Controlled Substance Schedule: V
Partial-onset seizures (as monotherapy or adjunctive therapy).
Inhibits voltage-gated sodium channels, reducing repetitive neuronal firing. Also acts as a positive allosteric modulator of GABAA ion channels.
Decreased incidence of seizures.
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%).
Half-life: 50–60 hr.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||1–4 hr||24 hr|
- Familial short QT syndrome;
- End-stage renal disease on hemodialysis;
- Severe hepatic impairment.
Use Cautiously in:
- All patients (may ↑ risk of suicidal thoughts/behaviors)
- Mild, moderate, or severe renal impairment (consider ↓ dose)
- Mild or moderate hepatic impairment
- OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
- Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
- Pedi: Safety and effectiveness not established in children.
- Geri: Start with lowest dose in older adults due to age-related renal and/or hepatic impairment.
Adverse Reactions/Side Effects
CV: QT INTERVAL SHORTENING, palpitations
Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), pruritus, rash
EENT: diplopia, blurred vision, nystagmus, pharyngitis, vertigo, visual impairment
F and E: hyperkalemia
GI: abdominal pain, constipation, diarrhea, dry mouth, dysgeusia, dyspepsia, ↑ liver enzymes, nausea, vomiting
GU: dysmenorrhea, urinary tract infection, pain
Metabolic: ↓ appetite, ↓ weight
Neuro: SUICIDAL THOUGHTS/BEHAVIORS, dizziness, headache, somnolence, amnesia, aphasia, attention disturbance, confusion, disorientation, dysarthria, euphoria, irritability, memory impairment, slowness of thoughts, ataxia, tremor
Resp: dyspnea, hiccups
Misc: fatigue, physical dependence
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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 non-hormonal 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.
PO (Adults): Mild or moderate hepatic impairment– Not to exceed 200 mg once daily.
Tablets: 12.5 mg, 25 mg, 50 mg, 100 mg, 150 mg, 200 mg
- Assess location, duration, and characteristics of seizure activity.
Monitor for signs and 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 symptoms occur, discontinue cenobamate. immediately.
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 first 4 wk of therapy.
- Risk for injury (Side Effects)
- PO Administer once daily without regard to food. Swallow tablets whole; do not crush, break or chew.
- Instruct patient to take cenobamate as directed. Do not stop abruptly; dose should be gradually decreased 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 professional if signs and symptoms of DRESS, QT shortening (prolonged heart palpitations, loss of consciousness) or neurological adverse reactions occur.
Advise patient and family to notify health care professional 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 increase in activity and talking; other unusual changes in behavior or mood or if skin rash occur.
- Instruct patient to consult with health care professional before drinking alcohol.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
- Rep: Advise female patients to notify health care professional if pregnancy is planned or suspected or if breast feeding. Advise women of reproductive potential using oral contraceptives to use additional or alternative non-hormonal birth control. Encourage pregnant patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334; information is available at www.aedpregnancyregistry.org.
- Advise patient to carry identification describing disease process and medication regimen at all times.
Decreased incidence of seizures.