PERAMPANEL

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Non-competitive AMPA receptor antagonist; selectively inhibits excitatory neurotransmission by binding to the AMPA subtype of glutamate receptors on postsynaptic neurons.

What the body does with it

Metabolism	Hepatic, primarily via CYP3A4 and CYP3A5, with minor contribution from CYP2C8 and CYP2C9; also undergoes N-acetylation and other Phase II pathways.
Excretion	Primarily hepatic metabolism via CYP3A4/3A5; ~70% excreted in feces (as metabolites, minimal unchanged drug) and ~30% in urine (<2% unchanged perampanel). Biliary excretion contributes to fecal elimination.
Half-life	Terminal elimination half-life is approximately 105 hours (range 70–130 hours) in healthy adults, allowing once-daily dosing. Half-life may be prolonged in hepatic impairment or with CYP3A4 inhibitors.
Protein binding	95–96% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Volume of distribution is approximately 1.1 L/kg (range 0.7–1.7 L/kg), indicating extensive tissue distribution (total body water distribution).
Bioavailability	Absolute oral bioavailability is nearly 100% after oral administration; minimally affected by food (no significant change in AUC).
Onset of Action	Oral: Clinical effect (seizure reduction) typically observed within 1–2 weeks of starting therapy, corresponding to steady-state achieved in approximately 3–4 weeks due to long half-life. No parenteral formulation available.
Duration of Action	Once-daily dosing provides continuous antiepileptic coverage due to long half-life; effects persist for several days after discontinuation due to slow elimination. Duration of action is 24 hours (dosing interval).

Classification & Brands

Dosing & administration

4 mg orally once daily at bedtime; may increase based on response and tolerability by 2 mg every 2 weeks up to 8 mg/day. Maximum dose 12 mg/day.

Dosage form	TABLET
Renal impairment	No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) or on hemodialysis due to lack of data.
Liver impairment	Child-Pugh A: no dose adjustment. Child-Pugh B: 2 mg once daily at bedtime; may increase to 4 mg once daily based on response and tolerability. Child-Pugh C: not recommended.
Pediatric use	Approved for partial-onset seizures in patients aged ≥4 years: 2 mg once daily at bedtime; titrate by 2 mg every 2 weeks based on response and tolerability. Maximum dose 8 mg/day for weight <30 kg, 12 mg/day for weight ≥30 kg.
Geriatric use	Initiate at 2 mg once daily due to potential for decreased clearance; titrate cautiously. Monitor for dizziness, somnolence, and falls. No specific dose adjustment required for age alone, but renal function should be assessed.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong CYP3A4 inducers may decrease efficacy Can cause serious neuropsychiatric events including aggression and hostility.

Breastfeeding	Perampanel is excreted into human breast milk; estimated infant dose is 0.5-1.5% of the maternal weight-adjusted dose. M/P ratio unknown. In breastfed infants, monitor for sedation, poor feeding, and developmental milestones. Benefit-risk assessment required; if used, monitor infant closely.
Teratogenic Risk	First trimester: Increased risk of major congenital malformations, including neural tube defects (based on animal studies and limited human data). Second and third trimesters: Associated with potential neurodevelopmental impairment, including reduced IQ scores and increased risk of autism spectrum disorder. Avoid if possible; consider alternative therapy.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Dizziness
Serious Effects

Absolute Contraindications

["Hypersensitivity to perampanel or any component of formulation"]

Clinical Precautions

Precautions

["Nervous system effects: serious adverse reactions including ataxia, somnolence, dizziness, vertigo, and abnormal gait","Psychiatric symptoms: aggression, hostility, irritability, anger, and homicidal ideation","Suicidal thoughts and behavior: increased risk with antiepileptic drugs","Abuse potential: may cause euphoria; monitor for signs of abuse","Risk of falls due to dizziness and gait disturbance","Withdrawal: taper gradually to avoid increased seizure frequency"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…