Drug & supplement interaction

Licorice + Ethinyl Estradiol, Levonorgestrel

Ethinyl Estradiol, Levonorgestrel brand names: Levlite 28, Tri-Levlen 21, Tri-Levlen 28, Levlite, Trivora-28, and others.

Moderate Interaction
The bottom line Moderate

Ethinyl Estradiol, Levonorgestrel falls into 4 drug categories that Licorice can interact with; the most serious is rated moderate. Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.

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

Licorice and Ethinyl Estradiol, Levonorgestrel

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

Why Are There 4 Interactions?

Licorice interacts with whole categories of medication. Ethinyl Estradiol, Levonorgestrel falls into 4 of those categories, so it can interact with Licorice 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 3A4 (CYP3A4) SUBSTRATES

1 of 4

Why this applies to Ethinyl Estradiol, Levonorgestrel

Ethinyl Estradiol, Levonorgestrel falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group Licorice interacts with.

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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 deal with your birth control pill (the ethinyl estradiol and levonorgestrel combo). Both hormones are partly broken down by a liver enzyme called CYP3A4, and licorice can nudge that enzyme. The research is shaky and points in both directions, but one human study suggests certain licorice can speed up this enzyme a little. If that happens, your hormone levels could dip slightly, and in theory that could make the pill a touch less reliable.

To be honest, this is mostly theoretical and the effect seen was modest, so I wouldn't lose sleep over a cup of licorice tea. Concentrated licorice supplements taken daily for weeks are the bigger question mark. Before adding one, check with your pharmacist or doctor so your contraception stays dependable.

References
  1. Kent UM, Aviram M, Rosenblat M, Hollenberg PF. The licorice root derived isoflavan glabridin inhibits the activities of human cytochrome P450S 3A4, 2B6, and 2C9. Drug Metab Dispos 2002;30:709-15.. PubMed
  2. Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther 2006;316:1369-77. PubMed
  3. Tu, J. H., He, Y. J., Chen, Y., Fan, L., Zhang, W., Tan, Z. R., Huang, Y. F., Guo, D., Hu, D. L., Wang, D., and Hong-Hao Zhou. Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 2010;66(8):805-810. PubMed
  4. Li G, Simmler C, Chen L, et al. Cytochrome P450 inhibition by three licorice species and fourteen licorice constituents. Eur J Pharm Sci. 2017;109:182-190. PubMed
Moderate

ESTROGENS

2 of 4

Ethinyl Estradiol, Levonorgestrel also falls under ESTROGENS.

Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-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

Your pill pairs ethinyl estradiol (an estrogen) with levonorgestrel. The concern with licorice here is mostly on paper. Licorice plant compounds can act a little like estrogen in some lab tests and can block estrogen in others, so theoretically they could nudge your birth control's estrogen activity up or down. Honestly, this is based on test-tube and animal work, not real-world human studies, so I wouldn't lose sleep over it.

The bigger practical issue with regular (glycyrrhizin-containing) licorice is that it can raise blood pressure and lower potassium, and estrogen pills can already affect blood pressure too. Occasional licorice candy or tea is unlikely to matter, but daily concentrated supplements could. Please check with your pharmacist or doctor before making any changes.

References
  1. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50. PubMed
  2. Francini-Pesenti F, Puato M, Piccoli A, Brocadello F. Liquorice-induced hypokalaemia and water retention in the absence of hypertension. Phytother Res 2008;22:563-5. PubMed
Moderate

P-GLYCOPROTEIN SUBSTRATES

3 of 4

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

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
In vitro research shows that licorice can increase P-glycoprotein activity.
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 (the ethinyl estradiol and levonorgestrel combo): licorice contains compounds that, in lab studies, seem to rev up a transporter called P-glycoprotein. This pump can push some drugs back out of your gut before they're fully absorbed. In theory, that could mean a little less of your hormones gets into your bloodstream.

The honest truth is this is very weak evidence. It comes only from test-tube and animal work, not from real people, so we don't actually know if it makes any difference for you. Still, because reliable hormone levels matter for preventing pregnancy, it's worth a quick chat with your pharmacist before using concentrated licorice supplements regularly. A licorice cough drop now and then is unlikely to be a concern.

References
  1. Wang H, Dong L, Qu F, et al. Effects of glycyrrhizin on the pharmacokinetics of nobiletin in rats and its potential mechanism. Pharm Biol. 2020 Dec;58(1):352-356. PubMed
Minor

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

4 of 4

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

Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that licorice induces CYP1A2 enzymes.
Severity Minor 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, which combines ethinyl estradiol and levonorgestrel. Licorice may gently speed up a liver enzyme called CYP1A2, and in theory that could clear some of the hormone a little faster. If that happened, the pill might work slightly less well, which raises the worry of breakthrough bleeding or, in a worst case, reduced contraceptive protection.

That said, this is a very weak, theoretical concern based only on lab and test-tube data, not real people. Small amounts of licorice as candy or tea are unlikely to matter. Regular licorice in large or daily doses can also raise blood pressure and drop potassium, so check with your pharmacist or doctor before using concentrated supplements.

References
  1. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. 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

Licorice Also Interacts With Other Medications

Licorice has 976 moderate, 63 minor known drug interactions in our database — the Ethinyl Estradiol, Levonorgestrel 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 Licorice

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

From our Q&A

Questions About Licorice or Ethinyl Estradiol, Levonorgestrel

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

This page covers Licorice only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Ethinyl Estradiol, Levonorgestrel 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, Levonorgestrel interaction page

One more smart check

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

We hold 4,721 real supplement products containing Licorice, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Licorice. Your product may carry other ingredients that interact with Ethinyl Estradiol, Levonorgestrel too, on top of Licorice — 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 Licorice and Ethinyl Estradiol, Levonorgestrel 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 Licorice
Top 5%

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

29 days ago today
Medication Ethinyl Estradiol, Levonorgestrel
Top 25%

#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 Licorice

What is Licorice?

Licorice
  • Sore throat and cough
  • Heartburn and stomach upset
  • Mouth ulcers and digestive complaints
  • Inflammation
  • Traditional tonic/adrenal support

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, which can raise blood pressure and lower potassium when taken in large amounts or for a long time, so deglycyrrhizinated (DGL) products are often preferred. Talk to your pharmacist or doctor before using it, especially if you have high blood pressure, heart, or kidney problems.

Read the full Licorice monograph & all interactions
Keep checking

Other Drugs & Licorice

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

0Major
976Moderate
63Minor
1,790No known interaction
Moderate

976 interactions

Showing 60 of 976 moderate interactions — see all 976 on the Licorice page.

Minor

63 interactions

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

No interaction 1,790 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 Licorice and Ethinyl Estradiol, Levonorgestrel Together: Common Questions

Can you take Licorice with Ethinyl Estradiol, Levonorgestrel?
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 Licorice and Ethinyl Estradiol, Levonorgestrel?
Ethinyl Estradiol, Levonorgestrel belongs to more than one drug category, and Licorice 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 Licorice and Ethinyl Estradiol, Levonorgestrel 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.