Leflunomide and Ethinyl Estradiol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Leflunomide
Ethinyl Estradiol
No brand names on record
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.
What happens
Increased ethinyl estradiol exposure
Interaction Deep Dive
Concomitant use of leflunomide and ethinyl estradiol may increase the exposure of ethinyl estradiol. In a pharmacokinetic study, there was an increase in mean ethinyl estradiol Cmax and AUC(0 to 24) of 1.58- and 1.54-fold, respectively, following repeated doses of teriflunomide (active metabolite of leflunomide). Cautiously select the contraceptive method or dosage used in combination with leflunomide and choose an appropriate oral contraceptive if necessary1.
Why it happens (mechanism)
Altered metabolism of ethinyl estradiol
Literature reports
1 report — tap to read
a) Following repeated doses of teriflunomide (active metabolite of leflunomide), there was an increase in mean ethinyl estradiol Cmax and AUC(0 to 24) of 1.58- and 1.54-fold, respectively 1.
Common questions
Can I take Leflunomide and Ethinyl Estradiol together?
Increased ethinyl estradiol exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Leflunomide and Ethinyl Estradiol interaction?
It is rated moderate. Can be significant — usually manageable with 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 "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Leflunomide or Ethinyl Estradiol 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: ARAVA(R) oral tablets, leflunomide oral tablets. Sanofi-Aventis U.S. LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
Keep reading about Leflunomide
Keep reading about Ethinyl Estradiol
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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