Drug & supplement interaction

Peony + Ethinyl Estradiol, Ethynodiol Diacetate

Ethinyl Estradiol, Ethynodiol Diacetate brand names: Demulen 1/35, Zovia 1/35, Demulen Compack, Demulen 1/50, Zovia 1/50, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Ethynodiol Diacetate falls into 4 drug categories that Peony can interact with; the most serious is rated moderate. Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions4
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Peony and Ethinyl Estradiol, Ethynodiol Diacetate

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

Why Are There 4 Interactions?

Peony interacts with whole categories of medication. Ethinyl Estradiol, Ethynodiol Diacetate falls into 4 of those categories, so it can interact with Peony in 4 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 4

Why this applies to Ethinyl Estradiol, Ethynodiol Diacetate

Ethinyl Estradiol, Ethynodiol Diacetate falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Peony interacts with.

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect 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

This combination pill (the brand names include Demulen, Zovia, and Kelnor) is partly cleared by a liver enzyme called CYP1A2. The idea here is that peony may gently slow that enzyme down. If it does, a little more of the estrogen part could stick around in your body, which in theory could nudge up estrogen-type side effects like nausea, breast tenderness, headaches, bloating, or spotting.

I want to be honest about how shaky this is. The signal comes only from lab and test-tube studies, not from real people, and the effect on the enzyme looked weak to moderate at best. So I would not lose sleep over it. Still, if you plan to use concentrated peony supplements regularly, run it by your pharmacist or doctor first rather than guessing.

References
  1. Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. PubMed
Moderate

ESTROGENS

2 of 4

Ethinyl Estradiol, Ethynodiol Diacetate also falls under ESTROGENS.

Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
In vitro and animal research shows that peony extract has estrogenic activity. Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.
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

This combination pill (Demulen, Zovia, Kelnor) contains a synthetic estrogen, ethinyl estradiol, plus a progestin. The concern with peony is purely theoretical. In lab dishes and animal studies, peony compounds like paeoniflorin seem to act a bit like estrogen at the body's estrogen receptors. On paper, that could add to your pill's estrogen effects or, in some cases, compete with them.

If anything happened, it might look like more estrogen-type side effects: breast tenderness, nausea, bloating, headaches, or mood changes. But honestly, this is only a 'might,' based on test-tube research, not real people. Small culinary or tea amounts are unlikely to matter; concentrated supplement doses are the bigger unknown. Before adding peony, just check with your pharmacist or doctor.

References
  1. Xu Y, Li X, Chen T, et al. Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice. Phytother Res. 2019;33(1):117-29. [RETRACTED].
Moderate

CONTRACEPTIVE DRUGS

3 of 4

Ethinyl Estradiol, Ethynodiol Diacetate also falls under CONTRACEPTIVE DRUGS.

Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
In vitro and animal research shows that peony extract has estrogenic activity. Concomitant use might also increase the risk for estrogen-related adverse effects.
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 with your birth control pill (the ethinyl estradiol and ethynodiol diacetate combo). Peony root contains plant compounds that, in lab and animal studies, seem to act a little like estrogen and can bump up against estrogen receptors. The worry is mostly theoretical, but in two directions: peony could in theory nudge how your hormones work, and it might add to estrogen-related effects.

In real life, that could mean a higher chance of things like nausea, breast tenderness, headaches, bloating, or breakthrough spotting. There's no strong human proof this actually happens, so don't panic. Just loop in your pharmacist or doctor before starting peony, and never stop your pill on your own, since reliable contraception matters here.

References
  1. Xu Y, Li X, Chen T, et al. Radix Paeoniae Alba increases serum estrogen level and up-regulates estrogen receptor expression in uterus and vagina of immature/ovariectomized mice. Phytother Res. 2019;33(1):117-29. [RETRACTED].
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

4 of 4

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

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect 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 birth control pill (ethinyl estradiol with ethynodiol diacetate) is broken down in the body partly by an enzyme called CYP3A4. Peony root may gently slow that enzyme down, at least in test tube studies. If that happened in real life, the estrogen part of your pill could build up a bit, which can mean more of the usual estrogen-related effects like nausea, breast tenderness, bloating, headaches, or mood changes.

Here is the reassuring part: this is purely a theoretical concern based on lab and animal research, not anything seen in actual people. The effect on the enzyme looked weak. Still, since you rely on this pill for pregnancy prevention and steady hormone levels, it is worth a quick chat with your pharmacist or doctor before adding peony.

References
  1. Wang W, Tian DD, Zheng B, et al. Peony-glycyrrhiza decoction, an herbal preparation, inhibits clozapine metabolism via cytochrome P450s, but not flavin-containing monooxygenase in in vitro models. Drug Metab Dispos 2015;43(7):1147-53. 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

Peony Also Interacts With Other Medications

Peony has 810 moderate known drug interactions in our database — the Ethinyl Estradiol, Ethynodiol Diacetate 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 Peony

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

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Ethynodiol Diacetate

This page covers Peony only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Ethynodiol Diacetate 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.

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

“The stakes here are pregnancy prevention, so I read this list with genuine seriousness. Ethinyl estradiol with ethynodiol diacetate (Zovia, Demulen, Kelnor) is a combined birth control pill, and the interactions that concern me most are the ones that can quietly weaken it.”

Reviewed by 2 · Jul 18, 2026

Open the Ethinyl Estradiol, Ethynodiol Diacetate interaction page

One more smart check

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

We hold 71 real supplement products containing Peony, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Peony. Your product may carry other ingredients that interact with Ethinyl Estradiol, Ethynodiol Diacetate too, on top of Peony — 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 Peony and Ethinyl Estradiol, Ethynodiol Diacetate 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 Peony
Top 25%

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

29 days ago today
Medication Ethinyl Estradiol, Ethynodiol Diacetate
Top half

#1,298 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 Peony

What is Peony?

Peony
  • Menstrual cramps and irregular periods
  • Muscle cramps and spasms
  • Anxiety and stress
  • Inflammation and pain
  • Polycystic ovary syndrome (PCOS)

Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formulas. Human evidence for most uses is limited or preliminary, so it should not replace proven treatments. Talk to your pharmacist or doctor before using it, especially if you are pregnant, breastfeeding, or taking other medicines.

Read the full Peony monograph & all interactions
Keep checking

Other Drugs & Peony

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

0Major
810Moderate
0Minor
2,019No known interaction
Moderate

810 interactions

Showing 60 of 810 moderate interactions — see all 810 on the Peony page.

No interaction 2,019 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 Peony and Ethinyl Estradiol, Ethynodiol Diacetate Together: Common Questions

Can you take Peony with Ethinyl Estradiol, Ethynodiol Diacetate?
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 4 interactions listed for Peony and Ethinyl Estradiol, Ethynodiol Diacetate?
Ethinyl Estradiol, Ethynodiol Diacetate belongs to more than one drug category, and Peony 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 Peony and Ethinyl Estradiol, Ethynodiol Diacetate 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.