Vigabatrin

Vigabatrin is an irreversible inhibitor of GABA transaminase, used as first-line treatment for infantile spasms, especially with tuberous sclerosis, and as a later-line drug for refractory focal epilepsy. Its major hazard is permanent bilateral concentric visual field constriction, a boxed-warning-level risk.

Mechanism. Irreversibly inhibits GABA transaminase, raising brain GABA. The effect lasts days beyond plasma clearance.

Pharmacokinetics. Oral absorption is good and protein binding is negligible. About 95% is excreted unchanged in urine. Plasma half-life is 5 to 8 hours, but the pharmacodynamic effect lasts much longer.

First-line use. Infantile spasms (West syndrome), with tuberous sclerosis as the strongest indication.

• Infants, oral vigabatrin: 50 mg/kg daily in two doses, increased over 3 days by 25 to 50 mg/kg daily to a maximum of 150 mg/kg daily. If there is no clear response within 2 to 4 weeks, taper and stop. In responders, give the shortest effective course, often about 6 months.

Specialist use. Refractory focal seizures in older children and adults:

• Adults: 1000 mg daily in one or two doses, increased by 500 mg weekly to a usual 2000 to 3000 mg daily. Maximum 3000 mg daily.

• Children by weight: 10 to 15 kg, 500 to 1000 mg daily; 15 to 30 kg, 1000 to 1500 mg daily; 30 to 50 kg, 1500 to 3000 mg daily; over 50 kg, 2000 to 3000 mg daily.

Alternative. Hormonal therapy (prednisolone or corticotropin) is the main alternative first-line therapy for infantile spasms, with doses set by specialists.

Kidney, liver, weight and age.

• Kidney: reduce the dose by 25% for creatinine clearance over 50 to 80 mL/min, 50% for over 30 to 50 mL/min, and 75% for over 10 to 30 mL/min.

• Liver: no adjustment.

• Infants and children: dosed by weight.

Contraindications. Hypersensitivity, and an existing visual field defect unless benefit clearly outweighs risk.

Serious adverse effects. Permanent visual field constriction (up to a third of long-term users), optic neuritis or atrophy, depression, psychosis, suicidal ideation, worsening of myoclonic and absence seizures, peripheral neuropathy, anaemia, and MRI signal change in infants.

Common adverse effects. Somnolence, fatigue, dizziness, irritability, behavioural change, weight gain, tremor and oedema.

Interactions. Phenytoin levels fall by about 20%. Avoid other drugs that damage the retina or optic nerve, such as ethambutol and hydroxychloroquine, which is relevant to tuberculosis treatment.

Common prescribing errors. Continuing without response review. Missing visual monitoring. Using it for generalised epilepsies with myoclonic or absence seizures.

Special groups.

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

• Breastfeeding: excreted into milk; monitor the infant.

• Regional: availability is limited in many settings, and visual field testing is often hard in infants and in low-resource clinics.

Formulations. Tablets 500 mg. Powder sachets 500 mg, dissolved in water. Oral solution 100 mg/mL in some markets. Take with or without food.

Monitoring.

• Visual fields, where cooperation allows, at baseline, every 3 to 6 months during treatment and for 3 to 6 months after stopping. In infants, use electroretinography or specialist assessment. Tell patients and carers to report visual symptoms.

• Review mood, behaviour, weight and seizure frequency. Levels are not used.

Stopping. Taper over 2 to 4 weeks, unless there is visual loss or no response.

Referral and escalation. Refer to a specialist before starting for infantile spasms. Refer urgently to ophthalmology for any visual field loss.