Lacosamide

Lacosamide is a functionalised amino acid antiseizure medicine used for focal seizures, with oral and intravenous forms and a favourable interaction profile. Its main safety concern is PR interval prolongation and conduction block.

Mechanism. Enhances slow inactivation of voltage-gated sodium channels, selectively reducing sustained neuronal firing.

Pharmacokinetics. Bioavailability is near 100%. Protein binding is under 15%. Half-life is about 13 hours. About 40% is excreted unchanged in urine, and the rest is metabolised mainly by cytochrome P450 2C19 to an inactive metabolite.

First-line use. Focal seizures in adults and children, as monotherapy or adjunct. Treatment is long term.

• Adults and adolescents 16 years and over, oral or intravenous lacosamide: start 50 mg twice daily, increase to 100 mg twice daily after 1 week, then by 50 mg twice daily each week. Usual maintenance 100 to 200 mg twice daily. Maximum 400 mg daily as adjunct and 600 mg daily as monotherapy.

• Loading dose: a single 200 mg dose may be given when rapid effect is needed, followed by 100 mg twice daily 12 hours later.

• Children 2 years and over, under 50 kg: start 1 mg/kg twice daily, increase weekly by 1 mg/kg twice daily. Maximum 12 mg/kg daily under 30 kg, and 8 mg/kg daily for 30 to under 50 kg. Children 50 kg and over use adult doses.

Specialist and emergency use. Intravenous lacosamide 200 to 400 mg over 15 to 30 minutes is used off-label as a later-line drug in status epilepticus, with limited evidence.

Kidney, liver, weight and age.

• Kidney: with creatinine clearance of 30 mL/min or under, or end-stage disease, reduce the maximum daily dose by 25% (about 300 mg daily). Give a supplement of up to 50% of the dose after a 4-hour haemodialysis session.

• Liver: mild to moderate impairment, reduce the maximum daily dose by 25%. Not advised in severe impairment.

• Older adults: slow titration and attention to conduction disease.

Contraindications. Second or third degree atrioventricular block and hypersensitivity.

Serious adverse effects. PR interval prolongation, atrioventricular block, syncope, atrial fibrillation or flutter, drug reaction with eosinophilia and systemic symptoms, suicidal ideation, and rare hepatic or blood effects.

Common adverse effects. Dizziness, headache, diplopia, nausea, ataxia and tiredness, more frequent with sodium channel blockers added.

Interactions. Additive PR prolongation with carbamazepine, lamotrigine, pregabalin, beta blockers, verapamil, diltiazem, flecainide and amiodarone. Enzyme inducers modestly lower levels. No meaningful effect on contraceptives or antiretrovirals.

Common prescribing errors. Missing an ECG in people with conduction disease. Not reducing the dose in kidney impairment. Adding it to several sodium channel blockers at full doses.

Special groups.

• Pregnancy: limited data; use only if benefit outweighs risk, and give folic acid 5 mg daily before conception.

• Breastfeeding: excreted into milk; manufacturers advise against use, so weigh the benefit and monitor the infant.

• Regional: a newer drug, often costly or unavailable in low-resource settings.

Formulations. Tablets 50, 100, 150 and 200 mg. Syrup 10 mg/mL. Intravenous solution 10 mg/mL. Take with or without food.

Preparation. The intravenous solution can be given undiluted or diluted in 0.9% sodium chloride, 5% glucose or Ringer lactate, over 15 to 60 minutes.

Monitoring.

• Baseline ECG in people with conduction disease, structural heart disease or interacting drugs. Repeat when the dose reaches a steady maintenance level.

• Review dizziness, falls and mood. Levels are not routine; a guide range is about 10 to 20 mg/L.

Stopping. Taper over at least 1 week, reducing by 200 mg daily each week.

Referral and escalation. Refer for persistent seizures, syncope, bradycardia or conduction abnormality on ECG, or when pregnancy is planned.