Dosing and uses of Aptiom (eslicarbazepine acetate)
Adult dosage forms and strengths
tablet
- 200mg
- 400mg
- 600mg
- 800mg
Partial-Onset Seizures
Indicated for partial-onset seizures as monotherapy or adjunctive therapy
InitiaL
- 400 mg PO qDay
- For some patients, treatment may be initiated at 800 mg qDay if the need for additional seizure reduction outweighs an increased risk of adverse reactions during initiation
Titration & maintenance
- Increase dose by weekly increments of 400-600 mg, based on clinical response and tolerability
- Recommended maintenance dose is 800-1600 mg once daily
- Monotherapy: Consider 800 mg/day maintenance dose in patients unable to tolerate 1200 mg/day
- Adjunctive therapy: 1600 mg/day should be considered in patients who did not achieve a satisfactory response with 1200 mg/day
Dosage modifications
Do not take adjunctively with oxcarbazepine
Coadministration with enzyme-inducing AEDs (eg, carbamazepine, phenytoin, phenobarbital, primidone): May need to increase eslicarbazepine dose
Renal impairment
- Moderate-to-severe (CrCl <50 mL/min): Reduce the initial, titration, and maintenance doses by 50%; may adjust titration and maintenance doses according to clinical response
Hepatic impairment
- Mild-to-moderate: No dosage adjustment required
- Severe: Not recommended (not studied)
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Aptiom (eslicarbazepine acetate) adverse (side) effects
>10%
Dizziness (20-28%)
Somnolence (11-18%)
Nausea (10-16%)
Headache (13-15%)
Diplopia (9-11%)
1-10%
Vomiting (6-10%)
Fatigue (4-7%)
Blurred vision (5-6%)
Ataxia (4-6%)
Vertigo (2-6%)
Diarrhea (2-4%)
Tremor (2-4%)
Balance disorder (3%)
Asthenia (2-3%)
Falls (1-3%)
Depression (1-3%)
Rash (1-3%)
Constipation (2%)
Abdominal pain (2%)
Gait disturbance (2%)
UTI (2%)
Hyponatremia (2%)
Insomnia (2%)
Visual impairment (1-2%)
Gastritis (1-2%)
Peripheral edema (1-2%)
Dysarthria (1-2%)
Memory impairment (1-2%)
Nystagmus (1-2%)
Cough (1-2%)
Hypertension (1-2%)
Warnings
Contraindications
Hypersensitivity to eslicarbazepine or oxcarbazepine
Cautions
See FDA warning on potential suicidal behavior; monitor patients for notable changes in behavior that might be associated with suicidal thoughts or depression (notify health-care provider immediately if symptoms occur)
Serious dermatologic reactions reported, including Stevens-Johnson syndrome (SJS); serious and sometimes fatal dermatologic reactions, including toxic epidermal necrolysis (TEN) and SJS, have been reported in patients using oxcarbazepine or carbamazepine which are chemically related
Drug reaction with eosinophilia and systemic symptoms (DRESS) reported; DRESS may be fatal or life-threatening, and although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection
Anaphylactic reactions and angioedema: Monitor for breathing difficulties or swelling; discontinue if another cause cannot be established
Hyponatremia: Monitor sodium levels in patients at risk or patients experiencing hyponatremia symptoms
Neurological adverse reactions: Monitor for dizziness, disturbance in gait and coordination, somnolence, fatigue, cognitive dysfunction, and visual changes; caution when driving or operating machinery
Discontinuing: Withdraw gradually to minimize risk of increased seizure frequency and status epilepticus
Drug-induced liver injury: Discontinue with jaundice or evidence of significant liver injury
Dose-dependent decreases in serum T3 and T4 (free and total) values reported
Pregnancy and lactation
Pregnancy category: C
When eslicarbazepine acetate was administered PO (65, 125, 150, 250, 350, 650 mg/kg/day) to pregnant mice throughout organogenesis, increased incidences of fetal malformations was observed at all doses and fetal growth retardation was observed at the mid and high doses; delayed sexual maturation and a neurological deficit (decreased motor coordination) were observed at 250 mg/kg/day
North American Antiepileptic Drug Pregnancy Registry: 1-888-233-2334
Lactation: Unknown if distributed in human breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Aptiom (eslicarbazepine acetate)
Mechanism of action
Antiepileptic drug; eslicarbazepine acetate is a prodrug that is activated to eslicarbazepine (S-licarbazepine), the major active metabolite of oxcarbazepine
Stabilizes neuronal membranes by blocking Na+ channels; this may inhibit repetitive firing and may decrease the propagation of synaptic impulses; may also increase potassium conductance and modulate the activity of high-voltage activated calcium channels
Absorption
Bioavailability: >90%
Peak plasma concentration: 1-4 hr (as eslicarbazepine [major metabolite] of prodrug)
Distribution
Protein bound: <40%
Vd: 61L
Metabolism
Rapidly and extensively metabolized to its major active metabolite (eslicarbazepine) by hydrolytic first-pass metabolism
Eslicarbazepine corresponds to 91% of systemic exposure
Systemic exposure of minor active metabolites: (R)-licarbazepine 5%, oxcarbazepine 1%
Systemic exposure of inactive glucuronide ~1%
Moderate CYP2C19 inhibitor; no apparent autoinduction
Elimination
Half-life: 13-20 hr
Excretion: >90% urine; two-thirds as unchanged form and one-third as glucuronide conjugate
Administration
Instructions
May take with or without food
May swallow table whole or crush
Discontinuation: Reduce dose gradually and avoid abrupt discontinuation to minimize risk of increased seizure frequency and status epilepticus
