Lamotrigine

Adjunctive epilepsy treatment at age ≥2: partial-onset, primary generalized tonic-clonic and Lennox-Gastaut generalized seizures. Conversion to monotherapy at age ≥16 with partial-onset seizures applies when receiving a single carbamazepine, phenytoin, phenobarbital, primidone or valproate regimen. Adult bipolar I maintenance delays mood episodes after standard acute treatment; acute mood-episode efficacy is not established.

XR: adjunctive PGTC or partial-onset seizures, with/without secondary generalization, at age ≥13. Conversion to monotherapy at age ≥13 applies to partial-onset seizures on a single AED. Initial monotherapy or simultaneous conversion from multiple AEDs is not established. XR has no labeled bipolar-maintenance indication.

Co-treatment groups refer to carbamazepine, phenytoin, phenobarbital or primidone as the listed inducing AEDs. Rifampin/lopinavir-ritonavir follow inducer guidance; estrogen-containing products and atazanavir-ritonavir require the separate label instructions. All numbers are total daily dose unless noted. These tables are label schedules for the stated indication, not a self-directed titration plan.

Use whole 2/5/25 mg dispersible tablets; round calculated starting doses and increments down to whole tablets. For low weights on valproate, follow the label’s Table 3 weight guide rather than a partial tablet/liquid quantity. Under 30 kg, maintenance may need up to 50% increase by response; label maxima and specialist plan still apply.

The 400 mg target applies to the specified inducer regimen, not routine monotherapy: trials showed no additional monotherapy benefit above 200 mg/day. Reassess ongoing maintenance, especially beyond 16 weeks.

XR is once daily; week 8 or later increases must not exceed 100 mg/day at weekly intervals. Swallow whole without crushing, chewing or dividing.

IR conversion-to-monotherapy maintenance is 500 mg/day in 2 doses; XR monotherapy maintenance is 250–300 mg once daily. Follow each label’s exact stepwise AED-withdrawal regimen; the adjunctive table alone is insufficient for conversion. IR→XR may begin at the same total daily dose, with close seizure monitoring, especially with enzyme inducers. After >5 half-lives off treatment, restart initial titration; half-life varies with other drugs, so there is no universal missed-day cutoff. Do not restart after a drug-related rash unless benefits clearly outweigh risks. Taper over ≥2 weeks, about 50% weekly, unless safety requires faster withdrawal.

IR can be taken with or without food. Dispersible tablets may be swallowed, chewed with a little liquid or dispersed in enough water/diluted juice to cover them; consume the entire mixture promptly, never a partial quantity. ODT dissolves on the tongue and is swallowed with/without water. Mild hepatic impairment: no adjustment; moderate/severe without ascites: generally reduce starting, escalation and maintenance doses about 25%; severe with ascites: about 50%. Significant renal impairment may need lower maintenance doses; use caution in severe impairment.

Known lamotrigine or ingredient hypersensitivity, including previous hypersensitivity rash, angioedema, urticaria, extensive itching or mucosal ulceration.

Stevens-Johnson syndrome, toxic epidermal necrolysis and rash-related death can occur. Risk is higher in children, with valproate, excessive starting/escalation doses, and HLA-B*1502. Most life-threatening rashes occur at 2–8 weeks, but later reactions occur. Ordinarily discontinue at the first rash unless clearly unrelated. HLA testing cannot replace vigilance; negative status does not eliminate risk.

Dizziness, ataxia, diplopia/blurred vision, headache, nausea, vomiting, somnolence and rash are prominent in epilepsy trials; patterns depend on regimen and population. Serious immune, blood, organ and cardiac events require urgent review. Overdose can cause seizures, coma, ataxia and conduction delay and has been fatal. Hospital/poison-center assessment and supportive care are needed; no specific antidote is known.

• Valproate more than doubles lamotrigine concentrations: lower, slower schedules are required. Carbamazepine, phenytoin, phenobarbital and primidone increase clearance; rifampin and selected protease inhibitors also lower exposure.
• Estrogen-containing oral contraceptives can halve concentrations and levels can approximately double during the pill-free week. Starting/stopping requires a prescribed maintenance adjustment; do not adjust only during the pill-free week.
• Without other glucuronidation inducers, estrogen-pill use may require up to a twofold maintenance increase. When starting pills, increases generally no faster than 50–100 mg/day weekly; when stopping, decrease up to 50%, generally no more than 25% of the total daily dose weekly over 2 weeks, unless response/levels justify otherwise. Initial titration is not altered solely for contraceptive use.
• Other estrogen therapies need clinical monitoring; progestogen-only pills generally do not require this adjustment. Report breakthrough bleeding because reduced contraceptive efficacy cannot be excluded.
• Other cardiac sodium-channel blockers may increase arrhythmia risk. Coadministration with narrow-therapeutic-index OCT2 substrates such as dofetilide is not recommended.

Pregnancy registries have not detected an overall increase or consistent malformation pattern; limitations and animal developmental toxicity remain. Encourage NAAED registry enrollment. Concentrations may fall during pregnancy and return after delivery, requiring clinical/level assessment and dose review. Lamotrigine enters milk; postpartum maternal increases can raise infant exposure. Monitor infant rash, apnea, sedation, poor sucking/weight gain; check infant levels if toxicity is suspected and stop human-milk feeding if toxicity occurs.

IR adjunctive epilepsy begins at age 2; IR conversion is ≥16 and bipolar maintenance is adult. XR epilepsy indications begin at ≥13. Pediatric bipolar efficacy is not established. Older adults need cautious dose selection. Hepatic reductions apply to the full starting, escalation and maintenance schedule; renal impairment may lower maintenance requirements, with limited severe-impairment experience.

The exact anticonvulsant mechanism is unknown; inhibition of voltage-sensitive sodium channels and reduced excitatory transmitter release are proposed. Bipolar therapeutic mechanism is not established. IR oral bioavailability is about 98%, unaffected by food; protein binding about 55%. Predominantly forms an inactive glucuronide, recovered mainly in urine. XR delays absorption and smooths exposure; release forms require the supervised conversion plan.

IR multiple-dose half-life examples

Healthy volunteers without other medicines: 25.4 hours; with valproate: 70.3 hours; epilepsy with listed inducing AEDs: 12.6 hours.

Clinical meaning

Interaction-dependent half-life governs restart assessment.

Plasma monitoring

Consider during interaction/dose changes; dose to clinical response.

• Assess rash/mucosal lesions, fever, lymphadenopathy, blood/organ or meningitis symptoms; investigate urgently when present.
• Monitor seizure control, depression/suicidality, dizziness/ataxia and cardiac symptoms. Assess cardiac history and interacting drugs; no universal ECG schedule is supplied here.
• Review adherence, interruptions, hormone/AED changes and pregnancy/postpartum concentrations/response. Plasma levels may help during changes, without a universally established therapeutic range.
• Confirm positive rapid urine PCP screens with a specific test; lamotrigine can cause false positives.

Follow the written titration exactly; contact the prescriber after interruptions and before restarting. Report rash, mouth sores, fever or swollen nodes immediately. Seek urgent help for palpitations/fainting, severe headache/stiff neck or self-harm thoughts. Avoid driving until effects are known. Verify tablet appearance and IR/XR/ODT/dispersible form, and disclose pregnancy, breastfeeding and hormonal contraception changes.

Appearance / imprint

White, scored, shield-shaped; LAMICTAL / 25.

Manufacturer

GlaxoSmithKline.

Example NDC

0173-0633-02 · bottle of 100.

U.S. status

Prescription.

IR compressed tablets

25, 100, 150 and 200 mg.

Chewable/dispersible tablets for oral suspension

2, 5 and 25 mg.

ODT

25, 50, 100 and 200 mg.

XR tablets

25, 50, 100, 200, 250 and 300 mg.

Titration kits

Different kits for valproate, no listed inducer/valproate, or listed inducer without valproate; choose with prescriber.

IR/dispersible and XR: 25°C, excursions 15–30°C; IR/dispersible dry storage, with light protection as specified for the exact IR package. ODT: 20–25°C, excursions 15–30°C. Do not use torn, broken or missing blisters. XR must remain intact; do not split dispersed mixtures for dosing.