Cenobamate

Indications

Cenobamate is used for: Partial-onset Seizures

Adult Dose

Partial-onset Seizures Indicated for treatment of partial-onset seizures as either monotherapy or adjunctive therapy Dose and titration schedule Do not exceed recommended dosage and titration, owing to potential for serious adverse reactions 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 Hepatic impairment Mild-to-moderate (Child-Pugh 5-9): Not to exceed 200 mg/day; additional dosage reduction may be necessary Severe: Not recommended

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment Mild, moderate, or severe: Caution advised; consider dosage reduction End-stage renal disease: Not recommended

Administration

Administer at any time with or without food Swallow tablet whole with liquid; do not crush or chew

Contra Indications

Hypersensitivity Familial short QT syndrome (SQTS)

Precautions

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) 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 Neurological adverse reactions Dose-dependent increases in somnolence and fatigue-related adverse reactions (somnolence, fatigue, asthenia, malaise, hypersomnia, sedation, and lethargy) observed in approximately one third of patients during clinical trials Dose-dependent adverse reactions related to dizziness and disturbance in gait and coordination (dizziness, vertigo, balance disorder, ataxia, nystagmus, gait disturbance, abnormal coordination) observed in up to ~50% of patients observed in clinical trials Cognitive dysfunction (ie, memory impairment, disturbance in attention, amnesia, confusional state, aphasia, speech disorders, slowness of thought, disorientation, psychomotor retardation) observed Visual changes (eg, diplopia, blurred vision, and impaired vision) observed Warn patients against engaging in hazardous activities requiring mental alertness until the effects of cenobamate are known

Pregnancy-Lactation

Pregnancy Data are unavailable on the developmental risk associated with use of cenobamate in pregnant women Animal studies Administration during pregnancy or throughout pregnancy and lactation resulted in adverse effects on development (increased embryofetal mortality, decreased fetal and offspring body weights, neurobehavioral and reproductive impairment in offspring) at clinically relevant drug exposures Contraception Cenobamate may decrease plasma concentrations of oral contraceptives Women of reproductive potential concomitantly using oral contraceptives should use additional or alternative nonhormonal birth control Lactation Data are unavailable on the presence in human milk, effects on breastfed infants, or effects on milk production

Interactions

CNS depressants and alcohol Coadministration with other CNS depressants, including alcohol, may increase risk of neurological adverse reactions, including sedation and somnolence Effect of cenobamate on other drugs Lamotrigine or carbamazepine: Plasma levels decreased; potential for reduced efficacy of these drugs; increase dosage of lamotrigine or carbamazepine, as needed Phenytoin: Plasma levels increased; owing to potential 2-fold increase in phenytoin levels, gradually decrease phenytoin dosage by up to 50% as cenobamate is being titrated Phenobarbital, clobazam (ie, desmethyl-clobazam active metabolite): Plasma levels increased; potential for increased adverse reactions from these drugs; consider dose reduction of phenobarbital or clobazam, as clinically appropriate Oral contraceptives: Plasma levels decreased; potential for reduced efficacy of oral contraceptives; women should use additional contraceptive or a nonhormonal birth control method while taking cenobamate

Adverse Effects

Side effects of Cenobamate :

Mechanism of Action

Exact mechanism of action unknown It is thought to work by reducing repetitive neuronal firing by inhibiting voltage-gated sodium currents; it is also a positive allosteric modulator of the GABA ion channel