Cenobamate

Cenobamate is an anti-epileptic drug used for the treatment of partial-onset seizures in adult patients. It is a positive GABA-A modulator which inhibits voltage-gated sodium channels. Inhibition of voltage-gated sodium channels increases the threshold for generating action potentials and decreases the number of action potentials. Its dual, complementary mechanisms of action may contribute to superior anti-seizure activity. Cenobamate can be taken with or without food. The dose is gradually increased (titration) and the maintenance dose is typically 200 mg once daily. If needed based on clinical response and tolerability, the dose may be increased up to 400 mg/day. Common side effects include somnolence, fatigue, dizziness, nausea, constipation, double vision, decreased appetite, and diarrhea. Consult your doctor before use during pregnancy. Avoid driving or operating machinery during treatment.

• Partial-onset seizures in adult patients

Cenobamate is a positive GABA-A modulator which inhibits voltage-gated sodium channels. Inhibition of voltage-gated sodium channels increases the threshold for generating action potentials and decreases the number of action potentials. Its dual, complementary mechanisms of action may contribute to superior anti-seizure activity.

Cenobamate is a positive GABA-A modulator which inhibits voltage-gated sodium channels. Inhibition of voltage-gated sodium channels increases the threshold for generating action potentials and decreases the number of action potentials.

Recommended Dosage for Partial-Onset Seizures in Adults:

Maximum Dosage: If needed based on clinical response and tolerability, the dose may be increased above 200 mg by increments of 50 mg once daily every two weeks to 400 mg once daily.

Renal Dose: Use with caution in mild to severe renal impairment (CrCl 30-90 or <30); consider dose reduction; maximum 300 mg/day. Not recommended in end-stage renal disease or hemodialysis.

Hepatic Dose: Use with caution in mild to moderate hepatic impairment; consider dose reduction; not recommended in severe hepatic impairment.

Cenobamate can be taken with or without food, or as recommended by a physician.

If you miss a dose of Cenobamate, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Common Side Effects:

• Somnolence
• Fatigue
• Dizziness
• Nausea
• Constipation
• Double vision
• Decreased appetite
• Diarrhea
• Weakness

Rare: A very serious allergic reaction to this drug is rare.

• Potential adverse effects such as Multiorgan hypersensitivity reaction (DRESS), QT shortening, and Suicidal thoughts.
• Somnolence and fatigue should be periodically re-evaluated.
• Patients are advised not to drive or operate machinery during cenobamate therapeutic regimen.
• Cenobamate should be gradually withdrawn to minimize the potential of increased seizure frequency.
• Concomitant use with other CNS depressants or alcohol may have additive effects.
• Monitor patients for suicidal behavior and ideation.

• Hypersensitivity to either Cenobamate or to any excipients in Cenobamate.
• Familial Short QT syndrome.

Phenytoin: Gradually decrease phenytoin dosage by up to 50%.

Phenobarbital and Clobazam: Reduce dosage as needed when used concomitantly with Cenobamate.

Lamotrigine, Carbamazepine: Increase dosage as needed when used concomitantly with Cenobamate.

CYP2B6 and CYP3A Substrates: Increase dosage as needed when used concomitantly with Cenobamate.

CYP2C19 Substrates: Reduce dosage as needed when used concomitantly with Cenobamate.

Oral Contraceptives: Effectiveness of hormonal oral contraceptives may be reduced when administered concomitantly with Cenobamate. Women should use additional or alternative non-hormonal birth control.

Information on alcohol consumption with Cenobamate is not available. It is advised to avoid alcohol with Cenobamate as it may increase CNS depressant effects.

There are no adequate and well-controlled studies in pregnant women with the use of Cenobamate. But it may cause fetal harm when administered to a pregnant woman. It should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.

There are no data on the presence of Cenobamate in human milk, the effects of Cenobamate on the breastfed infant, or the effects of Cenobamate on milk production.

The safety and efficacy of cenobamate in children under 18 years have not yet been established.

Start at the low end of the dosing range for elderly patients.

[CAUTION] Renal impairment: Cenobamate should be used with caution and reduction of the target dose may be considered in patients with mild to moderate (CrCl 30-90 ml/min) or severe (CrCl <30 ml/min) renal impairment. The maximum recommended dose for patients with mild, moderate, or severe renal impairment is 300 mg/day. Cenobamate should not be used in patients with end-stage renal disease or patients undergoing hemodialysis.

[CAUTION] Hepatic impairment: Use with caution in patients with mild to moderate hepatic impairment: lower maximum dose and additional dose reduction may be considered. The use of cenobamate in patients with severe hepatic impairment is not recommended.

In the event of overdose, Cenobamate should be discontinued and general supportive treatment given until clinical toxicity has been diminished or resolved.

Do not store above 30°C. Keep away from light and out of the reach of children.

Cenobamate