Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy
Received 7 January 2018
Accepted for publication 11 February 2018
Published 8 March 2018 Volume 2018:13 Pages 21—31
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Garry Walsh
Simona Lattanzi,1 Francesco Brigo,2,3 Claudia Cagnetti,1 Alberto Verrotti,4 Gaetano Zaccara,5 Mauro Silvestrini1
1Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca, Ancona, Italy; 2Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Italy; 3Division of Neurology, “Franz Tappeiner” Hospital, Merano BZ, Italy; 4Department of Pediatrics, University of L’Aquila, L’Aquila, Italy; 5Unit of Neurology, Department of Medicine, Usl Centro Toscana Health Authority, Firenze, Italy
Introduction: Up to 30% of the patients diagnosed with epilepsy will continue suffering from seizures despite treatment with antiepileptic drugs, either in monotherapy or polytherapy. Hence, there remains the need to develop new effective and well-tolerated therapies.
Aim: The objective of this article was to review the evidence for the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive treatment in adult patients with focal onset seizures.
Evidence review: ESL is the newest, third-generation, single enantiomer member of the dibenzazepine family. Following oral administration, ESL is rapidly and extensively metabolized by hepatic first-pass hydrolysis to the active metabolite eslicarbazepine, which has linear, dose-proportional pharmacokinetics and low potential for drug-drug interactions. Eslicarbazepine works as a competitive blocker of the voltage gated sodium channels; unlike carbamazepine (CBZ) and oxcarbazepine (OXC), it has a lower affinity for the resting state of the channels, and reduces their availability by selectively enhancing slow inactivation. Efficacy and safety of ESL have been assessed in four randomized, Phase III clinical trials: the median relative reduction in standardized seizure frequency was 33.4% and 37.8% in the ESL 800 and 1,200 mg daily dose groups, and the responder rates were 33.8% and 43.1%, respectively. The incidence of treatment-emergent adverse events (TEAEs) increased with raising the dosage (ESL 400 mg: 63.8%, ESL 800 mg: 67.0%, ESL 1,200 mg: 73.1%). The TEAEs were generally mild to moderate in intensity, and the most common were dizziness, somnolence, headache and nausea. Open-label studies confirmed the findings from the pivotal trials and demonstrated sustained therapeutic effect of ESL over time and improvement of tolerability profile in patients switching from OXC/CBZ. No unexpected safety signals emerged over >5 years of follow-up.
Conclusion: Once-daily adjunctive ESL at the doses of 800 and 1,200 mg was effective to reduce the seizure frequency and was fairly well tolerated in adults with focal onset epilepsy. Starting treatment at 400 mg/day, followed by 400 mg increments every 7–14 days, could provide the optimal balance of efficacy and tolerability.
Keywords: eslicarbazepine acetate, epilepsy, focal seizures, review
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