Eslicarbazepine acetate

296.324

296.32

1592732-453-0

BEA68ZVB2K

DTXSID90178308

N03AF04

72.6

2

white solid

1.3±0.1 g/cm3

186-187 °C

427.4°C at 760 mmHg

212.3±31.5 °C

1.655

Water solubility of eslicarbazepine acetate is low at less than 1 mg/mL including at different pH values. Its main metabolite eslicarbazepine has a greater water solubility of 4.2 mg/mL.

2-8°C

NONH for all modes of transport

3

36/37/38

26-36

Xi

P261-P305 + P351 + P338

H315-H319-H335

|Warning|H315 (98.91%): Causes skin irritation [Warning Skin corrosion/irritation]|P261, P264, P271, P280, P302+P352, P304+P340, P305+P351+P338, P312, P321, P332+P313, P337+P313, P362, P403+P233, P405, and P501|Aggregated GHS information provided by 92 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

There are no adequate and well-controlled studies of the use of eslicarbazepine acetate in pregnant women. In studies conducted in pregnant mice, rats, and rabbits, eslicarbazepine acetate did show developmental toxicities, including teratogenicity, embryolethality, and fetal growth retardation, at clinically relevant doses. Drug-induced liver injury ranging from mild to moderate elevations in transaminases (>3 times the upper limit of normal) to rare cases with concomitant elevations of total bilirubin (>2 times the upper limit of normal) have been reported with the use of eslicarbazepine. Overdose with eslicarbazepine acetate appears similar to its known adverse reactions and includes symptoms of hyponatremia, dizziness, nausea, vomiting, somnolence, euphoria, oral paraesthesias, ataxia, and diplopia. There is no specific antidote for eslicarbazepine acetate overdose and it should be treated primarily with supportive measures. If required, the drug may be removed by gastric lavage, partially by hemodialysis or inactivated with activated charcoal.

Eslicarbazepine is bound to plasma proteins at a relatively low rate of <40%, independent of concentration. In vitro studies have shown that plasma protein binding is not relevantly affected by the presence of other medications such as warfarin, diazepam, digoxin, phenytoin or tolbutamide. Similarly, the binding of these medications was not significantly affected by the presence of eslicarbazepine.

Eslicarbazepine acetate is indicated as adjunctive therapy in the treatment of partial-onset seizures that are not adequately controlled with conventional therapy in epileptic patients.|FDA Label|Zebinix is indicated as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.|Exalief is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary generalisation.|Treatment of epilepsy with partial-onset seizures

Eslicarbazepine acetate is associated with a dose- and concentration-dependant increase in heart rate and prolongation of PR interval.

Drugs used to prevent SEIZURES or reduce their severity. (See all compounds classified as Anticonvulsants.)|A class of drugs that inhibit the activation of VOLTAGE-GATED SODIUM CHANNELS. (See all compounds classified as Voltage-Gated Sodium Channel Blockers.)

Eslicarbazepine active metabolite has a high bioavailability and reaches peak serum concentration 1-4 hours after a given dose. Eslicarbazepine acetate absorption is not affected by food.|Eslicarbazepine acetate and its metabolites are eliminated primarily via renal excretion. Eslicarbazepine active metabolite is excreted two-thirds in the unchanged form and one-third as a glucuronide conjugate. This accounts for around 90% of total metabolites excreted, with the remaining 10% being minor metabolites. Renal tubular reabsorption is expected to occur with eslicarbazepine.|The apparent volume of distribution of eslicarbazepine is 61.3 L for a body weight of 70 kg based on population PK analysis.|Renal clearance of eslicarbazepine was found to be approximately 20 mL/min in healthy subjects with normal renal function.

Eslicarbazepine acetate is rapidly and extensively metabolized to its major active metabolite, eslicarbazepine, via hydrolytic first-pass metabolism. Eslicarbazepine corresponds to about 92% of systemic exposure. Minor active metabolites (R)-licarbazepine and oxcarbazepine consist of <5% of systemic exposure. Active metabolites are then metabolized to inactive glucuronides that correspond to about 3% of systemic exposure. Eslicarbazepine had a moderate inhibitory effect on CYP2C19 and a mild activation of UGT1A1-mediated glucuronidation when studied in human hepatic microsomes. It has been shown to induce CYP3A4 enzymes in vivo.

The apparent plasma half-life of eslicarbazepine is 10-20 hours in healthy subjects and 13-20 hours in epilepsy patients. Steady-state plasma concentrations are attained after 4 to 5 days of once daily dosing.

Eslicarbazepine acetate is converted to the active metabolite eslicarbazepine which carries out its anticonvulsant activity. The exact mechanism of action is unknown, but it is thought to involve the inhibition of voltage-gated sodium channels. In in vitro electrophysiological studies, eslicarbazepine was shown to inhibit repeated neuronal firing by stabilizing the inactivated state of voltage-gated sodium channels and preventing their return to the activated state. In vitro studies also showed eslicarbazepine inhibiting T-type calcium channels, which likely also has a role in anticonvulsant activity.

10-acetoxy-10,11-dihydro-5H-dibenz(b,f)azepine-5-carboxamide

Human drugs -> Zebinix -> EMA Drug Category|Antiepileptics -> Human pharmacotherapeutic group|Human drugs -> Exalief -> EMA Drug Category|Human Drugs -> EU pediatric investigation plans|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients