lamotrigine
antiepileptic drug· Brands: LamictalPO
Mechanism of action
Lamotrigine is a phenyltriazine derivative that blocks voltage-dependent sodium channels, stabilizing neuronal membranes and reducing the release of excitatory amino acids, particularly glutamate. This action is thought to underlie its anticonvulsant and mood-stabilizing properties.
Pharmacokinetics
Lamotrigine is rapidly and almost completely absorbed after oral administration, with a bioavailability of approximately 98%. It undergoes metabolism in the liver, primarily via glucuronidation, and it can induce its own metabolism, resulting in a decrease in half-life over time. The elimination half-life is about 25 to 30 hours in patients receiving monotherapy, but it is shortened by enzyme-inducing antiepileptics and prolonged by valproate. Plasma protein binding is approximately 55%. Excretion is predominantly renal, as glucuronide conjugates.
Indications & dosing
Epilepsy: partial seizures (monotherapy or adjunctive)
Titrate slowly starting at 25 mg/day; lower doses with valproate, higher with enzyme inducers.
- adult · PO: 100–200 mg Once daily · Titrate slowly starting at 25 mg/day; lower doses with valproate, higher with enzyme inducers.
Epilepsy: generalized tonic-clonic seizures
Use same titration schedule as for partial seizures.
- adult · PO: 100–200 mg Once daily · Use same titration schedule as for partial seizures.
Lennox-Gastaut syndrome
Weight-based dosing; titrate slowly, reduce dose with valproate.
- pediatric · PO: 1–3 mg/kg/day Once daily · Weight-based dosing; titrate slowly, reduce dose with valproate.
Bipolar disorder: maintenance
Titrate to 200 mg/day standard; may increase to 400 mg/day if needed.
- adult · PO: 200–400 mg Once daily · Titrate to 200 mg/day standard; may increase to 400 mg/day if needed.
Contraindications & precautions
- Known hypersensitivity to lamotrigine or its excipients · Rare, but can cause anaphylaxis.
- History of serious skin rash (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) induced by lamotrigine or other antiepileptic drugs · Re-exposure may be fatal.
- Severe hepatic impairment · Dose adjustment and close monitoring required.
- Initiate treatment with a low dose and titrate slowly to minimise the risk of serious rash.
- Advise patients to seek immediate medical attention if they develop a skin rash, fever, or swelling of the face.
- Administer with caution in hepatic impairment; consider dose reduction.
- Monitor for drug interactions, especially with valproate, carbamazepine, and hormonal contraceptives, which may alter lamotrigine levels.
- Avoid abrupt withdrawal of lamotrigine; taper gradually to prevent rebound seizure activity.
- Caution patients about potential dizziness and ataxia, which may impair driving or operating machinery.
Adverse effects
- Dizziness
- Headache
- Diplopia
- Ataxia
- Nausea
- Vomiting
- Rashserious
- Stevens-Johnson syndrome / toxic epidermal necrolysisserious
- Angioedemaserious
- Aseptic meningitisserious
Interactions
- valproic acidmajorWhen valproic acid and lamotrigine are co-prescribed, the starting dose of lamotrigine should be reduced to approximately half of the standard initiating dose, and the subsequent titration should be slower, with increments every alternate week. The dose of valproic acid may also need adjustment. Prescribers should monitor the patient for signs of rash, fever, or other hypersensitivity reactions, especially during the first few months of therapy. Routine monitoring of lamotrigine serum concentrations can be helpful, though not universally available. If a rash develops, lamotrigine should be discontinued immediately. This combination is best managed by a specialist with expertise in epilepsy.
- carbamazepinemajorMonitor lamotrigine plasma concentrations and clinical response when carbamazepine is initiated, adjusted, or discontinued. Increase the lamotrigine dose when carbamazepine is added, and decrease it when carbamazepine is stopped. Dose adjustments should be based on therapeutic drug monitoring and the patient's clinical status. Follow local prescribing guidelines and specialist advice.
Renal & hepatic adjustment
- eGFR 0–29: Reduce maintenance dose by 50%; use lower initial doses and titrate slowly. Monitor closely for adverse effects.
- eGFR 30–59: No specific dose adjustment required; monitor for adverse effects and consider slower titration.
- Hepatic impairment (mild): No adjustment required; monitor for adverse effects.
- Hepatic impairment (moderate): Reduce initial dose and maintenance dose by 50%; titrate slowly.
- Hepatic impairment (severe): Reduce initial dose and maintenance dose by 75%; titrate slowly and monitor closely.
Monitoring, pregnancy & toxicity
- Skin rash · At start of treatment and during dose titration, especially first 8 weeks
- Neurological status (dizziness, ataxia, diplopia) · Regularly during dose titration and maintenance
- Mood and behavioural changes · Regularly, especially in children and bipolar disorder
- Serum lamotrigine concentration · If toxicity suspected, non-response, or interacting drugs
- Signs of hypersensitivity (fever, lymphadenopathy, facial oedema) · Early treatment
- Pregnancy: Lamotrigine is a second-line option during pregnancy. It should not be discontinued abruptly. If used, dose adjustment may be needed due to increased clearance. Discuss risks and benefits. There is an increased risk of oral clefts with first-trimester exposure. Use with caution and consider monitoring serum levels and maternal condition.
- Toxicity: Cerebellar signs (ataxia, nystagmus, dizziness) · Supportive care, close observation
- Toxicity: Seizures · Administer benzodiazepines (e.g. lorazepam) and supportive care
- Toxicity: Cardiac conduction abnormalities (PR prolongation, QRS widening) · ECG monitoring and supportive care; consider intravenous sodium bicarbonate if significant QRS widening
Clinical notes
Slow titration is essential to reduce the risk of serious skin reactions, including Stevens-Johnson syndrome. The starting dose and titration schedule vary according to whether the patient is taking valproate, enzyme-inducing antiepileptics, or neither. Lamotrigine is also licensed for the maintenance treatment of bipolar disorder, particularly for preventing depressive episodes. It has a favourable metabolic profile, with little effect on weight, but it can interact with oral contraceptives, which may lower lamotrigine levels. If a rash develops, the drug should be stopped immediately.
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BNF; local formulary