General

Pronunciation:
es-lye-kar-bay-ze-peen

Trade Name(s)

• Aptiom

Ther. Class.
anticonvulsants

Pharm. Class.
carbamazepine analogues

Indications

Treatment of partial-onset seizures (as monotherapy or adjunctive therapy).

Action

Inhibits voltage-gated sodium channels.

Therapeutic Effect(s):

Decreased incidence and severity of partial-onset seizures.

Pharmacokinetics

Absorption: Eslicarbazepine acetate (the oral dose form) is rapidly converted to eslicarbazepine, its active form which is 90% bioavailable.

Distribution: Enters breast milk, remainder of distribution unknown.

Metabolism and Excretion: Rapidly and extensively metabolized via first-pass hepatic metabolism to its active form (eslicarbazepine); other minor metabolites have anticonvulsant activity. Excreted in urine as unchanged eslicarbazepine and metabolites.

Half-life: 13–20 hr.

TIME/ACTION PROFILE (blood levels†)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity to eslicarbazepine or oxcarbazepine
• Severe hepatic impairment;
• Concomitant use with oxcarbazepine
• OB:  May cause fetal harm
• Lactation: Enters breast milk, avoid breastfeeding.

Use Cautiously in:

• Concurrent use with carbamazepine (↑ risk of adverse reactions);
• Renal impairment (dose adjustment required for CCr <50 mL/min)
• Geri:  Consider age-related ↓ in renal, hepatic and cardiovascular function, concurrent disease states and drug therapies;
• Pedi:   Children <4 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

CNS: SUICIDAL BEHAVIOR/IDEATION, dizziness, drowsiness, fatigue, cognitive dysfunction, depression, headache, insomnia, vertigo

EENT: visual changes

GI: nausea, drug-induced liver injury, vomiting

Derm: STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

Endo: abnormal thyroid function

F and E: hyponatremia

Hemat: agranulocytosis, leukopenia, pancytopenia

Neuro: gait disturbance, tremor

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Carbamazepine  may ↓ levels; when used concomitantly, dosage adjustments of both medications may be needed.
• Phenytoin, phenobarbital, and  primidone  may ↓ levels; may need to ↑ eslicarbazepine dose when used concomitantly.
• May ↓ effectiveness of  hormonal contraceptives  (additional/alternative contraception required).
• May ↑ blood levels of clobazam,  phenytoin  or   omeprazole .
• May induce CYP3A4 enzyme system resulting in ↓ levels of other  drugs metabolized by CYP3A4  including  simvastatin  or  rosuvastatin .
• May alter the response to  warfarin .

Route/Dosage

PO  (Adults)  400 mg once daily initially; may ↑ by 400–600 mg/day on weekly basis to maintenance dosage of 800–1600 mg once daily.

PO  (Children  ≥4 yr and >38 kg) 400 mg once daily initially; may ↑ by 400 mg/day on weekly basis to maintenance dosage of 800–1200 mg once daily.

PO  (Children  ≥4 yr and 32–38 kg) 300 mg once daily initially; may ↑ by 300 mg/day on weekly basis to maintenance dosage of 600–900 mg once daily.

PO  (Children  ≥4 yr and 22–31 kg) 300 mg once daily initially; may ↑ by 300 mg/day on weekly basis to maintenance dosage of 500–800 mg once daily.

PO  (Children  ≥4 yr and 11–21 kg) 200 mg once daily initially; may ↑ by 200 mg/day on weekly basis to maintenance dosage of 400–600 mg once daily.

Renal Impairment 
PO  (Adults)   CCr <50 mL/min– 200 mg once daily initially; may ↑ by 200–300 mg/day on weekly basis to maintenance dosage of 400–800 mg once daily.

Availability

Tablets: 200 mg, 400 mg, 600 mg, 800 mg

Assessment

• Monitor closely for notable changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
• Assess for signs and symptoms of anaphylaxis (rash, dyspnea, laryngeal edema). Discontinue eslicarbazepine and treat symptomatically.
• Monitor for signs and symptoms of hyponatremia (nausea, tiredness, lack of energy, irritability, confusion, muscle weakness or muscle spasms, more frequent or severe seizures.
• Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
• Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations: Monitor hepatic function (AST, ALT, bilirubin) prior to starting and periodically during therapy. Discontinue eslicarbazepine if jaundice or significant liver injury occurs.

• May cause ↓ T3 and T4 (free and total) levels; may not be associated with other abnormal thyroid function tests. Evaluate abnormal thyroid tests clinically.
• Monitor serum sodium and chloride levels periodically during therapy. May cause hyponatremia.
• May cause pancytopenia, agranulocytosis, and leukopenia. Discontinue therapy if hematologic adverse reactions occur.

Potential Diagnoses

• Risk for injury (Adverse Reaction) 

Implementation

• PO  Administer with or without food. Tablets may be swallowed whole or crushed.

Patient/Family Teaching

• Instruct patient to take eslicarbazepine as directed. Do not stop taking without consulting health care professional; dose should be decreased gradually upon discontinuation.
• 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 occur.
• Instruct patients that behavioral changes; swelling of face, eyes, lips or tongue; trouble swallowing or breathing; skin rash; hives; fever; swollen glands; sore throat; painful sores in mouth or around eyes; yellowing of skin or eyes; unusual bleeding or bruising; severe fatigue or weakness; severe muscle pain; signs and symptoms of DRESS; frequent infections or infections that don't go away should be reported to health care professional immediately.
• May cause nervous system problems or cognitive dysfunction (dizziness, trouble walking or coordination, feeling sleepy or tired, trouble concentrating, vision problems, memory impairment, amnesia, speech disorder, slowness of thought). Advise patients to avoid driving or other activities requiring alertness until response to medication is known. May require discontinuation of therapy.
• Inform patient that fever associated with signs or other organ system involvement (rash, lymphadenopathy, hepatic dysfunction) may be related to eslicarbazepine; notify health care professional immediately.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Advise patients to carry identification describing disease and medication regimen at all times.
• Rep:  Advise female patients to use a nonhormonal form of contraception while taking eslicarbazepine, to avoid breastfeeding, and to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Encourage patients who become pregnant to enroll in the North American Antiepileptic Drug Pregnancy Registry. Must be done by patients themselves by calling 1-888-233-2334 or on the website http://www.aedpregnancyregistry.org.
• Emphasize the importance of follow-up lab tests and eye exams to monitor for side effects.

Evaluation/Desired Outcomes

Decreased incidence and severity of partial-onset seizures.