cenobamate: clinical use

Prescribing considerations

• Use only as adjunctive treatment within the licensed adult population.
• Review renal and hepatic function, polypharmacy, contraception, CNS adverse effects and falls risk.
• Use caution with medicines that shorten the QT interval and in older people.

Contraindications and cautions

• Hypersensitivity to cenobamate or an excipient.
• Familial short-QT syndrome.
• Severe hepatic impairment, end-stage renal disease or haemodialysis.

Monitoring

• Check ALT, AST, GGT, alkaline phosphatase and total bilirubin before initiation and during treatment.
• Monitor for DRESS, rash, liver injury, suicidal ideation and neurological adverse effects.
• Review seizure control and adherence.
• Monitor phenytoin and phenobarbital concentrations when co-prescribed; assess clobazam-related adverse effects.
• Reassess interacting medicines when cenobamate is initiated, changed or discontinued.

Clinical pharmacology

Cenobamate positively modulates non-benzodiazepine sites on GABA-A receptors, enhances sodium-channel inactivation and inhibits persistent sodium current. It is extensively metabolised, mainly by glucuronidation, and can induce CYP3A4 and CYP2B6 while inhibiting CYP2C19 and OAT3.

Formulation and product differences

• The selected product is an oval, light-orange film-coated tablet containing lactose.
• Tablets lack a break line and cannot be split accurately.
• Whole tablets and crushed tablets mixed with water have comparable exposure; crushed tablets may be given orally or through a nasogastric tube.
• An initiation pack and multiple tablet strengths are marketed separately.

Tablet

Route: Oral

Strengths: 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg