SV2A Ligands

SV2A ligands bind synaptic vesicle protein 2A, modulating neurotransmitter release. Levetiracetam and brivaracetam have broad spectrum activity, few interactions and no enzyme induction.

Pharmacokinetics. Levetiracetam is renally cleared (66 percent unchanged) with a half life of 6 to 8 hours and negligible protein binding. Brivaracetam is hepatically metabolised.

• Levetiracetam 250 to 500 mg twice daily, increased every 2 weeks to 500 to 1,500 mg twice daily; maximum 3,000 mg daily. Intravenous 1,000 to 3,000 mg over 15 minutes.
• Brivaracetam 25 to 50 mg twice daily, increased to 50 to 100 mg twice daily.

Differences. Brivaracetam has higher affinity and may cause fewer behavioural effects, but experience is less. Neither needs routine levels.

• Focal seizures, generalised tonic-clonic seizures and myoclonic seizures: levetiracetam is first-line, including in women of childbearing potential.
• Acute and perioperative use: intravenous levetiracetam when oral intake is impossible.
• Status epilepticus: second-line, 60 mg/kg intravenously (maximum 4,500 mg) over 10 minutes.
• Drug interactions: preferred where enzyme inducers or antiretrovirals are in use.

Selection. Avoid in people with prominent mood or behavioural disorders if alternatives exist.

Contraindications. Hypersensitivity.

Adverse effects. Somnolence, dizziness, irritability, aggression, depression and psychosis. Rare Stevens-Johnson syndrome and pancytopenia.

Interactions. Few. Rifampicin lowers brivaracetam levels, so its dose may need doubling. Carbamazepine raises an active brivaracetam metabolite.

Special groups.

• Kidney impairment (levetiracetam): creatinine clearance 50 to 80 mL/min, 500 to 1,000 mg twice daily; 30 to 49 mL/min, 250 to 750 mg twice daily; under 30 mL/min, 250 to 500 mg twice daily; haemodialysis, 500 to 1,000 mg once daily plus a 250 to 500 mg supplement after dialysis.
• Liver impairment: brivaracetam maximum 150 mg daily; start 25 mg twice daily.
• Pregnancy: low malformation risk; levels fall, so monitor control.
• Breastfeeding: acceptable; watch for infant sedation.
• Children: levetiracetam 10 to 30 mg/kg twice daily.
• Older adults: start low and adjust to kidney function.

Monitoring. Mood and behaviour, kidney function, seizure control.

Referral and escalation. New depression, psychosis or suicidal thoughts; seizure breakthrough despite adherence.