Ethosuximide

Ethosuximide is a succinimide antiseizure medicine reserved for absence seizures and is first-line for childhood absence epilepsy without generalised tonic-clonic seizures. It does not control tonic-clonic or focal seizures, and may worsen them when used alone in mixed epilepsy.

Mechanism. Blocks T-type calcium channels in thalamic neurons, suppressing the 3 Hz spike-and-wave discharges of absence seizures.

Pharmacokinetics. Absorption is nearly complete and it is not protein bound. Half-life is about 30 hours in children and 40 to 60 hours in adults. It is metabolised mainly by cytochrome P450 3A4, and about 20% is excreted unchanged.

First-line use. Typical absence seizures in children, and absence seizures in adults when valproate is unsuitable. Treatment continues until seizure-free for about 2 years, then specialist-led withdrawal.

• Children 3 to under 6 years, oral ethosuximide: 250 mg daily. Age 6 years and over and adults: 500 mg daily. Increase by 250 mg every 4 to 7 days to a usual maintenance of about 20 mg/kg daily (commonly 1000 to 1500 mg daily). Usual maximum 1500 mg daily; some practice allows 2000 mg daily under monitoring.

• Give once daily, or in two doses if nausea occurs. Adjust by response and level.

Alternative use. Add to or replace valproate, or combine with lamotrigine, when absence seizures persist.

Kidney, liver, weight and age.

• Kidney and liver: use caution and reduce the dose in significant impairment, adjusted to levels.

• Weight: dose by mg/kg in children.

• Older adults: start low.

Contraindications. Hypersensitivity to succinimides.

Serious adverse effects. Blood dyscrasias (leucopenia, agranulocytosis, pancytopenia, aplastic anaemia), Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, systemic lupus-like syndrome, psychosis and suicidal ideation.

Common adverse effects. Nausea, vomiting, abdominal pain, anorexia, hiccup, drowsiness, headache, dizziness and mood or behaviour change.

Interactions. Carbamazepine, phenytoin, phenobarbital and primidone lower levels. Valproate can raise or lower levels. Isoniazid and cytochrome P450 3A4 inhibitors raise levels.

Common prescribing errors. Using it alone when tonic-clonic seizures are present. Missing blood count changes. Stopping abruptly.

Special groups.

• Pregnancy: limited data; if effective, usually continued at the lowest dose. Give folic acid 5 mg daily before conception.

• Breastfeeding: milk levels approach maternal levels; watch for sedation and poor feeding.

• Regional: availability varies and may be limited, so valproate is often used when it is not available.

Formulations. Capsules 250 mg. Syrup 250 mg/5 mL. Take with food to limit nausea.

Monitoring.

• Baseline: full blood count and liver function.

• Ongoing: full blood count periodically, and for any fever, sore throat or bruising. Trough level 40 to 100 mg/L. Review seizure control, mood and behaviour.

Stopping. Taper gradually over weeks, because abrupt withdrawal can cause absence status.

Referral and escalation. Refer if absence seizures persist, tonic-clonic seizures appear, or blood count abnormalities develop.