Topiramate and Estradiol Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Topiramate
Estradiol Topical
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
Reduced hormonal contraceptive exposure, reduced contraceptive efficacy and an increased risk of breakthrough bleeding/contraceptive failure
Interaction Deep Dive
Avoid concomitant use of topiramate (CYP3A4 inducer) and combination oral contraceptives1. It may result in decreased contraceptive efficacy and increased breakthrough bleeding, especially with contraceptives at doses greater than 200 mg/day. Advise patients to report any changes in their bleeding patterns if topiramate is used concomitantly with estrogen-containing or progestin only contraceptives 5. Patients should use additional contraception or an alternate nonhormonal contraceptive method 47 during coadministration and for at least 28 days after discontinuation of topiramate 2.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of hormonal contraceptive
Literature reports
4 reports — tap to read
a) Topiramate significantly decreased serum etonogestrel concentrations following 6 weeks of concomitant use in a prospective, non-inferiority study of healthy females of reproductive potential (median age, 25.3 years) who had received etonogestrel implants continuously for a median duration of 24 months (range, 12 to 36 months) (n=32 evaluable). Median serum etonogestrel concentrations were 142 picogram (pg)/mL at baseline and 105 pg/mL at visit 4 (end of the sixth week topiramate titration schedule). Mean percent change in serum etonogestrel concentration was -37.3% at visit 2 (end of third week of topiramate titration), -45.4% at visit 3 (end of fourth week of topiramate titration), and -66.8% at visit 4. Serum etonogestrel concentrations significantly decreased with increasing topiramate therapy. Excluding 1 participant with a serum etonogestrel concentration less than 90 pg/mL at baseline, 30.8% of patients had a serum etonogestrel concentration of less than 90 pg/mL at the maximum topiramate dose for visit 4. Topiramate was titrated over 6 weeks to a maximum dose of 200 mg twice daily by the final week. Patients receiving other CYP3A4 inducers or inhibitors were excluded 8.
b) A randomized, open-label, 5-group study in healthy volunteers concluded that topiramate doses less than or equal to 200 mg/day do not interact with oral contraceptives containing ethinyl estradiol and norethindrone. In two 28-day cycles, 5 groups of female subjects received oral doses of ethinyl estradiol/norethindrone (Ortho-Novum(R) 1/35) alone in the first cycle and then in combination with topiramate or carBAMazepine during the second cycle. Coadministration of daily topiramate in nonobese (50 mg, n=11; 100 mg, n=10; 200 mg, n=12) and obese (BMI 30 to 35; n=12; topiramate 200 mg) women resulted in nonsignificant changes in the AUC of ethinyl estradiol and nonsignificant changes in the AUC and plasma concentrations of norethindrone compared with the contraceptive alone. When carBAMazepine 600 mg/day was coadministered with ethinyl estradiol/norethindrone (n=10), significant decrease in AUC of each drug was observed; 42% and 58%, respectively. CarBAMazepine increased oral clearance in both contraceptives by 127% and 69%, respectively 3.
c) In a study of 12 women with epilepsy who were receiving stable valproic acid monotherapy and oral contraception with ethinyl estradiol 35 mcg/norethindrone 1 mg (21 days on/7 days off), the coadministration of topiramate (200 to 800 mg/day) for four 28-day cycles significantly decreased systemic exposure to ethinyl estradiol. Starting on the first 3 days of cycle 2 through cycle 4, topiramate 100 mg, 200 mg, and 400 mg were given twice daily, respectively. Although, the addition of topiramate did not change the norethindrone pharmacokinetic parameters, the mean AUC of ethinyl estradiol was decreased by 18%, 21%, and 30% with daily topiramate doses of 200 mg, 400 mg, and 800 mg, respectively, in cycles 2 through 4 compared with cycle 1 (control cycle) and mean serum clearance (CL/F) of ethinyl estradiol was 14.7% to 33% higher. It is suggested that the modest effect of topiramate on ethinyl estradiol pharmacokinetics may be due to topiramate being a weak inducer of cytochrome P450 9.
d) An expert Working Group that was convened by the WHO in 2008 to revise the third edition of the Medical Eligibility Criteria for Contraceptive Use recommended patients avoid the concomitant use of topiramate with combined oral contraceptives, the transdermal patch, the vaginal ring, or progestin-only pills due to the risk of decreased contraceptive efficacy 10.
Common questions
Can I take Topiramate and Estradiol Topical together?
Reduced hormonal contraceptive exposure, reduced contraceptive efficacy and an increased risk of breakthrough bleeding/contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Topiramate and Estradiol Topical interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
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 Topiramate or Estradiol Topical 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 (10)
- Product Information: FEMLYV orally disintegrating tablets, norethindrone acetate, ethinyl estradiol orally disintegrating tablets. Millicent U.S. Inc (per FDA), East Hanover, NJ, 2024. DailyMed
- Product Information: JADELLE(R) subdermal implants, levonorgestrel subdermal implants. Bayer Corp (per FDA), Pittsburgh, PA, 2016.
- Doose DR, Wang SS, Padmanabhan M, et al: Effect of topiramate or carbamazepine on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in healthy obese and nonobese female subjects. Epilepsia 2003; 44(4):540-549. PubMed
- Product Information: NuvaRing(R) vaginal ring, etonogestrel ethinyl estradiol vaginal ring. Organon & Co. (per FDA), Jersey City, NJ, 2024.
- Product Information: TOPAMAX(R) oral tablets, oral sprinkle capsules, topiramate oral tablets, oral sprinkle capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2023. DailyMed
- Product Information: NEXPLANON(R) subdermal implant, etonogestrel subdermal implant. Organon & Co (per FDA), Jersey City, NJ, 2023.
- Product Information: DEPO-PROVERA(R) CI IM injection suspension, medroxyprogesterone acetate IM injection suspension. Pharmacia & Upjohn Company (per FDA), New York, NY, 2011.
- Lazorwitz A, Pena M, Sheeder J, et al: Effect of topiramate on serum etonogestrel concentrations among contraceptive implant users. Obstet Gynecol 2022; 139(4):579-587. PubMed
- Rosenfeld WE, Doose DR, Walker SA, et al: Effect of topiramate on the pharmacokinetics of an oral contraceptive containing norethindrone and ethinyl estradiol in patients with epilepsy. Epilepsia 1997; 38:317-323. DOI
- Gaffield ME, Culwell KR, & Lee CR: The use of hormonal contraception among women taking anticonvulsant therapy. Contraception 2011; 83(1):16-29. PubMed
Keep reading about Topiramate
Keep reading about Estradiol Topical
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