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

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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 in 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.

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]

References