Estradiol and Carbamazepine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Carbamazepine
Estradiol
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 and increased risk of breakthrough bleeding and/or contraceptive failure
Interaction Deep Dive
CarBAMazepine is a strong CYP3A4 inducer. Avoid concomitant use with hormonal contraceptives1. Concomitant use may significantly decrease exposure and contraceptive efficacy. In a study, concomitant use of a CYP3A4 inducer disproportionally increased unplanned pregnancy rate with oral and implanted contraceptives, but not with intrauterine devices or intravaginal rings; therefore, consider intrauterine or intravaginal routes if coadministration is required 4. Because breakthrough bleeding and significantly increased pregnancy rates have been reported with coadministration, consider an alternative to carBAMazepine, or employ alternative or backup contraceptive methods 2 during coadministration and for at least 28 days after discontinuation of carBAMazepine 3.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of hormonal contraceptives
Literature reports
6 reports — tap to read
a) Concomitant use of a CYP3A4 inducer with oral or implantable contraceptive products containing levonorgestrel (684 events) or etonogestrel/desogestrel (864 events) was associated with a disproportionately higher rate of unintended pregnancy compared to all other event types reported to the FDA Adverse Event Reporting System (FAERS) between 1971 and 2020 [levonorgestrel (14,504 total events); etonogestrel/desogestrel (9348 total events)]. When compared between CYP3A4 inducer exposure vs no exposure, cases of unintended pregnancy made up a significantly higher proportion of total events when levonorgestrel was administered orally (32.8% vs 10.5%) or as an implant (51.9% vs 11.9%), and a similar association was identified with implanted etonogestrel products (42.5% vs 13.1%). However, when contraceptives were administered as an intrauterine device (levonorgestrel, 10.3% vs 11.5%) or intravaginal ring (etonogestrel, 10.9% vs 8.7%), no significant associations were identified. Oral desogestrel (pro-drug of etonogestrel) in combination with ethynyl estradiol also was not significantly affected (11.8% vs 17.4%). Intrauterine and vaginal ring products may be preferred in lieu of oral and implantable contraceptive products in women concomitantly receiving CYP3A4 inducers 4.
b) In a study in healthy women (N=10 evaluable; 18 to 45 years) using an etonogestrel implant for 13 to 34 months, 3 weeks of coadministered carBAMazepine titrated up to 300 mg twice daily resulted in a significant median 61% decrease in etonogestrel levels from 158 picogram (pg)/mL (range, 127.9 to 347.3 pg/mL) to 50.8 pg/mL (range 39.4 to 202.3 pg/mL). In 8 women, the etonogestrel level was below the threshold for ovulatory suppression (less than 90 pg/mL) after carBAMazepine coadministration. There was no significant change in the number of ovarian follicle-like structures or endometrial thickness. No pregnancies were reported during the study period 5.
c) A randomized, open-label, five-group study concluded that carBAMazepine significantly decreased the mean AUC and Cmax values of oral contraceptives containing ethinyl estradiol and norethindrone. In two, 28-day cycles, five groups of female subjects received oral doses of ethinyl estradiol and norethindrone (Ortho-Novum 1/35(R)) alone in the first cycle and then in combination with topiramate or carBAMazepine during the second cycle. When carBAMazepine 600 mg/day was coadministered with ethinyl estradiol and norethindrone, a significant 42% and 58% decrease was observed in the mean AUC of both oral contraceptives, respectively, as was the mean Cmax by 19.2%. However, oral clearance significantly increased in both contraceptives by 127% and 69%, respectively. Coadministration of topiramate at daily doses for nonobese (50 mg, 100 mg, and 200 mg) and obese (200 mg) women resulted in a nonsignificant change in the AUC of ethinyl estradiol by -12%, +5%, -11% and -9%, respectively, when compared with the oral contraceptive alone. Norethindrone results were similar with plasma levels and AUC not significantly changed 6.
d) Concomitant administration of oral contraceptives with enzyme-inducing anticonvulsant agents, primarily PHENobarbital, phenytoin, carBAMazepine, or primidone, has been reported to result in an increased failure rate of contraception. The benzodiazepines and valproic acid have not been associated with increased failure rates in women receiving oral contraceptives. Increasing the dose of ethinyl estradiol or mestranol in oral contraceptives may diminish breakthrough bleeding and decrease the risk of conception. However, higher doses of estrogens may also increase the risk of vascular side effects, primarily in patients where enzyme induction does not occur. It is recommended that low doses of estrogen and progestin be given initially in patients receiving an enzyme inducing anticonvulsant; however, if unplanned pregnancy is a special concern, a moderate dose formulation (50 mcg ethinyl estradiol) should be considered. If breakthrough bleeding occurs with low-dose contraception, progressive increases in the dose of mestranol or its equivalent (up to 80 mcg) should be considered. If spotting occurs, it is suggested that the contraceptive not be discontinued, but rather that a traditional method of barrier contraception be initiated during the remainder of that cycle. Switching to a lower dose oral contraceptive is recommended if enzyme inducing anticonvulsants are discontinued in women receiving moderate or high-dose contraceptives 7.
e) CarBAMazepine reduced the AUC of ethinyl estradiol by 6% to 60% in 4 women taking carBAMazepine 300 to 600 mg daily within 8 to 12 weeks of initiation of therapy. Norgestrel AUCs were also significantly reduced to 29% to 57% of baseline. The authors suggest that breakthrough bleeding can be controlled for most women with use of oral contraceptives containing 80 to 100 mcg ethinyl estradiol 8.
f) Accidental pregnancy occurred in a 20-year-old patient with epilepsy who was using phenytoin 400 mg daily plus carBAMazepine 400 mg daily. The plasma concentration of levonorgestrel in this patient was very low (107 to 120 picograms (pg)/mL) when compared with controls (325 +/- 135 pg/mL). CarBAMazepine appears to decrease plasma levonorgestrel concentrations by enhancing the hepatic metabolism of the steroid via enzyme induction. Levonorgestrel should not be relied upon as the sole means of contraception in patients on anticonvulsant therapy 9.
Common questions
Can I take Estradiol and Carbamazepine together?
Reduced hormonal contraceptive exposure and increased risk of breakthrough bleeding and/or contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Estradiol and Carbamazepine 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 "established". Well documented — supported by controlled studies or strong clinical data.
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 Carbamazepine 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 (9)
- 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: EQUETRO oral extended-release capsules, carbamazepine oral extended-release capsules. Validus Pharmaceuticals LLC (per FDA), Parsippany, NJ, 2022. DailyMed
- Product Information: JADELLE(R) subdermal implants, levonorgestrel subdermal implants. Bayer Corp (per FDA), Pittsburgh, PA, 2016.
- Sunaga T, Cicali B, Schmidt S, et al: Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system. Contraception 2021; 103(4):222-224. PubMed
- Lazorwitz A, Davis A, Swartz M, et al: The effect of carbamazepine on etonogestrel concentrations in contraceptive implant users. Contraception 2017; 95(6):571-577. DOI
- 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
- Mattson RH, Cramer JA, Darney PD, et al: Use of oral contraceptives by women with epilepsy. JAMA 1986; 256:238-240. DOI
- Crawford P, Chadwick DJ, Martin C, et al: The interaction of phenytoin and carbamazepine with combined oral contraceptive steroids. Br J Clin Pharmacol 1990; 30:892-896. PubMed
- Haukkamaa M: Contraception by Norplant(R) subdermal capsules is not reliable in epileptic patients on anticonvulsant treatment. Contraception 1986; 33:559-565.
Keep reading about Carbamazepine
Keep reading about Estradiol
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