Rufinamide

Rufinamide is a triazole derivative antiseizure medicine used as adjunct therapy for seizures in Lennox-Gastaut syndrome. It needs food for absorption, is cleared by non-cytochrome enzymes, and shortens the QT interval.

Mechanism. Prolongs the inactive state of voltage-gated sodium channels, limiting sustained firing.

Pharmacokinetics. Food increases absorption by about 34 to 44%. Absorption becomes dose-limited over about 1600 mg daily. Protein binding is about 34% and half-life 6 to 10 hours. Carboxylesterases hydrolyse it to an inactive metabolite, and it is a weak inducer of cytochrome P450 3A4.

Specialist use. Adjunct for seizures in Lennox-Gastaut syndrome in children 1 year and over (some labels 4 years and over) and in adults. Treatment is long term.

• Adults and adolescents 17 years and over, oral rufinamide: 400 to 800 mg daily in two divided doses, increased by 400 to 800 mg every 2 days to a maximum of 3200 mg daily.

• Children 1 year and over: 10 mg/kg daily in two doses, increased by about 10 mg/kg every other day to a target of 45 mg/kg daily or 3200 mg daily, whichever is lower.

• With valproate, clearance falls by up to 70%. Use a lower start (for example 200 mg daily under 30 kg) and a lower maximum (for example 600 mg daily under 30 kg).

Kidney, liver, weight and age.

• Kidney: no adjustment. Haemodialysis may remove drug, so consider a supplement after dialysis.

• Liver: caution in mild impairment; not studied in severe impairment.

• Weight: children under 30 kg are dosed by weight.

Contraindications. Familial short QT syndrome and hypersensitivity.

Serious adverse effects. QT shortening, drug reaction with eosinophilia and systemic symptoms (mainly in children in the first 4 weeks), Stevens-Johnson syndrome, leucopenia, status epilepticus and suicidal ideation.

Common adverse effects. Somnolence, vomiting, headache, dizziness, fatigue, nausea and diplopia.

Interactions. Valproate raises rufinamide levels. Carbamazepine, phenytoin, phenobarbital and primidone lower them. Rufinamide lowers hormonal contraceptive efficacy and carbamazepine and lamotrigine levels, and raises phenytoin. Avoid other QT-shortening drugs.

Common prescribing errors. Not adjusting for valproate. Giving without food. Missing a short QT history.

Special groups.

• Pregnancy: limited data; avoid unless benefit outweighs risk, and use non-hormonal contraception. Give folic acid 5 mg daily before conception.

• Breastfeeding: data are lacking; weigh benefit and risk.

• Regional: seldom available outside specialist centres.

Formulations. Tablets 100, 200 and 400 mg. Oral suspension 40 mg/mL. Give with food in two divided doses.

Monitoring.

• Baseline ECG in people with cardiac risk or interacting drugs.

• Ongoing: rash and fever in the first weeks, full blood count, mood, and seizure frequency.

Stopping. Taper gradually, reducing by about 25% every 2 days. Stop at once for hypersensitivity.

Referral and escalation. Start under specialist care. Refer urgently for rash with fever or organ involvement.