Tiagabine

Tiagabine is a GABA reuptake inhibitor used as adjunct treatment for focal seizures in adults and adolescents. It is rarely used now because of its tolerability and its risk of seizures and non-convulsive status in people without epilepsy.

Mechanism. Blocks the GAT-1 transporter, which raises synaptic GABA.

Pharmacokinetics. Bioavailability about 90%, protein binding about 96%, and half-life 7 to 9 hours (2 to 3 hours with enzyme inducers). Metabolised by cytochrome P450 3A4. Food slows absorption and reduces peak effects.

Alternative use. Adjunct for refractory focal seizures when other drugs have failed. Treatment is long term and reviewed at each visit.

• Adults and adolescents 12 years and over, oral tiagabine: start 4 mg once daily for 1 week, then increase by 4 to 8 mg each week. Give in 2 to 4 divided doses. Some labels start at 5 to 10 mg daily.

• Usual maintenance with enzyme inducers: 30 to 56 mg daily. Without inducers: about 15 to 30 mg daily. Usual maximum 56 mg daily.

• Adolescents 12 to 18 years: start 4 mg daily, increase by 4 mg weekly for 2 weeks and then by 4 to 8 mg weekly, to a maximum of 32 mg daily.

Kidney, liver, weight and age.

• Kidney: no adjustment.

• Liver: reduce dose and extend the interval in moderate impairment; avoid in severe impairment.

• Older adults: start low and titrate slowly.

Contraindications. Severe hepatic impairment and hypersensitivity.

Serious adverse effects. Seizures and non-convulsive status epilepticus (spike-wave stupor), including in people treated off-label for anxiety or pain without epilepsy. Suicidal ideation, severe rash, weakness and visual field effects have been reported.

Common adverse effects. Dizziness, tiredness, nervousness, tremor, poor concentration, depressed mood and abdominal pain.

Interactions. Carbamazepine, phenytoin and phenobarbital lower levels. Valproate raises free tiagabine by displacement. Tiagabine lowers valproate levels slightly.

Common prescribing errors. Using the same dose with and without enzyme inducers. Off-label use in people without epilepsy. Giving on an empty stomach.

Special groups.

• Pregnancy: limited data; avoid unless benefit clearly outweighs risk. Give folic acid 5 mg daily before conception.

• Breastfeeding: small amounts enter milk; monitor the infant.

• Regional: seldom stocked, so supply should be confirmed before starting.

Formulations. Tablets in strengths of about 2 to 16 mg, depending on market. Take with food.

Monitoring. Seizure frequency, dizziness, mood and cognition at each review. Levels are not routine.

Stopping. Taper over 2 to 3 weeks, reducing by 4 to 8 mg weekly.

Referral and escalation. Refer if seizures worsen, confusion or stupor develops, or other options have not been tried.