Cenobamate

Cenobamate is a prescription medicine used for the treatment of partial-onset seizures.

• Cenobamate is available under the following different brand names: Xcopri

Adult dosage

Tablet (Schedule V)

• 12.5mg
• 25mg
• 50mg
• 100mg
• 150mg
• 200mg

Partial-onset Seizures

Adult dosage

• Dose and titration schedule
  • Do not exceed recommended dosage and titration, owing to the potential for serious adverse reactions
  • Weeks 1-2: 12.5 mg PO qDay initially
• Titration dose
  • Weeks 3-4: 25 mg orally every day
  • Weeks 5-6: 50 mg orally every day
  • Weeks 7-8: 100 mg orally every day
  • Weeks 9-10 150 mg orally every day
• Maintenance dose
  • Week 11 and thereafter: 200 mg orally every day
• Maximum dose
  • Based on clinical response and tolerability, the dose may be increased above 200 mg by increments of 50 mg/day every 2 weeks to 400 mg orally every day if needed

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Cenobamate include:

• drowsiness,
• dizziness,
• fatigue,
• double vision, and
• headache.

Serious side effects of the Cenobamate include:

• fast or pounding heartbeats, fluttering in the chest, and sudden dizziness,;
• feeling very weak or tired;
• severe muscle pain;
• fever, swollen glands, sore throat; unusual bruising or bleeding;
• painful sores in the mouth or around the eyes;
• swelling in the face, mouth, or throat;
• trouble breathing or swallowing;
• hives or a rash;
• yellowing of your skin or eyes;
• any infection or illness that does not get better; or
• nervous system problems--dizziness, trouble walking, loss of coordination, vision problems, drowsiness, tiredness, problems with thinking or memory.

Rare side effects of the Cenobamate include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Cenobamate has severe interactions with the following drug:
  • mavacamten
• Cenobamate has serious interactions with the following drugs:
  • ganaxolone
  • lumateperone
  • vonoprazan
• Cenobamate has moderate interactions with at least 401 other drugs.
• Cenobamate has minor interactions with the following drugs:
  • stiripentol
  • voriconazole

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity
• Familial short QT syndrome (SQTS)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Cenobamate?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Cenobamate?”

Cautions

• Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity, was reported; DRESS has occurred, including 1 fatality, when cenobamate was titrated rapidly (weekly or faster titration)
• QT shortening of more than 20 msec (31-66%) was observed in clinical trials compared with placebo (6-17%); QTc reduction below 300 msec not observed; contraindicated in patients with familial SQTS
• Antiepileptic drugs (AEDs), including cenobamate, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication; monitor for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior
• Similar to most AEDs, discontinue cenobamate gradually, owing to the risk of increased seizure frequency and status epilepticus; may consider rapid discontinuation because of a serious adverse event
• Neurological adverse reactions
  • Dose-dependent increases in somnolence and fatigue-related adverse reactions (somnolence, fatigue, asthenia, malaise, hypersomnia, sedation, and lethargy) were observed in approximately one-third of patients during clinical trials
  • Dose-dependent adverse reactions related to dizziness and disturbance in gait and coordination (dizziness, vertigo, balance disorder, ataxia, nystagmus, gait disturbance, abnormal coordination) were observed in up to ~50% of patients observed in clinical trials
  • Cognitive dysfunction (i.e., memory impairment, disturbance in attention, amnesia, confusional state, aphasia, speech disorders, slowness of thought, disorientation, psychomotor retardation) observed
  • Visual changes (e.g., diplopia, blurred vision, and impaired vision) observed
  • Warn patients against engaging in hazardous activities requiring mental alertness until the effects of cenobamate are known
• Drug interaction overview
  • Effect of cenobamate on other drugs
    • Lamotrigine or carbamazepine: Plasma levels decreased; potential for reduced efficacy of these drugs; increase dosage of lamotrigine or carbamazepine, as needed
    • Phenytoin: Plasma levels increased; owing to a potential 2-fold increase in phenytoin levels, gradually decrease phenytoin dosage by up to 50% as cenobamate is being titrated
    • Phenobarbital, clobazam (ie, desmethyl-clobazam active metabolite): Plasma levels increased; potential for increased adverse reactions from these drugs; consider a dose reduction of phenobarbital or clobazam, as clinically appropriate
    • CYP2B6 or CYP3A substrates: Plasma levels decreased; potential for reduced efficacy of these drugs; increase dosage of CYP2B6 or CYP3A4 substrates, as needed
    • Oral contraceptives: Plasma levels decreased; potential for reduced efficacy of oral contraceptives; women should use additional contraceptive or a nonhormonal birth control method while taking cenobamate
    • CYP2C19 substrates: Plasma levels increased; potential for increased risk of adverse reactions from these drugs; consider dosage reduction of CYP2C19 substrates, as clinically appropriate
  • Drugs that shorten QT interval
    • Cenobamate can shorten QT interval; therefore, caution when administering with other drugs that shorten QT interval (e.g., rufinamide)
  • CNS depressants and alcohol
    • Coadministration with other CNS depressants, including alcohol, may increase the risk of neurological adverse reactions, including sedation and somnolence

Pregnancy and Lactation

• Data are unavailable on the developmental risk associated with the use of cenobamate in pregnant women
• Encourage women to enroll in the North American Antiepileptic Drug (NAAED) pregnancy registry at 1-888-233-2334 or http://www.aedpregnancyregistry.org
• Contraception
  • Cenobamate may decrease plasma concentrations of oral contraceptives
  • Women of reproductive potential concomitantly using oral contraceptives should use additional or alternative nonhormonal birth control
• Lactation
  • Data are unavailable on the presence of human milk, effects on breastfed infants, or effects on milk production