Cenobamate

XCOPRI is indicated for the treatment of partial-onset seizures in adult patients.

The precise mechanism by which cenobamate exerts its therapeutic effects in patients with partial-onset seizures is unknown. Cenobamate has been demonstrated to reduce repetitive neuronal firing by inhibiting voltage-gated sodium currents. It is also a positive allosteric modulator of the γ-aminobutyric acid (GABA A ) ion channel.

Prior to initiating XCOPRI, obtain serum transaminases (ALT and AST) and total bilirubin, if not recently available (i.e., within 3 months), to establish baseline liver function. The recommended initial dosage of XCOPRI is 12.5 mg once daily, titrated to the recommended maintenance dosage of 200 mg once daily. The recommended titration schedule should not be exceeded. The maximum dosage is 400 mg once daily. Hepatic impairment: For patients with mild or moderate hepatic impairment, the maximum recommended dosage is 200 mg once daily. XCOPRI can be taken whole or the tablets can be crushed. The crushed tablet can be mixed with water and either administered by mouth as an oral suspension or administered via a nasogastric tube.

XCOPRI is contraindicated in patients with: Hypersensitivity to cenobamate or any of the inactive ingredients in XCOPRI Familial Short QT syndrome Hypersensitivity to cenobamate or any of the inactive ingredients in XCOPRI. Familial Short QT syndrome.

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity: Discontinue if no alternate etiology. QT Shortening: Use caution when administering XCOPRI with other drugs that shorten the QT interval. Suicidal Behavior and Ideation: Monitor patients for suicidal behavior and ideation. Liver Injury: Clinically significant liver injury has occurred. Obtain serum transaminases (ALT and AST) and total bilirubin before initiating XCOPRI, and during treatment if clinically indicated. Discontinue XCOPRI in patients with evidence of liver injury in the absence of an alternative etiology. Neurological Adverse Reactions: Monitor for somnolence and fatigue and advise patients not to drive or operate machinery until they have gained sufficient experience on XCOPRI. Concomitant use with other CNS depressants or alcohol may have additive effects.

The following serious adverse reactions are described in more detail in the Warnings and Precautions section of the labeling: Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity QT Shortening Suicidal Behavior and Ideation Liver Injury Neurological Adverse Reactions Withdrawal of Antiepileptic Drugs The most common adverse reactions in patients receiving XCOPRI (at least 10% for XCOPRI and more frequently than placebo) include somnolence, dizziness, fatigue, diplopia, and headache.

Phenytoin: Gradually decrease phenytoin dosage by up to 50%. Phenobarbital and Clobazam: Reduce dosage as needed when used concomitantly with XCOPRI. Lamotrigine, Carbamazepine: Increase dosage as needed when used concomitantly with XCOPRI. CYP2B6 and CYP3A Substrates: Increase dosage as needed when used concomitantly with XCOPRI. CYP2C19 Substrates: Reduce dosage as needed when used concomitantly with XCOPRI. Oral Contraceptives: Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with XCOPRI. Women should use additional or alternative non-hormonal birth control.

Store XCOPRI tablets at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F).