Generic Name

Lamictal

Mechanism

• Selective blockade of voltage‑gated sodium channels → stabilizes hyperexcitable neuronal membranes and reduces repetitive firing.
• Inhibition of glutamate release → ↓ excitatory neurotransmission, which contributes to antidepressant and mood‑stabilizing effects.
• No significant activity at GABA, NMDA, or serotonergic receptors, differentiating it from many other anticonvulsants.

Pharmacokinetics

• Absorption: Rapid oral absorption (t_max ≈ 1 h), high oral bioavailability (~98 %); food does not markedly affect absorption.
• Distribution: Vd ≈ 0.4 L/kg; highly protein‑bound (~90 %) with plasma protein binding largely involving albumin.
• Metabolism: Predominantly glucuronidation via UGT 1A4; minimal CYP450 involvement.
• Elimination: Primarily renal (≈ 80 % excreted unchanged; 20 % as glucuronides); half‑life ~7–13 h (therapeutic steady state ~12 days).
• Special populations: Reduced clearance in pregnancy (due to increased UGT1A4 activity); dose adjustment may be required.

Indications

• Epilepsy
• Primary or adjunctive therapy for partial‑onset seizures.
• Maintenance therapy for generalized tonic‑clonic, absence, myoclonic, and Lennox‑Gastaut syndrome.
• Bipolar Disorder
• Maintenance (add‑on or monotherapy) for bipolar I and II depression and mania to prevent recurrence.
• Off‑label: Some use as adjunctive pain control in neuropathic pain or migraine prophylaxis.

Contraindications

• Contraindication: Prior severe hypersensitivity reaction or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with any anticonvulsant.
• Warnings
• First‑dose reaction (FDR) syndrome: rash with fever, chills, or lymphadenopathy; dose‑wise titration mandatory.
• Pregnancy categories: Pregnancy Category C – risk of fetal malformations (skin rash, SJS/TEN).
• Interacts with hormonal contraceptives (increased metabolism → reduced efficacy).
• Not recommended in patients with severe hepatic impairment or uncontrolled renal disease.

Dosing

• Administration: Oral, with or without food.
• Omission: If a dose is missed, wait at least 24 h before rescue dose; avoid double dosing.
• Long‑term: Maintain at the lowest effective dose; consider gradual tapering over >4 weeks for discontinued use.

Adverse Effects

• Common
• Rash (maculopapular, pruritic) – ~5‑10 % (most during titration).
• Headache, dizziness, blurred vision, nausea, insomnia.
• Mild cognitive disturbances or mood changes.
• Serious
• Stevens–Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) – rare (<0.003 %).
• Myelosuppression (rare).
• Hyponatremia (rare, especially in the elderly).
• Liver enzyme elevations (monitor ALT/AST).

Monitoring

• Baseline & Follow‑up
• CBC, CMP (especially liver enzymes) every 4 weeks for 3 months, then every 3 months.
• Electrolytes & urinalysis if renal disease suspected.
• Pregnancy tests (female of childbearing potential) and contraceptive counseling.
• Drug interactions
• Check for co‑administration with enzyme inducers (e.g., carbamazepine) or inhibitors (e.g., valproate).
• Monitor for reduced efficacy of hormonal contraceptives.

Clinical Pearls

• Start low, titrate slow: A *15‑day* titration schedule maximizes safety, especially in patients with a history of rash or using enzyme‑inducing anticonvulsants.
• Watch for atypical rashes: A rash that spreads rapidly or occurs with fever is a red flag for SJS/TEN; discontinue immediately and seek dermatology.
• Pregnancy & lactation: Cross the placenta; consider the risk–benefit ratio—lamotrigine is not recommended during pregnancy unless the benefit outweighs the risk of fetal skin disease.
• Mood stabilizer vs anticonvulsant: The mechanism (glutamate suppression) underpins its efficacy in bipolar depression, where traditional anticonvulsants may be less helpful.
• Concomitant hormonal contraception: Enzyme induction can lower levonorgestrel/ethinyl estradiol levels; advise use of barrier methods and monitor ovulation.
• Dose adjustment in renal insufficiency: Though mainly metabolized hepatically, severe renal dysfunction can delay clearance; consider dose reduction or extended dosing interval.

*This drug card provides succinct, high‑yield information for clinicians and trainees; use it as a quick reference while ensuring patient‑specific adjustments and monitoring.*