Absorption: Well absorbed (≥88%) following oral administration.
Distribution: Well distributed to extravascular tissues.
Metabolism and Excretion: Primarily metabolized by liver by glucuronidation (via UGT2B7 and UGT2B4) and oxidation (via CYP2E1, CYP2A6, CYP2B6, CYP2C19, and CYP3A4/5). Primarily excreted in urine (88%; <10% as unchanged drug) and feces (5%).
QT interval shortening medications may enhance QT shortening, which can ↑ risk of ventricular arrhythmias and sudden cardiac death; use concurrently with caution.
May ↓ levels and effectiveness of carbamazepine and lamotrigine ; ↑ lamotrigine and carbamazepine doses.
May ↑ levels and risk of toxicity of phenytoin ; ↓ phenytoin by up to 50%.
May ↑ levels and risk of toxicity of phenobarbital and clobazam ; ↓ phenobarbital and clobazam doses as clinically appropriate.
May ↓ levels and effectiveness of CYP2B6 substrates and CYP3A substrates ; ↑ dose of CYP2B6 or CYP3A substrate as clinically appropriate.
May ↓ levels and effectiveness of oral hormonal contraceptives ; advise women of reproductive potential to use additional or alternative nonhormonal contraceptive method.
May ↑ levels and risk of toxicity of CYP2C19 substrates ; ↓ dose of CYP2C19 substrate as clinically appropriate.
Use with other CNS depressants, including benzodiazepines, sedative/hypnotics, anxiolytics, opioids, or alcohol, may cause profound sedation.
PO (Adults): 12.5 mg once daily for 2 wk, then 25 mg once daily for 2 wk, then 50 mg once daily for 2 wk, then 100 mg once daily for 2 wk, then 150 mg once daily for 2 wk, then 200 mg once daily. If needed based on clinical response, may ↑ in increments of 50 mg every 2 wk to max dose of 400 mg once daily.
Hepatic Impairment PO (Adults): Mild or moderate hepatic impairment: Not to exceed 200 mg once daily.
Assess location, duration, and characteristics of seizure activity. Institute seizure precautions.
Monitor for signs/symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling) periodically during therapy. May lead to hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis. May resemble an acute viral infection. Eosinophilia is often present. If DRESS occurs, discontinue cenobamate.
Monitor mood changes. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
Assess patient for neurological adverse effects throughout therapy. These adverse effects are categorized as somnolence and fatigue (asthenia), coordination difficulties (ataxia, abnormal gait, or incoordination), cognitive dysfunction (memory impairment, disturbance in attention, amnesia, confusional state, aphasia, speech disorder, slowness of thought, disorientation, psychomotor retardation), visual changes (diplopia, blurred vision, impaired vision), and behavioral abnormalities (agitation, hostility, anxiety, apathy, emotional lability, depersonalization, depression) and usually occur during the 1st 4 wk of therapy.
Monitor for signs/symptoms of hepatotoxicity such as fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools. If liver injury occurs, discontinue cenobamate.
Lab Test Considerations:
Obtain ALT, AST, and bilirubin prior to initiation to establish baseline liver function and promptly in patients who develop clinical signs/symptoms suggestive of hepatic injury.
PO Administer without regard to food. Tablets can be swallowed whole or crushed to make a suspension.
To prepare a suspension, crush the required number of tablets in a cup, and then mix with 25 mL of water. Swirl gently. Administer immediately. Rinse the cup with 25 mL of water to ensure no residual medication remains in the cup and administer. If drug particles remain, rinse the cup with another 25 mL and administer. For nasogastric administration, draw up suspension into a syringe, swirl gently, and administer through nasogastric tube. Visually confirm no particles are left in the syringe; if particles remain, rinse syringe with 10 mL of water again. Repeat once more if particles remain.
Explain the purpose and side effects of cenobamate. Instruct patient to take as directed. Do not stop abruptly; dose should be gradually ↓ over 2 wk. Advise patient to read the Medication Guide prior to starting therapy and with each Rx refill in case of changes.
May cause dizziness and somnolence. Caution patient to avoid driving or activities requiring alertness until response to medication is known. Do not resume driving until physician gives clearance based on control of seizure disorder.
Advise patient to notify health care provider if signs/symptoms of DRESS, skin rash, QT shortening (prolonged heart palpitations, loss of consciousness), or neurological adverse reactions occur.
Advise patient and family to notify health care provider if thoughts about suicide or dying, attempts to commit suicide, new or worse depression, new or worse anxiety, feeling very agitated or restless, panic attacks, trouble sleeping, new or worse irritability, acting aggressive, being angry or violent, acting on dangerous impulses, an extreme ↑ in activity and talking, or other unusual changes in behavior or mood occur. Instruct patient to call the National Suicide Prevention Lifeline at 1-800-273-8255 or visit www.988lifeline.org if they experience suicidal thoughts.
Instruct patient to consult with health care provider before drinking alcohol.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Instruct patient to notify health care provider of medication regimen prior to treatment or surgery.
Advise patient to carry identification describing disease process and medication regimen at all times.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Advise women using oral contraceptives to use additional or alternative nonhormonal birth control. Encourage pregnant patients to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.