Drug & supplement interaction

Syrian Rue + Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol brand name: Annovera.

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

Segesterone Acetate, Ethinyl Estradiol falls into 2 drug categories that Syrian Rue can interact with; the most serious is rated moderate. Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.

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

Syrian Rue and Segesterone Acetate, Ethinyl Estradiol

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

Why Are There 2 Interactions?

Syrian Rue interacts with whole categories of medication. Segesterone Acetate, Ethinyl Estradiol falls into 2 of those categories, so it can interact with Syrian Rue in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

HEPATOTOXIC DRUGS

1 of 2

Why this applies to Segesterone Acetate, Ethinyl Estradiol

Segesterone Acetate, Ethinyl Estradiol falls under HEPATOTOXIC DRUGS — the group Syrian Rue interacts with.

Theoretically, high doses of Syrian rue might increase the risk of liver damage when taken with hepatotoxic drugs.
Cases of hepatotoxicity and hepatic failure have been reported in patients who ingested a large quantity (up to 100 grams) of Syrian rue seeds.
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 thing to know about Annovera (the segesterone and ethinyl estradiol vaginal ring): like all estrogen-containing birth control, it's processed by your liver and can occasionally stress it. Syrian Rue isn't tied to this product through a specific enzyme problem. Instead, the concern is simpler: in rare reports, people who swallowed very large amounts of the seeds (we're talking up to 100 grams) developed liver injury. Pile that on top of a hormone medication your liver already handles, and you could, in theory, raise the strain on your liver.

This is a theoretical worry, not something proven in real patients combining the two. Normal incidental exposure is unlikely to matter, but concentrated seed doses are genuinely risky on their own. Watch for yellowing skin or eyes, dark urine, or belly pain, and please check with your pharmacist or doctor before using Syrian Rue.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Yuruktumen, A., Karaduman, S., Bengi, F., and Fowler, J. Syrian rue tea: a recipe for disaster. Clin Toxicol (Phila) 2008;46(8):749-752. PubMed
  2. Berdai MA, Labib S, Harandou M. Peganum harmala L. Intoxication in a Pregnant Woman. Case Rep Emerg Med 2014;2014:783236.
  3. Ghizlane EA, Manal M, Ines HA, et al. Fatal poisoning of pregnant women by peganum harmala L.: a case reports. Ann Med Surg (Lond) 2021;68:102649. PubMed
  4. Durmaz Çelik N, Ger Akarsu F, Ozkan S, Özdemir AÖ, Aykac Ö, Memmedova F. Herbal teas can be harmful: a case of Peganum harmala induced coma in a patient with Parkinson's disease. Neurocase 2021;27(2):117-119.
Moderate

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

2 of 2

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

Theoretically, Syrian rue might increase the levels and clinical effects of drugs metabolized by CYP3A4.
Syrian rue contains beta-carboline alkaloids, including harmine, harmol, and harmane. In vitro research suggests that these beta-carboline alkaloids competitively inhibit CYP3A4 enzymes.
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

Annovera is a vaginal ring that releases two active hormones, segesterone acetate and ethinyl estradiol. The estrogen part is handled by a liver enzyme called CYP3A4. Lab studies suggest the harmala alkaloids in Syrian Rue can slow that enzyme down. In theory, that could let estrogen build up a bit higher than usual, which sometimes shows up as nausea, breast tenderness, headaches, bloating, or spotting.

I want to be honest here: this is a theoretical concern based only on test-tube research, not real human cases, so the actual risk is unclear. Still, Syrian Rue carries its own toxicity risks and isn't recommended for self-treatment. Please check with your pharmacist or doctor before pairing the two rather than changing anything on your own.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Zhao, T., He, Y. Q., Wang, J., Ding, K. M., Wang, C. H., and Wang, Z. T. Inhibition of human cytochrome P450 enzymes 3A4 and 2D6 by β-carboline alkaloids, harmine derivatives. Phytother Res 2011;25(11):1671-1677.

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

Syrian Rue Also Interacts With Other Medications

Syrian Rue has 1,121 moderate known drug interactions in our database — the Segesterone Acetate, Ethinyl Estradiol one above is among them. If you take anything else, check it against the full list below.

Moderate 1,121 No known interaction 1,709 (incl. Segesterone Acetate, Ethinyl Estradiol)
Taking anything else?

Check Another of Your Medications Against Syrian Rue

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

Everything else you take

See Every Supplement That Interacts With Segesterone Acetate, Ethinyl Estradiol

This page covers Syrian Rue only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Segesterone Acetate, Ethinyl Estradiol page lists 229 supplements it has a documented interaction with, worst first, each one explained.

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

By severity: 5 major · 193 moderate · 31 minor.

From our pharmacist’s overview on the Segesterone Acetate, Ethinyl Estradiol page

“St. John's wort is the interaction I would explain first to anyone using Annovera (segesterone acetate with ethinyl estradiol, a vaginal ring for birth control).”

Reviewed by 2 · Jul 18, 2026

Open the Segesterone Acetate, Ethinyl Estradiol interaction page

How much people look this up

Where Syrian Rue and Segesterone Acetate, Ethinyl Estradiol 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 Syrian Rue
Steady interest

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

29 days ago today
Medication Segesterone Acetate, Ethinyl Estradiol
Top 25%

#419 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 Syrian Rue

What is Syrian Rue?

  • Traditional remedy for digestive complaints
  • Used as a sedative or for mood
  • Antimicrobial and antiparasitic folk use
  • Used as a dye and incense
  • Recreational psychoactive use

Syrian Rue (Peganum harmala) is a traditional plant whose seeds contain potent compounds called harmala alkaloids, including MAO-inhibiting harmine and harmaline. There is little reliable human evidence that it safely treats any condition, and it carries real risks of toxicity, so it is not recommended for self-treatment. Talk to a pharmacist or doctor before considering it.

Read the full Syrian Rue monograph & all interactions
Keep checking

Other Drugs & Syrian Rue

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

0Major
1,121Moderate
0Minor
1,708No known interaction
1,121 Moderate 1,708 No interaction
Moderate

1,121 interactions

Showing 60 of 1,121 moderate interactions — see all 1,121 on the Syrian Rue page.

No interaction 1,708 drugs checked — show the list

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

Showing the 60 most looked-up of 1,708 medications checked with no known interaction — see the full Syrian Rue list.

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

Can you take Syrian Rue with Segesterone Acetate, Ethinyl Estradiol?
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 Syrian Rue and Segesterone Acetate, Ethinyl Estradiol?
Segesterone Acetate, Ethinyl Estradiol belongs to more than one drug category, and Syrian Rue 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 Syrian Rue and Segesterone Acetate, Ethinyl Estradiol 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.