Section 01 · Monograph

Lamotrigine

Reviewed Nov 2026FDA label

LamictalNa+ channel blocker

Forms: Tab: 25, 100, 150, 200mg | Chew: 2, 5, 25mg | XR: 25-300mg | ODT: 25-200mg
Dose: 200-400mg/day
MOA: Blocks voltage-gated Na+ channels

Black Box Warning

Serious, sometimes life-threatening rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have occurred — the rate of serious rash is higher in pediatric patients than in adults
Risk is increased by coadministration with valproate, exceeding the recommended initial dose, or exceeding the recommended rate of dose escalation
Lamotrigine should be discontinued at the first sign of rash, unless the rash is clearly not drug-related

Adjunctive therapy for partial-onset seizures, age 2+FDA-labeled
Adjunctive therapy for primary generalized tonic-clonic seizures, age 2+FDA-labeled
Adjunctive therapy for generalized seizures of Lennox-Gastaut syndrome, age 2+FDA-labeled
Conversion to monotherapy in adults with partial-onset seizures currently on a single enzyme-inducing AED or on valproateFDA-labeled
Maintenance treatment of bipolar I disorder to delay time to occurrence of mood episodesFDA-labeled

Blocks voltage-gated Na+ channels, stabilizing neuronal membranes and inhibiting release of excitatory neurotransmitters, particularly glutamate
Weak inhibitory activity at 5-HT3 receptors

Slow titration is mandatory to reduce rash risk — do not exceed recommended starting doses or escalation rate
Adults not on valproate or enzyme-inducing AEDs: 25mg/day for 2 weeks, then 50mg/day for 2 weeks, then increase by 50–100mg/day every 1–2 weeks to usual maintenance of 225–375mg/day in divided doses
Adults on valproate (with or without other AEDs): much slower/lower titration — 25mg every other day for 2 weeks, then 25mg/day for 2 weeks, then increase by 25–50mg every 1–2 weeks to usual maintenance of 100–200mg/day
Adults on enzyme-inducing AEDs without valproate: 50mg/day for 2 weeks, then 100mg/day in divided doses for 2 weeks, then increase by 100mg/day weekly to usual maintenance of 300–500mg/day in divided doses
If lamotrigine is discontinued for an extended period (roughly more than 5 half-lives), restart at the initial titration schedule rather than resuming the prior maintenance dose
Extended-release (XR) formulation is dosed once daily using a separate titration schedule

Valproate inhibits glucuronidation of lamotrigine, increasing lamotrigine concentrations roughly 2-fold — requires a slower titration and lower maintenance dose
Enzyme-inducing AEDs (carbamazepine, phenytoin, phenobarbital, primidone) and rifampin increase lamotrigine clearance and lower levels — requires faster titration and higher maintenance dose
Estrogen-containing oral contraceptives decrease lamotrigine concentrations by roughly 50% — dose may need to be increased when starting, and decreased when stopping, hormonal contraception
Concomitant carbamazepine increases CNS adverse effects (dizziness, diplopia, ataxia) even without a significant pharmacokinetic interaction

Common: dizziness, headache, diplopia, ataxia, nausea, somnolence, rash
Serious rash including Stevens-Johnson syndrome/TEN — see boxed warning
Hemophagocytic lymphohistiocytosis (HLH) — rare but life-threatening immune reaction reported
Aseptic meningitis
Blood dyscrasias
Suicidal ideation/behavior — monitor for new or worsening depression or mood changes

Skin for rash, especially during initial titration
Mood and behavioral changes
Clinical response with dose changes of interacting drugs (valproate, enzyme inducers, hormonal contraceptives)

Lamotrigine clearance can increase substantially during pregnancy, particularly in the second and third trimesters, sometimes requiring dose increases with a corresponding reduction postpartum
Consider enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry
Excreted into breast milk with clinically relevant infant serum levels reported — monitor breastfed infants