Aptiom (eslicarbazepine acetate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Eslicarbazepine acetate, a dibenz(b, f)azepine-5-carboxamide derivative, is an anticonvulsant. Eslicarbazepine acetate is a prodrug that is metabolized to eslicarbazepine (S-licarbazepine), the major active metabolite of oxcarbazepine.
Eslicarbazepine acetate, a prodrug of eslicarbazepine, is a dibenzazepine voltage-gated sodium channel (VGSC) blocker; the drug is an anticonvulsant. Eslicarbazepine acetate is structurally similar to 2 other dibenzazepine anticonvulsants, carbamazepine and oxcarbazepine. Eslicarbazepine is the S-enantiomer of racemic licarbazepine, which is the active, 10-monohydroxy metabolite of oxcarbazepine (MHD).
Although the exact mechanism by which eslicarbazepine acetate exerts its anticonvulsant effects has not been fully elucidated, the drug, like carbamazepine and oxcarbazepine, is thought to selectively reduce excitability of rapidly firing neurons by inhibiting voltage-gated sodium channels. Eslicarbazepine appears to preferentially target the inactivated state of the ion channel and exhibits a higher binding affinity for the inactivated state than for the resting state, preventing its return to the active state and thereby reducing repetitive neuronal firing.
Following oral administration, eslicarbazepine acetate is rapidly and extensively metabolized by hydrolytic first-pass metabolism to eslicarbazepine; plasma concentrations of the parent drug remain mostly undetectable. Peak plasma concentrations of eslicarbazepine occur 1-4 hours following oral administration of the drug. Food does not affect the pharmacokinetics of eslicarbazepine acetate.
The drug exhibits linear and dose-proportional pharmacokinetics at recommended dosages. Steady-state concentrations of eslicarbazepine are attained 4-5 days after once-daily dosing. Protein binding of eslicarbazepine is relatively low (less than 40%) and independent of plasma concentration.
Eslicarbazepine accounts for 91% of systemic exposure; systemic exposure to the minor active metabolites of R-licarbazepine and oxcarbazepine is 5 and 1%, respectively, while the inactive glucuronides of these metabolites account for approximately 3% of systemic exposure. Autoinduction of metabolism has not been observed with the drug. Eslicarbazepine and other metabolites are primarily eliminated by renal excretion in the unchanged and glucuronide conjugate forms; over 90% of an eslicarbazepine acetate dose is recovered in urine as unchanged eslicarbazepine (approximately two-thirds) or as glucuronide conjugates (approximately one-third).
The renal clearance of eslicarbazepine is substantially lower than the glomerular filtration rate in healthy individuals with normal renal function, suggesting that renal tubular reabsorption occurs. The elimination half-life of eslicarbazepine is 13-20 hours in patients with epilepsy. Hemodialysis partially clears eslicarbazepine from the systemic circulation in patients with end-stage renal disease.
USES: Eslicarbazepine is used to treat a certain type of seizure (focal seizures).
Generic name: eslicarbazepine acetate
Pronunciation: (ES-li-kar-BAZ-e-peen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
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Indications
The following indications are listed for Aptiom:
- Focal Epilepsy
Also known as: Cortical Epilepsy, Focal Seizures, Local Epilepsy, Partial Epilepsy, Partial Onset Seizures, Partial Seizures.
Dosing
Dosage of eslicarbazepine acetate is expressed in terms of the acetate salt.
Eslicarbazepine acetate tablets are administered orally once daily without regard to food. The tablets may be swallowed whole or crushed.
If therapy is to be discontinued, eslicarbazepine acetate should be withdrawn gradually to minimize the potential for increased seizure frequency and status epilepticus in patients with seizure disorders. (See Discontinuance of Therapy under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
Patients currently receiving or beginning therapy with eslicarbazepine acetate and/or any other anticonvulsant for any indication should be closely monitored for the emergence or worsening of depression, suicidal thoughts or behavior (suicidality), and/or any unusual changes in mood or behavior. (See Suicidality Risk under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
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Drug interactions
Eslicarbazepine is a moderate inhibitor of cytochrome P-450 (CYP) isoenzyme 2C19. In vivo studies suggest that eslicarbazepine can induce CYP3A4, leading to clinically relevant drug interactions with substrates of this isoenzyme. The drug does not appear to inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2D6, 2E1, or 3A4, nor to induce CYP1A2 or phase II hepatic enzymes involved in glucuronidation or sulfation. A mild activation of uridine diphosphate-glucuronosyltransferase (UGT) 1A1-mediated glucuronidation has been observed in vitro. Autoinduction of eslicarbazepine metabolism has not been observed.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Known hypersensitivity to eslicarbazepine acetate or oxcarbazepine. (See Sensitivity Reactions under Cautions: Warnings/Precautions.)
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in at least 4% of patients with partial-onset seizures receiving eslicarbazepine acetate in controlled clinical trials and at least 2% more frequently than placebo include dizziness, somnolence, nausea, vomiting, headache, diplopia, fatigue, vertigo, ataxia, blurred vision, and tremor.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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The manufacturer states that the safety and efficacy of eslicarbazepine acetate have not been established in pediatric patients younger than 18 years of age; the drug is not FDA-labeled for use in pediatric patients. However, the pharmacokinetics, efficacy, and tolerability of eslicarbazepine acetate have been evaluated in 29 pediatric patients (2-17 years of age) with refractory partial-onset seizures in an open study. The patients were divided into the following age groups: 2-6 years of age, 7-11 years of age, and 12-17 years of age. Peak plasma concentrations of eslicarbazepine were dose-dependent, were similar between age groups following identical dosage based on weight, and occurred within 0.5-3 hours in these pediatric patients. Area under the plasma concentration-time curve (AUC) was age-dependent due to faster plasma clearance of eslicarbazepine in the younger children compared with the older children. A dose-dependent decrease in relative seizure frequency was observed in the younger children (2-6 years of age) and adolescent (12-17 years of age) treatment groups, but not in the older children (7-11 years of age). Eslicarbazepine therapy was generally well tolerated in the pediatric patients in this study.
Category C. (See Users Guide.)
The North American Antiepileptic Drug (NAAED) Pregnancy Registry may be contacted at 888-233-2334 (for patients); NAAED registry information also is available on the website http://www.aedpregnancyregistry.org.
Eslicarbazepine acetate produced developmental toxicity, including teratogenicity, embryolethality, and fetal growth retardation, when administered orally to pregnant animals in clinically relevant dosages.
Eslicarbazepine is distributed into human milk. Because of the potential for serious adverse reactions to eslicarbazepine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Experience with eslicarbazepine acetate in patients 65 years of age and older is insufficient to establish efficacy in this population.
Patients 60 years of age and older appear to be at increased risk of adverse neurologic effects associated with eslicarbazepine acetate therapy (including dizziness, disturbances in gait or coordination, and visual changes) compared with younger adults. (See Neurologic Effects under Warnings/Precautions: Other Warnings and Precautions, in Cautions.)
In a study comparing single- and multiple-dose pharmacokinetics of eslicarbazepine acetate in geriatric individuals with a creatinine clearance greater than 60 mL/minute and younger healthy adults (18-40 years of age), the pharmacokinetic profile of the drug was similar between the 2 age groups. Although the pharmacokinetics of eslicarbazepine do not appear to be affected by age, the manufacturer states that dosage selection in geriatric patients should take into consideration the greater frequency of renal impairment and other concomitant medical conditions and medications in this population. Dosage adjustment is necessary in geriatric patients with a creatinine clearance of less than 50 mL/minute.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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