Dosage and Administration of Cenobamat: Recommended Dosage

Administration Route

Cenobamat is available as oral tablets, to be taken once daily.

Tablets should be swallowed whole with liquid, and must not be crushed or chewed.

Administration time is not restricted; the drug can be taken either before or after meals.

Dosage Titration Schedule

Initial dose: For Weeks 1–2 of treatment, 12.5 mg once daily.

Titration phase: Weeks 3–4: Increase to 25 mg once daily.

Weeks 5–6: Increase to 50 mg once daily.

Weeks 7–8: Increase to 100 mg once daily.

Weeks 9–10: Increase to 150 mg once daily.

Recommended maintenance dose: Starting from Week 11, a long-term maintenance dose of 200 mg once daily is recommended.

Maximum dose: If dose escalation is deemed necessary based on clinical response and tolerability assessment, the dose may be increased by 50 mg once daily every two weeks, after maintaining the 200 mg dose for at least two weeks. The maximum daily dose shall not exceed 400 mg once daily.

Dosage Adjustment of Cenobamat

Patients with Hepatic Impairment

For patients with mild to moderate hepatic impairment (Child-Pugh score 5–9), the maximum recommended dose of cenobamat should be reduced to 200 mg once daily, and further dose reduction may need to be considered based on individual conditions.

The use of cenobamat is not recommended for patients with severe hepatic impairment.

Discontinuation Method

Unless immediate discontinuation is required due to serious safety concerns, cenobamat should be tapered gradually when the decision to discontinue treatment is made.

The recommended tapering period should last at least 2 weeks to minimize the risk of increased seizure frequency.

Dosage Adjustment for Drug Interactions

Phenytoin: Concurrent use may double the plasma concentration of phenytoin. During cenobamat titration, the dose of phenytoin should be gradually reduced by up to 50%.

Phenobarbital and clobazam: Concurrent use may increase the risk of adverse reactions. Consider reducing the doses of these drugs as appropriate.

Lamotrigine and carbamazepine: Concurrent use may reduce therapeutic efficacy. Consider increasing the doses of these drugs as appropriate.

Oral contraceptives: Cenobamat may decrease the effectiveness of hormonal oral contraceptives. Female patients should use an additional or alternative non-hormonal contraceptive method during treatment.

Use of Cenobamat in Special Populations

Patients with Renal Impairment

Cenobamat should be used with caution in patients with mild to moderate renal impairment (creatinine clearance 30 to < 90 mL/min) and severe renal impairment (creatinine clearance < 30 mL/min), and dose reduction should be considered.

The use of cenobamat is not recommended for patients with end-stage renal disease undergoing dialysis.

Pregnant and Lactating Women

Pregnancy: Animal studies have demonstrated potential fetal risks. The use of cenobamat during pregnancy requires a careful weighing of benefits against risks.

Lactation: There are no available data regarding whether cenobamat is excreted in human milk or its effects on infants or milk production. A comprehensive assessment should be conducted, taking into account the benefits of breastfeeding for the infant, the mother’s clinical need for the medication, and the potential risks of the drug to the infant.