Cenobamate

XCOPRI

What it isSodium channel blocker and GABA-A positive modulator; focal seizures.

Why this oneIt produces seizure freedom in a substantial minority of refractory patients, which few adjuncts achieve.

What limits itA very slow titration is mandatory to avoid DRESS. QT shortening; it induces CYP3A4 and inhibits CYP2C19.

FDA-approved for

FDA dosing	Population	Start	Target	Max
Partial-onset seizures	Adult	12.5 mg QD	200 mg QD	400 mg QD

Titration Increase per schedule no faster than every 2 weeks; above 200 mg, +50 mg QD every 2 weeks

Renal Mild-severe (CLcr <90): use caution, consider dose reduction; not recommended in ESRD/dialysis (CLcr <15)

Hepatic Mild-moderate (Child-Pugh A-B): max 200 mg QD; severe (C): not recommended

Take once daily with or without food
May swallow whole or crush; crushed tablet mixed with water as oral suspension or given via NG tube
Obtain baseline ALT/AST and total bilirubin before starting
Taper to discontinue

Pregnancy No adequate human data; enroll in NAAED Antiepileptic Drug Pregnancy Registry

Lactation No human milk data; present in rat milk

NO BOXED WARNINGS

Principal riskDRESS unless titration is slow

Cost, est. cash$300–$2,500/month

Generic entry2032 est.

Therapeutic safety burden3 / 4

Overdose danger3 / 4

Weight-gain liability1 / 4

Sedation liability2 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryNot assigned — PLLR-era drug

Defining liabilityDRESS with rapid titration, profound sedation/interactions and QT shortening.

CYP2C19 inhibitor (moderate)

CYP3A4 inducer (moderate)