Lamotrigine and the Oral Contraceptive Pill – Are Dose Adjustments Needed?

Time to read: 3 minutes

Oral contraceptive pills (OCPs) can interact with the excretion of lamotrigine, requiring dose adjustments. Lamotrigine, however, does not reduce the efficacy of OCPs.

The major route of elimination of lamotrigine is glucuronidation, and Ethinyl estradiol of the combined OC is a well-known inducer of uridine-diphosphate glucuronsyl transferase isoenzymes. These enzymes are a major phase II drug-metabolism enzyme superfamily involved in glucuronidation. Thus, Ethinyl Estradiol increases the excretion of Lamotrigine.
Lamotrigine clearance increases around 2.1-fold.
Combined OCPs also reduce the blood level of lamotrigine by 40–60% if the patient was not already taking enzyme-inducing Anti-epileptic drugs (AEDs). This interaction thus has major implications for seizure and mood stabilisation in women.
When women taking lamotrigine also begin OC use, the level of lamotrigine may decline by 50% and increase seizure risk or a relapse of the mood disorder. To prevent this interaction, lamotrigine levels should be checked before, and after starting OCPs, and dose adjustments should be made based on clinical monitoring for seizure control and lamotrigine levels. [Reddy, 2010]
Progestogen-only pills do not alter lamotrigine serum concentrations.

Lamotrigine – Mechanism of Action, Efficacy, Side Effects and Clinical Pearls

Below are some of the recommendations from the PI.

Starting lamotrigine in patients already taking hormonal contraceptives

No change

Starting hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking enzyme inducers of lamotrigine glucuronidation:

The maintenance dose of lamotrigine will, in most cases, need to be increased by as much as two-fold.

Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking enzyme inducers of lamotrigine glucuronidation:

The maintenance dose of lamotrigine will, in most cases, need to be decreased by as much as 50%

Below is a summary of recommendations by the Faculty of Sexual and Reproductive Health of the Royal College of the Obstetricians and Gynaecologists [FSRH CEU Clinical Guidance: Drug Interactions with Hormonal Contraception Jan 2018]

Update FSRH 2022 Guidance :

There have been some additional changes to the above guidance. Below is a summary: [FSRH, 2022]

Lamotrigine, when used alongside combined hormonal contraception (ethinylestradiol/levonorgestrel), appears to reduce exposure to levonorgestrel, leading to reduced ovarian suppression and breakthrough bleeding. However, ovulation was not observed.
The impact of this interaction on the contraceptive effectiveness of combined hormonal contraception is unknown, and there are no data on the interaction between lamotrigine and progestogen-only contraceptives.
To maintain the effectiveness of lamotrigine, if combined hormonal contraception is necessary, the lamotrigine dose may need to be increased (possibly up to two-fold), and serum levels should be monitored.
Using a continuous combined hormonal contraceptive regimen (without a hormone-free interval) is recommended to avoid fluctuations in lamotrigine levels.
Individuals using lamotrigine who start a progestogen-only contraceptive should watch out for signs of lamotrigine toxicity (dizziness, ataxia, diplopia), and serum lamotrigine levels should be monitored when the progestogen is discontinued.
It’s advised that when starting or stopping hormonal contraception while on lamotrigine, consultation with the individual’s GP or neurologist/psychiatrist is essential for potential dose adjustments.
The effectiveness of combined hormonal contraception, progestogen-only pills, and the etonogestrel implant might be reduced during lamotrigine use, but no study data are available. Therefore, using additional reliable contraception, such as condoms, is suggested as a precaution.
Lamotrigine is not expected to affect the contraceptive effectiveness of depot medroxyprogesterone acetate, levonorgestrel-releasing intrauterine systems, or copper intrauterine devices.