Drug & supplement interaction

Sage + 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 3 drug categories that Sage can interact with; the most serious is rated moderate. Theoretically, sage might increase levels of drugs transported by P-glycoprotein.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions3
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sage and Ethinyl Estradiol, Levonorgestrel

These two interact in 3 distinct ways. Each one is explained separately below.

Why Are There 3 Interactions?

Sage interacts with whole categories of medication. Ethinyl Estradiol, Levonorgestrel falls into 3 of those categories, so it can interact with Sage in 3 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

P-GLYCOPROTEIN SUBSTRATES

1 of 3

Why this applies to Ethinyl Estradiol, Levonorgestrel

Ethinyl Estradiol, Levonorgestrel falls under P-GLYCOPROTEIN SUBSTRATES — the group Sage interacts with.

Theoretically, sage might increase levels of drugs transported by P-glycoprotein.
In vitro research suggests that common sage (Salvia officinalis) can inhibit the multi-drug transporter protein, P-glycoprotein. 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

Here's the short version for your birth control pill (the combo of ethinyl estradiol and levonorgestrel). In lab dishes, sage seems to block a tiny pump in your gut called P-glycoprotein that helps move certain drugs in and out. If that pump slows down, a bit more of your hormone pill could in theory stay in your body. That isn't the same as it weakening your birth control, it would lean toward slightly higher hormone levels, which might mean more of the usual things like nausea, breast tenderness, or spotting.

Honestly though, this has only been seen in test tubes, never in real people, and a sprinkle of sage in your cooking is no concern at all. If you take concentrated sage extracts or the essential oil regularly, just mention it to your pharmacist or doctor.

References
  1. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 3

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

Theoretically, sage might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro evidence suggests that aqueous extracts of sage can inhibit CYP3A4. 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

Your birth control pill (the ethinyl estradiol and levonorgestrel combo) is partly broken down by a liver enzyme called CYP3A4. In lab dishes, water-based sage extracts seemed to slow that enzyme down a bit. In theory, that could let a little more hormone hang around in your body, which might bump up typical side effects like nausea, breast tenderness, headaches, or spotting.

Here's the honest part: this has only been seen in test-tube studies, never in real people, so I wouldn't lose sleep over it. Normal cooking amounts of sage are very unlikely to matter. Concentrated sage extracts or the essential oil are a different story and deserve more caution. If you plan to use sage supplements regularly, just run it by your pharmacist or doctor first.

References
  1. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  2. Hellum, B. H. and Nilsen, O. G. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. 2008;102(5):466-475.
Moderate

ESTROGENS

3 of 3

Ethinyl Estradiol, Levonorgestrel also falls under ESTROGENS.

Theoretically, sage might interfere with hormone therapy.
In vitro evidence suggests that geraniol, a constituent of Spanish sage (Salvia lavandulaefolia), exerts estrogenic activity. The clinical significance of this effect is unclear.
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 combines two hormones, ethinyl estradiol (an estrogen) and levonorgestrel (a progestin), to prevent pregnancy. The concern here is pretty mild. In test tube studies, a compound found in Spanish sage seemed to act a little like estrogen itself. On paper, that means concentrated sage could, in theory, add to or nudge your body's hormone signals. But honestly, nobody has shown this actually matters in real people, and it does not appear to make your pill less effective.

The amount of sage you'd get from cooking is not something I'd worry about at all. If you're thinking about taking strong sage extracts or the essential oil regularly, just run it by your pharmacist or doctor first.

References
  1. Perry, N. S., Houghton, P. J., Sampson, J., Theobald, A. E., Hart, S., Lis-Balchin, M., Hoult, J. R., Evans, P., Jenner, P., Milligan, S., and Perry, E. K. In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's diseas

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

Sage Also Interacts With Other Medications

Sage has 1,295 moderate 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 Sage

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

Everything else you take

See Every Supplement That Interacts With Ethinyl Estradiol, Levonorgestrel

This page covers Sage 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 Sage as Part of a Dietary Supplement Product? Check It for Interactions

We hold 718 real supplement products containing Sage, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sage. Your product may carry other ingredients that interact with Ethinyl Estradiol, Levonorgestrel too, on top of Sage — 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 Sage 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 Sage
Top 25%

#265 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 Sage

What is Sage?

Sage
  • Sore throat and mouth irritation
  • Digestive upset
  • Excessive sweating
  • Memory and thinking
  • Menopause symptoms (hot flashes)
  • General antioxidant support

Sage is a common kitchen herb that is generally safe in food amounts and is traditionally used for sore throats, digestion, sweating, and memory. Some early research is encouraging for sore throat and menopausal hot flashes, but most uses are not well proven. Concentrated extracts and the essential oil should be used carefully because high doses contain a compound called thujone, which can be harmful.

Read the full Sage monograph & all interactions
Keep checking

Other Drugs & Sage

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

0Major
1,295Moderate
0Minor
1,534No known interaction
Moderate

1,295 interactions

Showing 60 of 1,295 moderate interactions — see all 1,295 on the Sage page.

No interaction 1,534 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 Sage and Ethinyl Estradiol, Levonorgestrel Together: Common Questions

Can you take Sage 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 3 interactions listed for Sage and Ethinyl Estradiol, Levonorgestrel?
Ethinyl Estradiol, Levonorgestrel belongs to more than one drug category, and Sage 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 Sage 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.