Section 01 · Monograph

Perampanel

Reviewed Nov 2026FDA label

FycompaAMPA antagonist

Black Box Warning

Serious or life-threatening psychiatric and behavioral adverse reactions have been reported, including aggression, hostility, irritability, anger, and homicidal ideation/threats
Symptoms may occur at any time during treatment but are more frequent and severe with higher doses and typically emerge early in the course of treatment
Closely monitor patients, particularly during titration and at higher doses; advise patients and caregivers to contact a healthcare provider immediately if such symptoms develop; dose reduction or discontinuation may be required

Treatment of partial-onset seizures, with or without secondarily generalized seizures, age 4 years and olderFDA-labeled
Adjunctive therapy for primary generalized tonic-clonic seizures, age 12 years and olderFDA-labeled

First-in-class, selective, non-competitive AMPA-type glutamate receptor antagonist on postsynaptic neurons, reducing glutamate-mediated neuronal excitation implicated in seizure generation and spread

Initiate 2mg once daily at bedtime
Titrate by 2mg/day increments no more frequently than weekly, based on response and tolerability
Usual maintenance dose: 8-12mg/day (partial-onset seizures) or 8mg/day (primary generalized tonic-clonic seizures)
Once-daily bedtime dosing supported by a long elimination half-life (approximately 105 hours)
With concomitant strong CYP3A4-inducing AEDs (carbamazepine, phenytoin, oxcarbazepine): consider initiating at 4mg/day with slower/higher titration as tolerated, since inducers substantially lower perampanel levels
Elderly patients: titrate more gradually (e.g., no more than every 2 weeks) given reduced clearance and higher sensitivity to CNS effects

Renal impairment: mild — no adjustment; moderate — use with caution; severe/dialysis — not recommended (not studied)

Hepatic impairment: mild — max 6mg/day; moderate — max 4mg/day; severe — not recommended

Strong CYP3A4 inducers (carbamazepine, phenytoin, oxcarbazepine) reduce perampanel plasma concentrations by roughly 40-67%, often requiring higher perampanel doses
Perampanel is a weak enzyme inducer itself: at 12mg/day it can reduce the effectiveness of levonorgestrel-containing hormonal contraceptives — advise an alternative or additional non-hormonal contraceptive method
Additive CNS depression with alcohol and other CNS depressants — avoid or use extreme caution, particularly during initial titration

Very common: dizziness, somnolence, fatigue
Common: irritability, falls, ataxia, nausea, vertigo, weight gain, balance disorder
Serious psychiatric/behavioral reactions per boxed warning — aggression, hostility, irritability, anger, homicidal ideation
Increased fall risk related to dizziness, ataxia, and gait disturbance
Suicidal ideation/behavior (class effect)
Drug reaction with eosinophilia and systemic symptoms (DRESS) reported rarely

Close monitoring for new or worsening psychiatric/behavioral symptoms (aggression, hostility, irritability, homicidal ideation), especially during titration and at higher doses
Fall risk and neurologic status (dizziness, ataxia, somnolence)
Weight
Hepatic/renal function for dose adjustment
Contraceptive efficacy counseling if on hormonal contraception and receiving doses ≥12mg/day

Animal studies demonstrated developmental toxicity; human data are limited
Encourage enrollment in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334)
Present in animal milk; human lactation data are limited — weigh clinical benefit of treatment against potential infant exposure