Lamotrigine and Estradiol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lamotrigine
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 lamoTRIgine exposure and an increased risk of seizures
Interaction Deep Dive
Concomitant use of lamoTRIgine with estrogen-containing oral contraceptives (OCs) have been shown to significantly reduce lamoTRIgine exposure (eg, possible seizures). Therefore, carefully monitor and adjust lamoTRIgine doses in women who choose estrogen-containing hormonal contraception. In women already taking OCs and not taking other enzyme inducers, the maintenance dose of lamoTRIgine may need to be increased by 2-fold. During maintenance, if no enzyme inducers are coadministered, and OCs need to be started, lamoTRIgine may need to be doubled to maintain plasma levels. Dose increases should begin while the OC is introduced and continue, based on clinical response (no more rapidly than 50 to 100 mg/day every week). Dose increases should not exceed the recommended rate, unless lamoTRIgine plasma levels or clinical response support larger increases. Gradual transient increases in lamoTRIgine plasma levels may occur during the week of inactive hormonal preparation (pill-free week) and these increases will be greater if dose increases are made in the days before or during the week of inactive hormonal preparation. Dose adjustments to the overall maintenance dose may be necessary and dose adjustments limited to the pill-free week are not recommended. When starting lamoTRIgine in women taking OCs, no lamoTRIgine dose change is needed. If OCs are stopped in women not taking other enzyme inducers, reduce lamoTRIgine by up to 50%, tapering no more than 25% per week over 2 weeks unless plasma levels or symptoms suggest otherwise. No change is needed if OCs are stopped while women are taking other enzyme inducers1.
Why it happens (mechanism)
Induction of lamoTRIgine glucuronidation by combination contraceptive
Literature reports
4 reports — tap to read
a) Evidence from a double-blind, placebo-controlled trial involving 7 women with epilepsy suggests that oral contraceptives induce the metabolism of lamoTRIgine. All patients were treated with lamoTRIgine monotherapy and taking combination oral contraceptives at study enrollment. They were then allocated in a crossover fashion to receive either placebo or contraceptive (ethinyl estradiol 35 mcg/norgestimate 250 mcg) over 4 periods (21 days of treatment followed by a 7-day pause). Steady-state blood samples were collected as trough levels (just prior to the next dose) and urine samples were collected between the evening and morning doses. Mean lamoTRIgine plasma concentrations increased by 84% (95% CI, 45% to 134%) after placebo for 21 days compared with oral contraceptive treatment for 21 days. Urine excretion of lamoTRIgine metabolites, measured as the N-2-glucuronide/lamoTRIgine ratio, was decreased by 31% (95% CI, -20% to 61%) when placebo was taken instead of oral contraceptive. Seizures occurred in 3 patients during oral contraceptive therapy while no seizures occurred during placebo therapy. The mechanism of the interaction is likely the induction of glucuronidation pathways involved in the metabolism of lamoTRIgine and ethinyl estradiol 2.
b) Several cases in which oral contraceptives changed the plasma levels of lamoTRIgine as well as the patient's clinical condition have been reported. Five patients who were seizure-free (1 with epilepsy, 2 with complex partial seizures, and 2 with absence epilepsy) had decreased lamoTRIgine serum concentrations after oral contraceptives were initiated. Two other patients, 1 with simple partial seizures and 1 with complex partial seizures, had discontinued their oral contraceptives. Plasma levels of lamoTRIgine in these 2 patients had increased significantly as well. Oral contraceptives reduce the plasma levels of lamoTRIgine 41% to 64% (mean, 49%). As a result, seizure control deteriorated when oral contraceptives were added, or side effects occurred when oral contraceptives were discontinued. These effects were independent of whether the oral contraceptives contained desogestrel, ethinyl estradiol, or norethindrone. The author concludes that there is a need for careful monitoring and adjustment of the lamoTRIgine doses in women with epilepsy who use combination contraceptives 3.
c) LamoTRIgine plasma levels are reduced by greater than 50% during oral contraceptive coadministration. A retrospective study evaluated 52 women, 22 who used oral contraceptives and 30 who did not. The mean lamoTRIgine dose was 349 mg/day among women taking oral contraceptives and 327 mg/day among those who did not. Mean plasma level of lamoTRIgine was 13 mcmol/L in patients on oral contraceptives and 28 mcmol/L in patients without oral contraceptives (p less than 0.0001). Oral contraceptives markedly decrease plasma concentrations of lamoTRIgine 4.
d) In a study of 16 female volunteers, estrogen-containing oral contraceptive (ethinyl estradiol 30 mcg/levonorgestrel 150 mcg) increased the apparent clearance of lamoTRIgine 300 mg/day by approximately 2-fold with a mean decrease in AUC of 52% and in Cmax of 39%. Trough serum lamoTRIgine concentrations gradually increased and were approximately 2-fold higher at the end of the week of inactive treatment ("pill-free" week) compared with trough serum lamoTRIgine concentrations at the end of the active hormone cycle. This increase occurred in women not taking a drug that increased the clearance of lamoTRIgine (carBAMazepine, phenytoin, PHENobarbital, primidone, or rifAMPin). Dosage adjustment of lamoTRIgine will be necessary in women taking estrogen-containing oral contraceptives 5.
Common questions
Can I take Lamotrigine and Estradiol together?
Reduced lamoTRIgine exposure and an increased risk of seizures Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lamotrigine and Estradiol interaction?
It is rated moderate. Can be significant — usually manageable with 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 Lamotrigine or 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 (5)
- Product Information: SUBVENITE® oral suspension, lamotrigine oral suspension. OWP Pharmaceuticals, Inc. (per FDA), Lisle, IL, 2025. DailyMed
- Christensen J, Petrenaite V, Atterman J, et al: Oral contraceptives induce lamotrigine metabolism: evidence from a double-blind, placebo-controlled trial. Epilepsia 2007; 48(3):484-489. PubMed
- Sabers A, Buchholt J, Uldall P, et al: Lamotrigine plasma levels reduced by oral contraceptives. Epilepsy Res 2001; 47:151-154. DOI
- Sabers A, Ohman I, Christensen J, et al: Oral contraceptives reduce lamotrigine plasma levels. Neurology 2003; 61(4):1-4. PubMed
- Product Information: LAMICTAL(R) oral tablets, chewable dispersible oral tablets, lamotrigine oral tablets chewable dispersible oral tablets. GlaxoSmithKline, Research Triangle Park, NC, 2006. DailyMed
Keep reading about Lamotrigine
Keep reading about 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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist