean more of the usual hormonal complaints like nausea, breast tenderness, headaches, or spotting.

Here's the reassuring part: this is based only on test-tube and computer modeling work, and it has not been seen in real people. Everyday pepper on your food is no concern. If you take a concentrated piperine or turmeric-with-pepper supplement, just mention it to your pharmacist so they can keep an eye on things.

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
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 3

Norelgestromin, Ethinyl Estradiol also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.
Severity Minor 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

If you wear the Ortho Evra patch (which delivers an estrogen and a progestin), you may wonder if black pepper messes with it. Here's the honest picture: lab studies hint that piperine, the active part of black pepper, might gently speed up a liver enzyme called CYP1A2 that helps process estrogen. In theory, that could lower hormone levels a little and, at the far end, weaken pregnancy protection. But this is only test-tube data, and nothing like it has been seen in real people.

So I wouldn't lose sleep over the pepper on your dinner. Concentrated piperine supplements are the bigger question mark, not normal cooking. If you take one regularly, just mention it to your pharmacist or doctor so they can weigh in.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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 Norelgestromin, Ethinyl Estradiol 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. Norelgestromin, Ethinyl Estradiol)
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 Norelgestromin, Ethinyl Estradiol

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 Norelgestromin, Ethinyl Estradiol, 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 Norelgestromin, Ethinyl Estradiol

This page covers Black Pepper only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Norelgestromin, Ethinyl Estradiol page lists 203 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 2 major · 168 moderate · 33 minor.

From our pharmacist’s overview on the Norelgestromin, Ethinyl Estradiol page

“St. John's wort is the first entry to check if you wear the Ortho Evra patch (norelgestromin and ethinyl estradiol).”

Reviewed by 2 · Jul 18, 2026

Open the Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol
Steady interest

#1,915 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
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 Norelgestromin, Ethinyl Estradiol, 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 Norelgestromin, Ethinyl Estradiol supplement interactions › Every supplement checked against Norelgestromin, Ethinyl Estradiol, ranked by severity 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 Norelgestromin, Ethinyl Estradiol Together: Common Questions

Can you take Black Pepper with Norelgestromin, Ethinyl Estradiol?
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 Norelgestromin, Ethinyl Estradiol?
Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol 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 Norelgestromin, Ethinyl Estradiol 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.