What is the interaction between Norgee (triphasic birth control) and Lamictal (lamotrigine)?

Bidirectional Drug Interaction Between Norgee (Triphasic Birth Control) and Lamictal (Lamotrigine)

Combined oral contraceptives containing ethinyl estradiol significantly decrease lamotrigine levels by approximately 50%, which can lead to breakthrough seizures, while lamotrigine does not reduce contraceptive efficacy but this interaction requires either avoiding COCs in favor of alternative contraception or implementing careful dose adjustments with close monitoring. 1

Mechanism and Clinical Impact

The interaction between combined oral contraceptives (COCs) and lamotrigine is primarily unidirectional and clinically significant:

• COCs decrease lamotrigine levels substantially through enhanced glucuronidation, the primary metabolic pathway for lamotrigine. This reduction in lamotrigine concentrations can compromise seizure control. 1

• The U.S. Medical Eligibility Criteria classifies lamotrigine as Category 3 when used with COCs, meaning the risks generally outweigh the benefits. This classification applies specifically to lamotrigine monotherapy used concurrently with COCs. 1

• Seizure breakthrough has been documented in clinical trials when women using both lamotrigine and COCs experienced significant drops in lamotrigine levels. 1

Critical Management Considerations

For Women Currently on Lamotrigine Who Want Contraception:

• Strongly consider non-hormonal or progestin-only alternatives rather than combined hormonal contraceptives. 1

• Depot medroxyprogesterone acetate (DMPA) does not interact with lamotrigine and represents a safer hormonal option. 1

• Intrauterine devices (both copper and levonorgestrel-releasing) are excellent alternatives that avoid this interaction entirely. 1

• Progestin-only pills, implants, and barrier methods should be prioritized over combined hormonal contraceptives. 1

If COCs Must Be Used:

• Lamotrigine dose increases of approximately 50-100% may be necessary when initiating COCs to maintain therapeutic levels. 1

• Close monitoring for seizure activity is essential during the hormone-free interval (placebo week) when lamotrigine levels may fluctuate further. 1

• Extended or continuous cycle regimens that eliminate the hormone-free interval can minimize fluctuations in lamotrigine levels and may be preferable if COCs are chosen. 1

• Use preparations containing at least 30 μg ethinyl estradiol if a COC is selected, though this does not eliminate the interaction. 1

Important Caveats

Anticonvulsant Regimens:

• This interaction applies specifically to lamotrigine monotherapy. When lamotrigine is combined with non-enzyme-inducing antiepileptic drugs (such as sodium valproate), the interaction with COCs may differ. 1

• Enzyme-inducing anticonvulsants (phenytoin, carbamazepine, barbiturates, topiramate, oxcarbazepine) have the opposite effect—they decrease COC efficacy rather than affecting the anticonvulsant levels. 1, 2

Triphasic Formulations:

• Norgee is a triphasic formulation containing varying doses of ethinyl estradiol and norgestimate across the cycle. The interaction mechanism remains the same as with monophasic COCs since all phases contain ethinyl estradiol. 1, 3

• No evidence suggests triphasic formulations interact differently with lamotrigine compared to monophasic preparations—the ethinyl estradiol component drives the interaction regardless of phasic regimen. 3, 4

Contraceptive Efficacy

• Lamotrigine does not reduce the contraceptive effectiveness of COCs, so pregnancy risk from contraceptive failure is not the primary concern. 1

• The main risk is loss of seizure control due to subtherapeutic lamotrigine levels, not contraceptive failure. 1

Recommended Clinical Approach

First-line recommendation: Switch to a non-interacting contraceptive method such as DMPA, IUD (copper or levonorgestrel), progestin-only pill, or etonogestrel implant. 1

If patient insists on COCs: Coordinate care with neurology, increase lamotrigine dose by 50-100%, monitor seizure frequency closely, consider extended-cycle regimens to minimize hormone fluctuations, and use preparations with at least 30 μg ethinyl estradiol. 1

Avoid this combination when possible given the Category 3 classification and documented risk of breakthrough seizures. 1