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Lamotrigine in Pregnancy — RACP Adult Medicine MCQ

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ModerateClinical PharmacologyLamotrigine in PregnancyRACP Adult Medicine

A 35-year-old woman with epilepsy becomes pregnant on lamotrigine monotherapy. She has been seizure-free for 3 years. Her lamotrigine level is therapeutic at 8 mg/L pre-pregnancy. During the second trimester, she has a breakthrough seizure. Her lamotrigine level is now 3.5 mg/L. What is the explanation?

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Correct answer: A — Increased renal clearance of lamotrigine in pregnancy

Lamotrigine clearance increases dramatically during pregnancy (by up to 300% by the third trimester) due to increased glucuronidation mediated by rising oestrogen levels. This leads to falling drug levels and breakthrough seizures. Lamotrigine levels should be monitored monthly during pregnancy and the dose increased to maintain pre-pregnancy therapeutic levels. After delivery, the dose must be reduced rapidly (within 2–3 weeks) to avoid toxicity as clearance returns to pre-pregnancy rates.

Reference: AMH – 2025 – Antiepileptics in Pregnancy; eTG – 2025 – Neurology