Brivaracetam

Brivaracetam is a racetam antiseizure medicine used as adjunct therapy for focal seizures. It is a close relative of levetiracetam with higher affinity for its target, a faster brain onset, no need for titration and, in many people, fewer behavioural effects.

Mechanism. Binds synaptic vesicle protein 2A with 15 to 30 times the affinity of levetiracetam, and may also inhibit sodium channels at higher concentrations.

Pharmacokinetics. Bioavailability is near 100% and protein binding under 20%. Half-life is about 9 hours. It is cleared mainly by hydrolysis and by cytochrome P450 2C19 hydroxylation, and over 95% is excreted in urine, mostly as inactive metabolites.

First-line and alternative use. Adjunct for focal seizures with or without secondary generalisation. Treatment is long term.

• Adults and adolescents 50 kg and over, oral or intravenous brivaracetam: start 50 mg twice daily (25 mg twice daily if tolerability is a concern). Usual range 25 to 100 mg twice daily. Maximum 200 mg daily. No loading dose or slow titration is needed. Oral and intravenous doses are equal.

• Children by weight, twice daily: 10 to under 20 kg, 0.5 to 1.5 mg/kg; 20 to under 50 kg, 0.5 to 1.25 mg/kg; 50 kg and over, adult dose.

• Rifampicin or other strong inducers: increase the dose by up to 100%, to a maximum of 400 mg daily, during co-treatment, and reduce again after stopping.

Kidney, liver, weight and age.

• Kidney: no adjustment. Not advised in end-stage disease on dialysis.

• Liver: in all grades of impairment, start 25 mg twice daily with a maximum of 75 mg twice daily.

• Older adults: no adjustment; monitor dizziness and falls.

Contraindications. Hypersensitivity to brivaracetam or other pyrrolidone derivatives.

Serious adverse effects. Suicidal ideation, psychotic reactions, angioedema, neutropenia (rare), and severe skin reactions (rare).

Common adverse effects. Somnolence, dizziness, fatigue, nausea, irritability and depressed mood.

Interactions. Rifampicin lowers levels by about 45%. Carbamazepine, phenytoin and phenobarbital lower levels by 20 to 26%. Brivaracetam raises carbamazepine epoxide and, at 200 mg daily, phenytoin by about 20%. Cytochrome P450 2C19 inhibitors raise levels modestly. Alcohol adds sedation.

Common prescribing errors. Adding it to levetiracetam, which gives no extra benefit. Not raising the dose with rifampicin. Using full doses in liver impairment.

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 for sedation and poor feeding.

• Regional: availability and cost often limit use, and rifampicin co-treatment for tuberculosis needs dose planning.

Formulations. Tablets 10, 25, 50, 75 and 100 mg. Oral solution 10 mg/mL. Intravenous solution 50 mg in 5 mL. Take with or without food.

Preparation. The intravenous solution may be given undiluted as a bolus over 2 minutes or, diluted in 0.9% sodium chloride, 5% glucose or Ringer lactate, as an infusion over 15 minutes.

Monitoring. Mood, behaviour, sedation and falls at each review. Blood count if infection or fever develops. Levels are not routine.

Stopping. Taper by 50 mg daily each week, with a final week at 20 mg daily.

Referral and escalation. Refer for persistent seizures, planned pregnancy, or psychiatric symptoms.