Cenobamate
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omid Afkhami-Ardakani
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Overview
Cenobamate is a Sodium Channel Inhibitor that is FDA approved for the treatment of partial-onset seizures in adult patients.. Common adverse reactions include dizziness, somnolence, fatigue, headache, nausea, constipation, balance disorder, and rash..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Titration Schedule:
Weeks 3–4: 25 mg once daily.
Weeks 5–6: 50 mg once daily.
Weeks 7–8: 100 mg once daily.
Weeks 9–10: 150 mg once daily.
Week 11 and beyond: 200 mg once daily (maintenance dose).
Maximum Dose: 400 mg once daily, with increments of 50 mg every two weeks based on clinical response and tolerability.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cenobamate in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cenobamate in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Cenobamate FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Cenobamate in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Cenobamate in pediatric patients.
Contraindications
Patients with familial short QT syndrome.
Known hypersensitivity to cenobamate or any of its components
Warnings
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Monitor for signs such as fever, rash, lymphadenopathy, and organ dysfunction.
QT Interval Shortening: Avoid use in patients with familial short QT syndrome.
Suicidal Behavior and Ideation: Monitor for emergence or worsening of depression, suicidal thoughts, or behavior.
Neurological Adverse Reactions: Dizziness, somnolence, and fatigue may occur; caution patients about operating machinery or driving.
Adverse Reactions
Clinical Trials Experience
Nervous System Disorders:
Dizziness (33%)
Somnolence (37%)
Fatigue (24%)
Headache
Gastrointestinal Disorders:
Nausea
Constipation
General Disorders:
Balance disorder
Skin and Subcutaneous Tissue Disorders:
Rash
Postmarketing Experience
There is limited information regarding Cenobamate Postmarketing Experience in the drug label.
Drug Interactions
CYP3A4 and CYP2B6 Induction: May decrease plasma concentrations of drugs metabolized by these enzymes (e.g., midazolam, bupropion).
CYP2C19 Inhibition: May increase plasma concentrations of drugs metabolized by this enzyme (e.g., omeprazole).
Oral Contraceptives: May decrease efficacy; advise use of alternative non-hormonal contraceptive methods.
CNS Depressants: Concomitant use with alcohol or other CNS depressants may enhance sedative effects.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Cenobamate in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Cenobamate in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Cenobamate during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Cenobamate in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Cenobamate in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Cenobamate in geriatric settings.
Gender
There is no FDA guidance on the use of Cenobamate with respect to specific gender populations.
Race
There is no FDA guidance on the use of Cenobamate with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Cenobamate in patients with renal impairment.
Hepatic Impairment
Mild to moderate impairment: Maximum recommended dose is 200 mg once daily.
Severe impairment: Use not recommended.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Cenobamate in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Cenobamate in patients who are immunocompromised.
Administration and Monitoring
Administration
Oral tablets; swallow whole. Neurology live
Can be taken with or without food.
Tablets may be crushed and mixed with water for oral suspension or administration via nasogastric tube.
Monitoring
Monitor for signs of DRESS, suicidal behavior, and CNS depression.
Regularly assess seizure frequency and severity.
Monitor plasma levels of concomitant medications as needed due to potential drug interactions.
IV Compatibility
There is limited information regarding the compatibility of Cenobamate and IV administrations.
Overdosage
n the event of an overdose, patients may experience:
Exaggerated central nervous system (CNS) effects: Drowsiness, dizziness, fatigue.
Cardiac effects: Potential alterations in heart rhythm, including QT interval changes.
Management
Supportive care: Monitor vital signs and provide symptomatic treatment.
Cardiac monitoring: Due to potential QT interval shortening, continuous ECG monitoring may be warranted.
Consult Poison Control.
Pharmacology
There is limited information regarding Cenobamate Pharmacology in the drug label.
Mechanism of Action
Cenobamate is a novel antiseizure medication that exerts its effects through two primary mechanisms:
Inhibition of Persistent Sodium Currents: Cenobamate preferentially inhibits the persistent component of voltage-gated sodium currents, which are often implicated in the hyperexcitability of neurons associated with seizures.
Positive Allosteric Modulation of GABAA Receptors: It acts as a positive allosteric modulator at GABAA receptors, enhancing inhibitory neurotransmission independently of the benzodiazepine binding site.
Structure
There is limited information regarding Cenobamate Structure in the drug label.
Pharmacodynamics
Cenobamate exhibits dose-dependent reductions in seizure frequency. In clinical trials, higher doses correlated with greater seizure control, including increased rates of seizure freedom. Its dual mechanism enhances both the inhibition of excitatory currents and the potentiation of inhibitory neurotransmission.
Pharmacokinetics
Absorption: Cenobamate is well-absorbed orally, with a bioavailability of ≥88%.
Peak Plasma Concentration (Tmax): Occurs approximately 1–4 hours post-dose.
Protein Binding: Approximately 60%, primarily to albumin.
Metabolism: Primarily metabolized via glucuronidation (UGT2B7 and UGT2B4) and to a lesser extent by CYP enzymes (CYP2E1, CYP2A6, CYP2B6, CYP2C19, and CYP3A4).
Elimination Half-Life: Approximately 50–60 hours, supporting once-daily dosing.
Excretion: Mainly excreted via urine; minimal fecal excretion.
Nonclinical Toxicology
There is limited information regarding Cenobamate Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Cenobamate Clinical Studies in the drug label.
How Supplied
Dosage Forms: Film-coated tablets. Available in 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, and 200 mg tabletes.
Storage
Temperature: Store at 20°C to 25°C (68°F to 77°F).
Excursions: Permitted between 15°C to 30°C (59°F to 86°F).
Environment: Keep in a dry place, away from moisture and direct light.
Safety: Store out of reach of children and pets; consider using a locked storage area.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Administration:
Take once daily, with or without food.
Tablets can be swallowed whole or crushed and mixed with water for oral suspension or nasogastric tube administration.
Dose Titration:
Begin with 12.5 mg once daily, increasing every two weeks as directed.
Do not exceed the prescribed dose without consulting a healthcare provider.
Adverse Effects:
Common: Drowsiness, dizziness, fatigue, headache.
Serious: Signs of hypersensitivity (e.g., rash, fever), suicidal thoughts, QT interval shortening.
Drug Interactions:
Inform about all medications being taken, including over-the-counter drugs and supplements.
Use non-hormonal contraception, as cenobamate may reduce the effectiveness of hormonal contraceptives.
Alcohol and CNS Depressants:
Avoid alcohol and other CNS depressants unless approved by a healthcare provider.
Pregnancy and Lactation:
Discuss potential risks if pregnant or planning to become pregnant.
Consider enrolling in the North American Antiepileptic Drug Pregnancy Registry.
Missed Dose:
If a dose is missed, take it as soon as remembered unless it's close to the next dose.
Do not double the next dose. European Commission
Discontinuation:
Do not abruptly stop taking cenobamate; tapering under medical supervision is necessary to prevent increased seizure risk.
Precautions with Alcohol
It is advised to avoid or limit alcohol consumption while taking cenobamate.
Brand Names
Xcopri® is the only approved brand name for cenobamate.
Look-Alike Drug Names
There is limited information regarding Cenobamate Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.