Clinical utility of eslicarbazepine: current evidence
Gaetano Zaccara,1 Fabio Giovannelli,1,2 Massimo Cincotta,1 Alessia Carelli,3 Alberto Verrotti31Department of Medicine, Unit of Neurology, Florence Health Authority, Florence, Italy; 2Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of F...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2015-02-01
|
| Series: | Drug Design, Development and Therapy |
| Online Access: | http://www.dovepress.com/clinical-utility-of-eslicarbazepine-current-evidence-peer-reviewed-article-DDDT |
| _version_ | 1818859261419061248 |
|---|---|
| author | Zaccara G Giovannelli F Cincotta M Carelli A Verrotti A |
| author_facet | Zaccara G Giovannelli F Cincotta M Carelli A Verrotti A |
| author_sort | Zaccara G |
| collection | DOAJ |
| description | Gaetano Zaccara,1 Fabio Giovannelli,1,2 Massimo Cincotta,1 Alessia Carelli,3 Alberto Verrotti31Department of Medicine, Unit of Neurology, Florence Health Authority, Florence, Italy; 2Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy; 3Department of Pediatrics, University of Perugia, Perugia, ItalyAbstract: 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.Keywords: antiepileptic drugs, epilepsy, eslicarbazepine acetate, pharmacoresistant epilepsy, oxcarbazepine, carbamazepine |
| first_indexed | 2024-12-19T09:09:22Z |
| format | Article |
| id | doaj.art-e8ecd41e8d7f4aa68e7e1b11acbd9e67 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-19T09:09:22Z |
| publishDate | 2015-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-e8ecd41e8d7f4aa68e7e1b11acbd9e672022-12-21T20:28:14ZengDove Medical PressDrug Design, Development and Therapy1177-88812015-02-012015default78178920375Clinical utility of eslicarbazepine: current evidenceZaccara GGiovannelli FCincotta MCarelli AVerrotti AGaetano Zaccara,1 Fabio Giovannelli,1,2 Massimo Cincotta,1 Alessia Carelli,3 Alberto Verrotti31Department of Medicine, Unit of Neurology, Florence Health Authority, Florence, Italy; 2Department of Neuroscience, Psychology, Pharmacology and Child Health (NEUROFARBA), University of Florence, Florence, Italy; 3Department of Pediatrics, University of Perugia, Perugia, ItalyAbstract: 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.Keywords: antiepileptic drugs, epilepsy, eslicarbazepine acetate, pharmacoresistant epilepsy, oxcarbazepine, carbamazepinehttp://www.dovepress.com/clinical-utility-of-eslicarbazepine-current-evidence-peer-reviewed-article-DDDT |
| spellingShingle | Zaccara G Giovannelli F Cincotta M Carelli A Verrotti A Clinical utility of eslicarbazepine: current evidence Drug Design, Development and Therapy |
| title | Clinical utility of eslicarbazepine: current evidence |
| title_full | Clinical utility of eslicarbazepine: current evidence |
| title_fullStr | Clinical utility of eslicarbazepine: current evidence |
| title_full_unstemmed | Clinical utility of eslicarbazepine: current evidence |
| title_short | Clinical utility of eslicarbazepine: current evidence |
| title_sort | clinical utility of eslicarbazepine current evidence |
| url | http://www.dovepress.com/clinical-utility-of-eslicarbazepine-current-evidence-peer-reviewed-article-DDDT |
| work_keys_str_mv | AT zaccarag clinicalutilityofeslicarbazepinecurrentevidence AT giovannellif clinicalutilityofeslicarbazepinecurrentevidence AT cincottam clinicalutilityofeslicarbazepinecurrentevidence AT carellia clinicalutilityofeslicarbazepinecurrentevidence AT verrottia clinicalutilityofeslicarbazepinecurrentevidence |