Can I use Seasonale (ethinyl estradiol/levonorgestrel) oral contraceptive while taking lamotrigine?

Can You Take Seasonale Birth Control While Taking Lamotrigine?

You can take Seasonale (ethinyl estradiol/levonorgestrel) while on lamotrigine, but this combination requires significant lamotrigine dose adjustments—typically a 50-100% increase—and carries risks of both contraceptive failure and breakthrough seizures or mood destabilization. 1

The Critical Drug Interaction

Combined hormonal contraceptives (CHCs) like Seasonale significantly reduce lamotrigine plasma levels by more than 50%, which can lead to loss of seizure control or mood destabilization. 1, 2 This interaction occurs because ethinyl estradiol induces lamotrigine glucuronidation, dramatically accelerating its metabolism. 3

• The CDC classifies the lamotrigine-CHC interaction as Category 3 (risks generally outweigh benefits), indicating that theoretical or proven risks usually outweigh advantages. 1
• Pharmacokinetic studies demonstrate that when lamotrigine 300 mg/day is co-administered with combined oral contraceptives containing ethinyl estradiol and levonorgestrel, lamotrigine AUC decreases to 48% and Cmax to 61% of baseline values. 3
• The FDA drug label for ethinyl estradiol explicitly warns that "combined hormonal contraceptives have been shown to significantly decrease plasma concentrations of lamotrigine when co-administered, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary." 2

Required Lamotrigine Dose Adjustments

If you proceed with Seasonale, your lamotrigine dose will need to be increased by approximately 50-100% to maintain therapeutic levels. 1

• This dose increase should be implemented when starting the CHC to prevent breakthrough seizures or mood symptoms. 1
• Close monitoring of lamotrigine levels and clinical response is essential during the titration period. 1, 2
• Critical pitfall: When CHCs are discontinued (including during the pill-free week or if you stop Seasonale), lamotrigine levels will rise dramatically, potentially causing toxicity. The lamotrigine dose must be reduced back to baseline when stopping CHCs. 1

Safer Contraceptive Alternatives

Progestin-only methods and intrauterine devices do not interact with lamotrigine and are classified as Category 1 (no restrictions) by the CDC. 4, 1

Recommended non-interacting options include:

• Progestin-only pills (POPs): No drug interactions reported with lamotrigine. 4, 5
• Depot medroxyprogesterone acetate (DMPA/Depo-Provera): Category 1, no interaction. 4, 1
• Etonogestrel or levonorgestrel implants: No significant interactions with lamotrigine. 4, 1, 5
• Copper IUD or levonorgestrel IUD: Category 1, no reported interactions. 1

These methods avoid the complex dosing adjustments and potential for breakthrough seizures or contraceptive failure that occur with CHC-lamotrigine combinations. 1

Bidirectional Interaction Concerns

While lamotrigine levels decrease with CHCs, there is also a modest reduction in levonorgestrel levels (approximately 19% decrease in AUC) when combined with lamotrigine, though ovulation suppression appears maintained. 3

• In pharmacokinetic studies, levonorgestrel AUC decreased to 81% and Cmax to 88% of baseline when co-administered with lamotrigine 300 mg/day. 3
• Despite these reductions, hormonal markers (FSH, LH, progesterone) suggested ovulation remained suppressed, though 32% of subjects experienced intermenstrual bleeding. 3
• This raises theoretical concerns about contraceptive efficacy, particularly with extended-cycle formulations like Seasonale where consistent hormone levels are critical. 3

Clinical Management Algorithm

If you choose to use Seasonale with lamotrigine:

1. Before starting Seasonale: Establish baseline lamotrigine levels and clinical stability. 1
2. When initiating Seasonale: Increase lamotrigine dose by 50-100% over 2-4 weeks, monitoring for efficacy. 1
3. During continuous use: Monitor for breakthrough bleeding (suggests possible contraceptive failure) and seizure/mood symptoms. 1, 3
4. If discontinuing Seasonale: Reduce lamotrigine dose back to baseline over 2-4 weeks to prevent toxicity. 1
5. During pill-free intervals: Be aware that even the 7-day hormone-free interval in standard CHCs can cause lamotrigine level fluctuations; Seasonale's extended cycles may offer more stability but still require careful management during the hormone-free week. 1

Bottom Line Recommendation

Given the significant bidirectional interaction, complex dose adjustments required, and availability of equally effective non-interacting contraceptive options, strongly consider switching to a progestin-only method or IUD rather than using Seasonale with lamotrigine. 1 If Seasonale is preferred for menstrual management reasons, proceed only with close neurologic monitoring and appropriate lamotrigine dose increases. 1, 2