Drug & supplement interaction

Grape + Relugolix, Estradiol, Norethindrone Acetate

Relugolix, Estradiol, Norethindrone Acetate brand name: Myfembree.

Moderate Interaction
The bottom line Moderate

Relugolix, Estradiol, Norethindrone Acetate falls into 2 drug categories that Grape can interact with; the most serious is rated moderate. Theoretically, grape juice might reduce the levels of CYP1A2 substrates.

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

Grape and Relugolix, Estradiol, Norethindrone Acetate

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

Why Are There 2 Interactions?

Grape interacts with whole categories of medication. Relugolix, Estradiol, Norethindrone Acetate falls into 2 of those categories, so it can interact with 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 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Relugolix, Estradiol, Norethindrone Acetate

Relugolix, Estradiol, Norethindrone Acetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Grape interacts with.

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.
Severity Moderate Likelihood Possible Evidence B

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 Myfembree (relugolix, estradiol, norethindrone) and grape products. Grape juice may gently speed up a liver enzyme called CYP1A2, which helps break down certain medicines. If grape nudges that enzyme to work faster, in theory it could lower the levels of components in Myfembree and make them a little less effective. For a hormone therapy used to manage heavy bleeding or pain from fibroids or endometriosis, that could mean less symptom control.

That said, this is mostly theoretical, based on a small study using a different drug. Everyday amounts of grapes you eat are very unlikely to matter. If you're considering a concentrated grape seed extract supplement, just run it by your pharmacist or doctor first.

References
  1. Xiao Dong S, Zhi Ping Z, Zhong Xiao W, et al. Possible enhancement of the first-pass metabolism of phenacetin by ingestion of grape juice in Chinese subjects. Br J Clin Pharmacol 1999;48:638-40. PubMed
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

Relugolix, Estradiol, Norethindrone Acetate also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have 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

Myfembree combines three active hormones (relugolix, estradiol, and norethindrone) that your liver processes in part through an enzyme called CYP3A4. None of these are prodrugs, so they already work in the form you take them. Grape seed extract might nudge this enzyme one way or the other, but honestly the science is muddy. Lab tests hint it could slow the enzyme (which could raise hormone levels and side effects like nausea, headache, breast tenderness, mood changes, or spotting), while animal studies hint it could speed it up (which might weaken the medicine's control of your symptoms).

Here's the reassuring part: this has never actually been reported in people, and eating grapes is not a concern. If you're thinking about a concentrated grape seed extract supplement, just run it by your pharmacist or doctor first.

References
  1. Nishikawa, M., Ariyoshi, N., Kotani, A., Ishii, I., Nakamura, H., Nakasa, H., Ida, M., Nakamura, H., Kimura, N., Kimura, M., Hasegawa, A., Kusu, F., Ohmori, S., Nakazawa, K., and Kitada, M. Effects of continuous ingestion of green tea or grape seed extra
  2. Etheridge, A. S., Black, S. R., Patel, P. R., So, J., and Mathews, J. M. An in vitro evaluation of cytochrome P450 inhibition and P-glycoprotein interaction with goldenseal, Ginkgo biloba, grape seed, milk thistle, and ginseng extracts and their constitu

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

Grape Also Interacts With Other Medications

Grape has 867 moderate, 42 minor known drug interactions in our database — the Relugolix, Estradiol, Norethindrone Acetate 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 Grape

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

From our Q&A

Questions About Grape or Relugolix, Estradiol, Norethindrone Acetate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grape or Relugolix, Estradiol, Norethindrone Acetate, 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 Relugolix, Estradiol, Norethindrone Acetate

This page covers Grape only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Relugolix, Estradiol, Norethindrone Acetate page lists 219 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), American Hellebore (major), Arsenic (major), Cesium (major) and Ephedra (major).

By severity: 8 major · 174 moderate · 37 minor.

From our pharmacist’s overview on the Relugolix, Estradiol, Norethindrone Acetate page

“Grapefruit is where I would start on this page. Myfembree (relugolix, estradiol, and norethindrone acetate) depends on the CYP3A4 enzyme to be cleared, and grapefruit juice blocks that enzyme, raising drug levels and side effect risk.”

Reviewed by 2 · Jul 18, 2026

Open the Relugolix, Estradiol, Norethindrone Acetate interaction page

One more smart check

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

We hold 8,053 real supplement products containing Grape, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grape. Your product may carry other ingredients that interact with Relugolix, Estradiol, Norethindrone Acetate too, on top of 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 Grape and Relugolix, Estradiol, Norethindrone Acetate 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 Grape
Top 5%

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

29 days ago today
Medication Relugolix, Estradiol, Norethindrone Acetate
Steady interest

#2,435 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 Grape

What is Grape?

Grape
  • Antioxidant support
  • Heart and circulation health
  • Vein problems (such as varicose veins)
  • Eye health
  • General anti-inflammatory support

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is healthy and generally safe, the supplement evidence for treating specific conditions is mostly limited or preliminary. Talk with your pharmacist or doctor before starting a grape supplement.

Read the full Grape monograph & all interactions
Medication

About Relugolix, Estradiol, and Norethindrone

What Is Relugolix, Estradiol, and Norethindrone Used For?

Brand name: Myfembree

Myfembree is approved for two conditions in premenopausal women: managing heavy menstrual bleeding caused by uterine fibroids (non-cancerous growths in the uterus), and managing moderate to severe pain caused by endometriosis (a condition where tissue similar to the uterine lining grows outside the uterus).

Treatment with Myfembree should not exceed 24 months because of the risk of ongoing bone loss that may not fully reverse after stopping the medication.

See full Relugolix, Estradiol, and Norethindrone drug information
Keep checking

Other Drugs & Grape

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

0Major
867Moderate
42Minor
1,920No known interaction
Moderate

867 interactions

Showing 60 of 867 moderate interactions — see all 867 on the Grape page.

Minor

42 interactions

No interaction 1,920 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

Keep exploring
Pharmacist Counseling Corner

Taking Grape and Relugolix, Estradiol, Norethindrone Acetate Together: Common Questions

Can you take Grape with Relugolix, Estradiol, Norethindrone Acetate?
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 Grape and Relugolix, Estradiol, Norethindrone Acetate?
Relugolix, Estradiol, Norethindrone Acetate belongs to more than one drug category, and 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 Grape and Relugolix, Estradiol, Norethindrone Acetate 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.