Drug & supplement interaction

Indian Long Pepper + Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol brand name: Annovera.

Moderate Interaction
The bottom line Moderate

Segesterone Acetate, Ethinyl Estradiol falls into 2 drug categories that Indian Long Pepper can interact with; the most serious is rated moderate. Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Indian Long Pepper and Segesterone Acetate, Ethinyl Estradiol

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

Why Are There 2 Interactions?

Indian Long Pepper interacts with whole categories of medication. Segesterone Acetate, Ethinyl Estradiol falls into 2 of those categories, so it can interact with Indian Long Pepper in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

1 of 2

Why this applies to Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Indian Long Pepper interacts with.

Theoretically, Indian long pepper might increase the effects and adverse effects of CYP3A4 substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, inhibits CYP3A4.
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

Annovera is your vaginal ring that releases two hormones, segesterone acetate and ethinyl estradiol. Both are cleared by a liver enzyme called CYP3A4. In lab studies, piperine (the active compound in Indian long pepper) appears to slow that enzyme down. In theory, that could let a little more estrogen and progestin linger in your blood, which might bump up typical hormone side effects like nausea, breast tenderness, headaches, bloating, or mood changes.

I want to be honest though: this is only a theoretical concern from test-tube work, not real patient cases, and an occasional sprinkle in food is unlikely to matter. If you use long pepper supplements regularly, just give your pharmacist or doctor a heads-up so they can keep an eye on things.

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
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Segesterone Acetate, Ethinyl Estradiol also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Indian long pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of Indian long pepper, can 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

Annovera is a vaginal ring that slowly releases two hormones, segesterone acetate and ethinyl estradiol, to prevent pregnancy. The thinking here is that piperine, the main compound in Indian long pepper, can block a transporter called P-glycoprotein in lab studies. If that happened in the body, it could nudge hormone levels a bit higher, which might mean more of the usual estrogen-related effects like nausea, breast tenderness, headaches, or bloating.

The good news: this is only a theory based on test-tube work, not real people, so I wouldn't lose sleep over it. A sprinkle of pepper in your food almost certainly won't matter. If you take concentrated long pepper supplements regularly, just mention it to your pharmacist or doctor so they can keep an eye on things.

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

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

Indian Long Pepper Also Interacts With Other Medications

Indian Long Pepper has 893 moderate, 3 minor known drug interactions in our database — the Segesterone Acetate, Ethinyl Estradiol 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 Indian Long Pepper

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

Everything else you take

See Every Supplement That Interacts With Segesterone Acetate, Ethinyl Estradiol

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

The most serious there right now: Beer (major), Grapefruit (major), Siberian Cocklebur (major), St. John's Wort (major) and Wine (major).

By severity: 5 major · 193 moderate · 31 minor.

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

“St. John's wort is the interaction I would explain first to anyone using Annovera (segesterone acetate with ethinyl estradiol, a vaginal ring for birth control).”

Reviewed by 2 · Jul 18, 2026

Open the Segesterone Acetate, Ethinyl Estradiol interaction page

One more smart check

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

We hold 597 real supplement products containing Indian Long Pepper, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Indian Long Pepper. Your product may carry other ingredients that interact with Segesterone Acetate, Ethinyl Estradiol too, on top of Indian Long 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 Indian Long Pepper and Segesterone Acetate, 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 Indian Long Pepper
Top 25%

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

29 days ago today
Medication Segesterone Acetate, Ethinyl Estradiol
Top 25%

#418 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 Indian Long Pepper

What is Indian Long Pepper?

Indian Long Pepper
  • Digestive upset
  • Respiratory and cough complaints
  • Boosting absorption of other supplements
  • Pain and inflammation
  • General wellness in Ayurveda

Indian long pepper (pippali) is a spice long used in Ayurvedic medicine and is best known for its piperine content, which may increase how well the body absorbs certain other substances. Modern human research on its health benefits is limited, so use it cautiously and let your pharmacist or doctor know if you take it regularly.

Read the full Indian Long Pepper monograph & all interactions
Keep checking

Other Drugs & Indian Long Pepper

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

0Major
893Moderate
3Minor
1,933No known interaction
Moderate

893 interactions

Showing 60 of 893 moderate interactions — see all 893 on the Indian Long Pepper page.

Minor

3 interactions

No interaction 1,933 drugs checked — show the list

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

Showing the 60 most looked-up of 1,933 medications checked with no known interaction — see the full Indian Long Pepper 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 Indian Long Pepper and Segesterone Acetate, Ethinyl Estradiol Together: Common Questions

Can you take Indian Long Pepper with Segesterone Acetate, 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 2 interactions listed for Indian Long Pepper and Segesterone Acetate, Ethinyl Estradiol?
Segesterone Acetate, Ethinyl Estradiol belongs to more than one drug category, and Indian Long 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 Indian Long Pepper and Segesterone Acetate, 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

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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.