Cenobamate is a once daily antiepileptic drug with a recommended maintenance dose of 200 mg once daily that may be prescribed as monotherapy or as adjunctive therapy.
The FDA approved cenobamate (Xcopri) in 2019 for the treatment of partial-onset seizures in adult patients 18 years of age or older.1 A partial onset seizure is an uncontrolled activation of neurons in a limited area of the brain. Many patients require up to 3 concomitant antiepileptic drugs and may still have breakthrough seizures.
Cenobamate is a once daily antiepileptic drug with a recommended maintenance dose of 200 mg once daily that may be prescribed as monotherapy or as adjunctive therapy.2 Cenobamate was evaluated in 2 multicenter studies and was shown to cause a statistically significant 2 times greater reduction in seizures compared to placebo in as many as 1 in 5 patients.2
Mode of action3
Cenobamate is a positive allosteric modulator of the -aminobutyric acid (GABAA) ion channel.
The exact mechanism of action of the drug is unknown; however, it has been shown to inhibit voltage-gated sodium channels, causing a reduction in repetitive neuronal firing.
Dosage and Administration3
Cenobamate is taken orally once a day with or without food. Patients should swallow the tablets whole and never crush or chew them.
- Initial Dosage
- Weeks 1 and 2: 12.5 mg once a day
- Titration Dosage
- Weeks 3 and 4: 5 mg once a day
- Weeks 5 and 6: 50 mg once a day
- Weeks 7 and 8: 100 mg once a day
- Weeks 9 and 10: 150 mg once a day
- Maintenance dose
- Weeks 11 and beyond: 200 mg once a day
FDA-approved labeling recommends a maximum dose of 400 mg once a day as needed based on the patient’s response to the medication. It also indicates that clinicians should increase doses every 2 weeks in increments of no more than 50 mg per day up to a maximum dose of 400 mg.
The dosage of cenobamate should be gradually reduced over at least 2 weeks to reduce the risk of seizures and status epilepticus. Rapid discontinuation may be considered in cases of serious adverse events (AEs).
The most common side effects were drowsiness, dizziness, fatigue, double vision and headache.
Warnings and Precautions3
Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS), including one fatality, has been reported when patients taking cenobamate are titrated too rapidly. No DRESS events were reported when prescribers started cenobamate at 12.5 mg daily and titrated at the appropriate 2 week interval.
Prescribers should monitor patients for signs and symptoms of DRESS. Such symptoms include fever, rash, and lymphadenopathy, along with other organ involvement.
Cenobamate may shorten the QT interval. Prescribers should closely monitor patients taking other drugs that shorten the QT interval in addition to cenobamate.
Several anti-seizure drugs can increase the risk of suicidal thoughts and behavior. Patients treated with cenobamate are also at risk and prescribers should monitor patients for worsening depression and suicidal ideation or behavior.
Cenobamate is contraindicated in patients with familial short QT syndrome and in patients with known hypersensitivity to any component of the drug.
Pregnancy and breastfeeding1.3
Cenobamate should be avoided during pregnancy due to a lack of adequate data on developmental risk. There are currently no data on the presence of the drug in breast milk.
Prescribers and patients should discuss the developmental and health benefits of breast-feeding, consider the mother’s need for cenobamate and any effects on the infant before breast-feeding.
About the author
Connor Walker, PharmD, is a clinical pharmacist at Yale New Haven Health in Connecticut.
1. Snapshots of Drug Research: Xcopri. US Food and Drug Administration. Accessed May 14, 2022. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-xcopri
2. Xcopri (healthcare professionals). SK Life Sciences. Accessed May 12, 2022 https://www.xcoprihcp.com/
3. Xcopri Prescribing Information. April 2021. Accessed May 12, 2022 https://www.xcopri.com/wp-content/uploads/2021/05/SK_Prescribe_Information_Med_ Guide_Combined.pdf