Drug & supplement interaction

Oregon Grape + Ethinyl Estradiol, Norgestimate

Ethinyl Estradiol, Norgestimate brand names: Ortho Tri-Cyclen 28, Ortho Tri-Cyclen Lo, Ortho-Cyclen, Mononessa, Previfem, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Norgestimate falls into 2 drug categories that Oregon Grape can interact with; the most serious is rated moderate. Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.

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

Oregon Grape and Ethinyl Estradiol, Norgestimate

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

Why Are There 2 Interactions?

Oregon Grape interacts with whole categories of medication. Ethinyl Estradiol, Norgestimate falls into 2 of those categories, so it can interact with Oregon Grape 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 Ethinyl Estradiol, Norgestimate

Ethinyl Estradiol, Norgestimate falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Oregon Grape interacts with.

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (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

Your birth control pill (Ortho Tri-Cyclen and similar) contains the hormones ethinyl estradiol and norgestimate, which your body partly clears through a liver enzyme called CYP3A4. Berberine, the active compound in Oregon grape, may gently slow that same enzyme down. In theory, that could let a little more of the estrogen hang around, which sometimes shows up as nausea, breast tenderness, bloating, or breakthrough spotting.

The good news: this is a theoretical concern based mostly on lab work, not strong real-world reports, and it leans toward slightly more hormone, not less, so it shouldn't make the pill stop working. Still, because berberine supplements are far more concentrated than anything in food, it's worth a quick chat with your pharmacist or doctor before pairing the two.

References
  1. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  2. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  3. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  4. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

2 of 2

Ethinyl Estradiol, Norgestimate also falls under P-GLYCOPROTEIN SUBSTRATES.

Theoretically, Oregon grape might increase serum levels of drugs that are P-glycoprotein (P-gp) substrates.
In vitro research suggests that Oregon grape extracts inhibit P-gp efflux.
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 for your birth control pill (Ethinyl Estradiol with Norgestimate). Oregon grape contains berberine, which in lab dishes seems to block a cellular pump called P-glycoprotein. Since the hormones in your pill are partly handled by that pump, the theory is that Oregon grape could let a little more hormone stay in your system. That might mean slightly stronger estrogen-type effects, like nausea, breast tenderness, headaches, or bloating.

The honest truth is that this is based only on test-tube data, not on real people, so we don't know if it actually matters in everyday life. Food-amount exposure is unlikely to be an issue, but concentrated supplements are a bigger unknown. Before pairing them, just run it by your pharmacist or doctor so they can weigh in.

References
  1. Fan Y, Zhou Z, Zhang L. Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines. J Pharm Pharm Sci 2024;26:11927. 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

Oregon Grape Also Interacts With Other Medications

Oregon Grape has 1,217 moderate known drug interactions in our database — the Ethinyl Estradiol, Norgestimate 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 Oregon Grape

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

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Norgestimate

This page covers Oregon Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Norgestimate page lists 239 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 6 major · 195 moderate · 38 minor.

Open the Ethinyl Estradiol, Norgestimate interaction page

One more smart check

Taking Oregon Grape as Part of a Dietary Supplement Product? Check It for Interactions

We hold 740 real supplement products containing Oregon Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Oregon Grape. Your product may carry other ingredients that interact with Ethinyl Estradiol, Norgestimate too, on top of Oregon Grape — 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 Oregon Grape and Ethinyl Estradiol, Norgestimate 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 Oregon Grape
Top 25%

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

29 days ago today
Medication Ethinyl Estradiol, Norgestimate
Steady interest

#1,552 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 Oregon Grape

What is Oregon Grape?

Oregon Grape
  • Psoriasis (topical)
  • Eczema and other skin conditions
  • Digestive upset
  • Mild skin infections
  • General 'detox' or tonic use

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for other uses is limited. Talk with your pharmacist or doctor before using it, and avoid it during pregnancy and breastfeeding.

Read the full Oregon Grape monograph & all interactions
Keep checking

Other Drugs & Oregon Grape

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

0Major
1,217Moderate
0Minor
1,612No known interaction
Moderate

1,217 interactions

Showing 60 of 1,217 moderate interactions — see all 1,217 on the Oregon Grape page.

No interaction 1,612 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 Oregon Grape and Ethinyl Estradiol, Norgestimate Together: Common Questions

Can you take Oregon Grape with Ethinyl Estradiol, Norgestimate?
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 Oregon Grape and Ethinyl Estradiol, Norgestimate?
Ethinyl Estradiol, Norgestimate belongs to more than one drug category, and Oregon Grape 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 Oregon Grape and Ethinyl Estradiol, Norgestimate 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.