Drug & supplement interaction

Grapefruit + Ethinyl Estradiol, Drospirenone

Ethinyl Estradiol, Drospirenone brand name: Yaz.

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

Ethinyl Estradiol, Drospirenone falls into 4 drug categories that Grapefruit can interact with; the most serious is rated major. Grapefruit juice can increase blood levels of estrogens, potentially increasing the effects and adverse effects of estrogens.

Read the full interaction report
SeverityMajor
LikelihoodProbable
Interactions4
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

Grapefruit and Ethinyl Estradiol, Drospirenone

These two interact in 4 distinct ways. Each one is explained separately below.

Why Are There 4 Interactions?

Grapefruit interacts with whole categories of medication. Ethinyl Estradiol, Drospirenone falls into 4 of those categories, so it can interact with Grapefruit in 4 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

ESTROGENS

1 of 4

Why this applies to Ethinyl Estradiol, Drospirenone

Ethinyl Estradiol, Drospirenone falls under ESTROGENS — the group Grapefruit interacts with.

Grapefruit juice can increase blood levels of estrogens, potentially increasing the effects and adverse effects of estrogens.
Clinical research shows that grapefruit increases the levels of endogenous and exogenous estrogens by inhibiting cytochrome P450 3A4 (CYP3A4) enzymes. Grapefruit juice increases exogenously administered 17-beta-estradiol by about 20% in females without ovaries and ethinyl-estradiol in healthy females.
Severity Major Likelihood Probable Evidence B

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the short version with your Yaz: grapefruit can block an enzyme in your gut and liver called CYP3A4, and that same enzyme helps break down the estrogen part of your pill (ethinyl estradiol). When grapefruit slows that breakdown, a little more estrogen can stay in your system. Studies have measured roughly a 20% bump in estrogen levels.

So this isn't about your pill working less well, it's about slightly stronger estrogen effects. That could mean more nausea, breast tenderness, bloating, or headaches for some people. The evidence here is real but modest, and an occasional grapefruit is different from drinking the juice every day. If you enjoy grapefruit regularly, just run it by your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41-7.
  2. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155-63.
  3. Monroe KR, Murphy SP, Kolonel LN, Pike MC. Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Mutliethnic Cohort Study. Br J Cancer 2007;97:440-5.
  4. Fingerova, H., Oborna, I., Petrova, P., Budikova, M., and Jezdinsky, J. [Does grapefruit juice increase the bioavailability of orally administered sex steroids?]. Ceska.Gynekol. 2003;68(2):117-121.
Major

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 4

Ethinyl Estradiol, Drospirenone also falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES.

Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours. Grapefruit's ability to inhibit CYP3A4 has even been harnessed to intentionally increase levels of venetoclax, which is metabolized by CYP3A4, in an elderly patient with acute myeloid leukemia who could not afford full dose venetoclax. The lower dose of venetoclax in combination with grapefruit juice resulted in serum levels of venetoclax in the therapeutic reference range of full dose venetoclax and positive treatment outcomes for the patient.
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the simple version with Yaz (ethinyl estradiol plus drospirenone). The estrogen part of your pill is broken down by an enzyme in your gut and liver called CYP3A4. Grapefruit slows that enzyme down, so a bit more estrogen can stay in your system than usual. In plain terms, grapefruit doesn't weaken your birth control, it can nudge the hormone levels up a little.

What might that feel like? Possibly more of the typical estrogen-related effects, like nausea, breast tenderness, bloating, or headaches. An occasional glass of juice or a few grapefruit slices is unlikely to cause trouble, but drinking it regularly is where I'd pause. Since drospirenone can also raise potassium, it's worth a quick chat with your pharmacist or doctor about your routine.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999;66:118-27. DOI
  2. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998;64:477-83. PubMed
  3. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9. PubMed
  4. Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002;58:45-53. PubMed
  5. Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001;56:799-803. PubMed
  6. Charbit, B., Becquemont, L., Lepere, B., Peytavin, G., and Funck-Brentano, C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther 2002;72(5):514-523. PubMed
  7. Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41. PubMed
  8. Bailey DG. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. J Clin Pharm Ther. 2017 Apr;42(2):125-27. PubMed
  9. Mouly S, Lloret-Linares C, Sellire PO, Sene D, Bergmann JF. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res. 2017 Apr;118:82-92. PubMed
  10. Loretz C, Ho MD, Alam N, Mitchell W, Li AP. Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial f
  11. Long Z, Ruan M, Wu W, Zeng Q, Li Q, Huang Z. The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report. Front Oncol 2022;12:912696. PubMed
Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

3 of 4

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

Theoretically, grapefruit juice might increase levels of drugs metabolized by CYP1A2.
In vitro research suggests that grapefruit juice might inhibit CYP1A2 enzymes. So far, this interaction 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 short version on Yaz (ethinyl estradiol plus drospirenone) and grapefruit. The concern on file is that grapefruit might block a liver enzyme called CYP1A2, which helps process the estrogen part of your pill. In theory, slowing that breakdown could let estrogen levels drift a little higher, which might mean more of the usual estrogen side effects like nausea, breast tenderness, bloating, or headaches.

But I want to be honest about how thin this evidence is. It comes only from lab (test-tube) studies, and this effect has never actually been reported in people. Normal amounts of grapefruit you'd eat for breakfast are very unlikely to cause a problem. If you eat grapefruit often or drink the juice daily, just mention it to your pharmacist or doctor so they can reassure you.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
Minor

P-GLYCOPROTEIN SUBSTRATES

4 of 4

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

Grapefruit juice does not seem to affect renal P-glycoprotein (P-gp). Theoretically, it might inhibit intestinal P-gp, but evidence is conflicting.
While most in vitro research shows that grapefruit products inhibit P-gp,, research in humans is less clear. Two small clinical studies in healthy adults using digoxin as a probe substrate show that grapefruit juice does not inhibit P-gp in the kidneys. It is unclear whether this applies to intestinal P-gp, for which digoxin is not considered to be a sensitive probe. Grapefruit juice has been shown to reduce levels of fexofenadine, and increase levels of quinidine. However, as both of these drugs are also substrates of other enzymes and transporters, it is unclear what role, if any, intestinal P-gp has in these findings.
Severity Minor 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

If you're taking Yaz and wondering about grapefruit, here's the honest picture. The interaction on file looks at grapefruit's effect on a transporter called P-glycoprotein. In real people, the evidence that grapefruit meaningfully blocks this transporter is weak and conflicting, and the rating here is minor. Yaz isn't a prodrug, so it doesn't need to be activated first.

Practically speaking, eating or drinking grapefruit in normal amounts is unlikely to noticeably change how your birth control works or cause new side effects. I wouldn't expect a real impact on its reliability. That said, since this is your contraception, it's worth a quick check with your pharmacist or doctor if you eat grapefruit regularly, just to be sure nothing else in your routine adds up.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Soldner A, Christians U, Susanto M, et al. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res 1999;16:478-85. PubMed
  2. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999;48:829-38. PubMed
  3. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  4. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  5. Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2001;70:311-6. DOI
  6. Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 2002;71:11-20. PubMed
  7. Parker RB, Yates CR, Soberman JE, Laizure SC. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 2003;23:979-87. PubMed
  8. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  9. Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005;77:170-7. PubMed
  10. Min, D. I., Ku, Y. M., Geraets, D. R., and Lee, H. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol 1996;36(5):469-476. PubMed
  11. Jia Y, Liu J, Xu J. Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide. Xenobiotica. 2017 Apr 16:1-5. PubMed
  12. Guideline on the investigation of drug interactions. CPMP/EWP/560/95/Rev. 1 Corr. 2. European Medicines Agency, 2015. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions-revision-1_en.pdf (As
  13. Piscitelli J, Nikanjam M, Capparelli EV, et al. Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach. Ther Drug Monit 2023;45(4):539-545. 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

Grapefruit Also Interacts With Other Medications

Grapefruit has 775 major, 151 moderate, 63 minor known drug interactions in our database — the Ethinyl Estradiol, Drospirenone one above is among them. If you take anything else, check it against the full list below.

Major 775 Moderate 151 Minor 63 No known interaction 1,841 (incl. Ethinyl Estradiol, Drospirenone)
Taking anything else?

Check Another of Your Medications Against Grapefruit

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

From our Q&A

Questions About Grapefruit or Ethinyl Estradiol, Drospirenone

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Grapefruit or Ethinyl Estradiol, Drospirenone, 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 Ethinyl Estradiol, Drospirenone

This page covers Grapefruit only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Drospirenone page lists 245 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 6 major · 200 moderate · 39 minor.

Open the Ethinyl Estradiol, Drospirenone interaction page

One more smart check

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

We hold 1,144 real supplement products containing Grapefruit, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Grapefruit. Your product may carry other ingredients that interact with Ethinyl Estradiol, Drospirenone too, on top of Grapefruit — 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 Grapefruit and Ethinyl Estradiol, Drospirenone 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 Grapefruit
Top 10%

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

29 days ago today
Medication Ethinyl Estradiol, Drospirenone
Top 5%

#116 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 Grapefruit

What is Grapefruit?

Grapefruit
  • Source of vitamin C
  • Digestive complaints
  • Antimicrobial (seed extract)
  • Weight management
  • Skin and cosmetic uses

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription medicines, so anyone taking medication should check with a pharmacist or doctor before consuming it regularly.

Read the full Grapefruit monograph & all interactions
Keep checking

Other Drugs & Grapefruit

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

775Major
151Moderate
63Minor
1,840No known interaction
775 Major 151 Moderate 63 Minor 1,840 No interaction
Major

775 interactions

Showing 60 of 775 major interactions — see all 775 on the Grapefruit page.

Moderate

151 interactions

Showing 60 of 151 moderate interactions — see all 151 on the Grapefruit page.

Minor

63 interactions

Showing 60 of 63 minor interactions — see all 63 on the Grapefruit page.

No interaction 1,840 drugs checked — show the list

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

Showing the 60 most looked-up of 1,840 medications checked with no known interaction — see the full Grapefruit list.

See the full Grapefruit interactions page
See every supplement checked against Ethinyl Estradiol, Drospirenone, 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
Grapefruit monograph › Uses, safety, and every drug interaction in one place Ethinyl Estradiol, Drospirenone supplement interactions › Every supplement checked against Ethinyl Estradiol, Drospirenone, 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 Grapefruit and Ethinyl Estradiol, Drospirenone Together: Common Questions

Can you take Grapefruit with Ethinyl Estradiol, Drospirenone?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 4 interactions listed for Grapefruit and Ethinyl Estradiol, Drospirenone?
Ethinyl Estradiol, Drospirenone belongs to more than one drug category, and Grapefruit 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 Grapefruit and Ethinyl Estradiol, Drospirenone interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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