Drug information of cenobamate

cenobamate

Drug group: Anticonvulsants

Cenobamate is used to treat partial-onset seizures in adults.

Mechanism of effect

Cenobamate inhibits voltage gated sodium channels and is a positive GABAA modulator. However, the exact mechanism of action remains unknown. Inhibition of voltage gated sodium channels increases the threshold for generating action potentials and decreases the number of action potentials

Pharmacodynamic

The mechanism of cenobamate is unknown, however it modulates GABAA and inhibit voltage gated sodium channels. Cenobamate is given once daily and so it has a long duration of action. The therapeutic window is wide as doses of 750mg can be well tolerated. Patients should be counselled regarding the risk of DRESS syndrome, QT interval shortening, suicidal behavior, and neurological adverse effects.

Pharmacokinetics

absorption: Cenobamate is 88% orally bioavailable with a Tmax of 1-4 hours. A high fat meal does not significantly impact the pharmacokinetics of cenobamate.
volume of distribution: The apparent volume of distribution of cenobamate is 40-50L.
protein binding: Cenobamate is 60% protein bound in plasma, mainly serum albumin.
metabolism: Data regarding the metabolism of cenobamate is lacking, however it is mostly glucuronidated by UGT2B7 and UGT2B4 or oxidized by a number of cytochromes.
Route of elimination: Cenobamate is 87.8% eliminated in the urine and 5.2% in the feces.
Half-life: The terminal half life of cenobamate is 50-60h.

Drug indications

Partial Onset Seizures

Indicated for treatment of partial-onset seizures as either monotherapy or adjunctive therapy

Dosage

  • Weeks 1-2: 12.5 mg PO qDay initially
  • Titration dose
    • Weeks 3-4: 25 mg PO qDay
    • Weeks 5-6: 50 mg PO qDay
    • Weeks 7-8: 100 mg PO qDay
    • Weeks 9-10 150 mg PO qDay
  • Maintenance dose
    • Week 11 and thereafter: 200 mg PO qDay
  • Maximum dose
    • Based on clinical response and tolerability, dose may be increased above 200 mg by increments of 50 mg/day q2week to 400 mg PO qDay if needed

Drug contraindications

hypersensitivity to drug or its components.

Familial short QT syndrome (SQTS)

Alerts

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, reported; DRESS has occurred, including 1 fatality, when cenobamate was titrated rapidly (weekly or faster titration)
QT shortening >20 msec (31-66%) observed in clinical trials compared with placebo (6-17%); QTc reduction <300 msec not observed; contraindicated in patients with familial SQTS
Antiepileptic drugs (AEDs), including cenobamate, increase risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor for emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
Similar to most AEDs, discontinue cenobamate gradually, owing to risk of increased seizure frequency and status epilepticus; may consider rapid discontinuation because of a serious adverse event

Pregnancy level

Data are unavailable on the developmental risk associated with use of cenobamate in pregnant women

Breast feeding warning

Data are unavailable on the presence in human milk, effects on breastfed infants, or effects on milk production

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