Clinical utility of eslicarbazepine: current evidence

• Published in: Drug design, development and therapy Vol. 9; no. default; pp. 781 - 789
• Main Authors: Zaccara, Gaetano, Giovannelli, Fabio, Cincotta, Massimo, Carelli, Alessia, Verrotti, Alberto
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2015; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Acetic acid; Affinity; Animals; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Anticonvulsants - therapeutic use; Antiepileptic agents; antiepileptic drugs; Carbamazepine; Children; Clinical trials; Convulsions & seizures; Deactivation; Dibenzazepines - administration & dosage; Dibenzazepines - adverse effects; Dibenzazepines - therapeutic use; Dosage and administration; Drug dosages; Drug metabolism; Drug resistance; Drug therapy; Epilepsy; Eslicarbazepine acetate; Esterases; Headache; Humans; Inactivation; Medical research; Mental disorders; Nausea; Neurological diseases; Oral administration; Oxcarbazepine; Patients; Pharmacology; pharmacoresistant epilepsy; Physiological aspects; Physiology; Plasma proteins; Review; Seizures; Seizures - diagnosis; Seizures - drug therapy; Sodium; Sodium channels (voltage-gated); Trade names; Vertigo; Vomiting; United States > US; Italy; epilepsy; antiepileptic drugs; eslicarbazepine acetate; oxcarbazepine; pharmacoresistant epilepsy; carbamazepine
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S57409

Eslicarbazepine acetate (ESL) is a new antiepileptic drug whose mechanism of action is blockade of the voltage-gated sodium channel (VGSC). However, in respect to carbamazepine and oxcarbazepine, the active ESL metabolite (eslicarbazepine) affects slow inactivation of VGSC and has a similar affinity for the inactivated state and a lower affinity for the resting state of the channel. This new antiepileptic drug has been recently approved in Europe (trade name Zebinix) and in the United States (trade name Stedesa) for adjunctive treatment in adult subjects with partial-onset seizures, with or without secondary generalization. Following oral administration, ESL is rapidly and extensively metabolized by hepatic esterases to eslicarbazepine. This active metabolite has a linear pharmacokinetic profile, a low binding to plasma proteins (<40%), and a half-life of 20-24 hours and is mainly excreted by kidneys in an unchanged form or as glucuronide conjugates. ESL is administered once a day and has a low potential for drug-drug interactions. Efficacy and safety of this drug in patients with focal seizures have been assessed in four randomized clinical trials, and responder rates (percentage of patients with a ≥50% improvement of their seizures) ranged between 17% and 43%. Adverse events were usually mild to moderate, and the most common were dizziness, somnolence, diplopia, abnormal coordination, blurred vision, vertigo, headache, fatigue, nausea, and vomiting. ESL may be considered an interesting alternative to current antiepileptic drugs for the treatment of drug-resistant focal epilepsies. Additionally, it is under investigation in children with focal epilepsies, in patients with newly diagnosed focal epilepsies, and also in other neurological and psychiatric disorders.