Drug Interaction Report

Estradiol and Omaveloxolone: Interaction Details

A pharmacist-reviewed analysis of the Estradiol and Omaveloxolone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Omaveloxolone

Skyclarys
+

Estradiol

Delestrogen
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 216 documented Estradiol interactions, 170 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

Reduced hormonal contraceptive exposure, reduced efficacy of contraceptive and an increased risk of breakthrough bleeding/contraceptive failure

Interaction Deep Dive

Avoid concomitant use of omaveloxolone (CYP3A4 inducer) with hormonal contraceptives1, as it may reduce hormonal contraceptive exposure and may reduce the efficacy of hormonal contraceptives. Also, may increase risk of breakthrough bleeding/contraceptive failure. Counsel women to use an alternative non-hormonal method of contraception or a back-up method when omaveloxolone are used with hormonal contraceptives and to continue back-up non-hormonal contraception for 28 days after discontinuing the omaveloxolone to ensure contraceptive reliability 2. Advise patients to avoid concomitant use with combined hormonal contraceptives (eg, pill, patch, ring), implants and progestin only pills 3.

Why it happens (mechanism)

Induction of CYP3A4-mediated metabolism by omaveloxolone

Common questions

Can I take Estradiol and Omaveloxolone together?

Reduced hormonal contraceptive exposure, reduced efficacy of contraceptive and an increased risk of breakthrough bleeding/contraceptive failure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Estradiol and Omaveloxolone interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Estradiol or Omaveloxolone need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (3)

  1. Product Information: FEMLYV orally disintegrating tablets, norethindrone acetate, ethinyl estradiol orally disintegrating tablets. Millicent U.S. Inc (per FDA), East Hanover, NJ, 2024. DailyMed
  2. Product Information: NuvaRing(R) vaginal ring, etonogestrel ethinyl estradiol vaginal ring. Organon & Co. (per FDA), Jersey City, NJ, 2024.
  3. Product Information: Skyclarys® oral capsules, omaveloxolone oral capsules. Biogen U.S. Corporation, Cambridge, MA, 2026. DailyMed
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Omaveloxolone

Keep reading about Omaveloxolone

All Omaveloxolone interactions (121)
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Estradiol

Keep reading about Estradiol

All Estradiol interactions (216) Estradiol drug information
Also serious with: Ensitrelvir Tranexamic Acid Fezolinetant Penicillin V Potassium
Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Omaveloxolone + Activated Charcoal Beer Siberian Cocklebur Wine Alkanna Alpine Ragwort Ashwagandha Black Cohosh + 63 more
Estradiol + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Aletris Alfalfa + 205 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.