brivaracetam, Briviact, Brivlera

 Indications

Partial-onset seizures (adjunct).

Action

Displays a high and selective affinity for synaptic vesicle

protein 2A (SV2A) in the brain, which may contribute

to its anticonvulsant effect. Therapeutic Effects:

Decreased incidence of seizures.

Pharmacokinetics

Absorption: Rapidly and completely absorbed following

oral administration.

Distribution: Widely distributed to tissues.

Metabolism and Excretion: Hepatic and extrahepatic

amidase-mediated hydrolysis of the amide moiety

to form carboxylic acid metabolite (primary route) and

hydroxylation primarily by CYP2C19 to form the hydroxy

metabolite (secondary route) (all metabolites inactive).

The CYP2C19 enzyme system exhibits genetic

polymorphism; poor metabolizers may have significantlyqbrivaracetam

concentrations and anqrisk of

adverse effects. 95% excreted by the kidneys (10%

excreted unchanged).

Half-life: 9 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

PO unknown 1–4hr† unknown

†1 hr in fasting state; 4 hr with high-fat meal.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; End-stage renal

disease; Lactation: Discontinue brivaracetam or discontinue

breast feeding.

Use Cautiously in: All patients (mayqrisk of suicidal

thoughts/behaviors); Patients who are known

or suspected to be poor CYP2C19 metabolizers (may

require dosep); Hepatic impairment (doseprecommended);

OB: Use only if potential benefit justifies potential

risk to fetus; Pedi: Safety and effectiveness not established

in children 16 yr; Geri:prenal and hepatic

function (dosepmay be necessary).

Adverse Reactions/Side Effects

CNS: SUICIDAL THOUGHTS/BEHAVIOR, aggression, agitation,

anger, apathy, belligerence, anxiety, depression,

dizziness, drowsiness, hallucinations, irritability, mood

swings, paranoia, psychosis, restlessness, tearfulness,

euphoria, fatigue. EENT: nystagmus. GI: constipation,

dysgeusia, nausea, vomiting. Hemat: leukopenia.

Neuro: ataxia, balance disorder, coordination difficulties,

vertigo. Local: infusion site pain. Misc: HYPERSENSITIVITY

(including bronchospasm and angioedema).

Interactions

Drug-Drug: CYP2C19 inducers including rifampin

mayplevels and effectiveness;qdose of brivaracetam

by up to 100%. Concurrent use with carbamazepine

mayqlevels of carbamazepine-epoxide (active metabolite);

considerpdose of carbamazepine if tolerability

issues occur. Mayqlevels of phenytoin.

Route/Dosage

PO, IV (Adults and Children 16 yrs): 50 mg twice

daily; may be titrated down to 25 mg twice daily or up

to 100 mg twice daily based on tolerability and effectiveness.

Hepatic Impairment

PO, IV (Adults and Children 16 yrs): 25 mg twice

daily; titrate based on tolerability and effectiveness

(max dose75 mg twice daily).

Availability

Oral solution (raspberry-flavored): 10 mg/mL.

Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg. Solution

for injection: 10 mg/mL.