Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy.
Eslicarbazepine acetate in the treatment of adults with partial-onset epilepsy: an evidence-based review of efficacy, safety and place in therapy.
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DOI：
10.2147/ce.s142858
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Silvestrini M
中科院分区：
文献类型：
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作者：
Lattanzi S;Brigo F;Cagnetti C;Verrotti A;Zaccara G;Silvestrini M
高达30%的诊断为癫痫的患者将继续遭受癫痫发作，尽管与抗癫痫药物治疗，无论是在单药治疗或多药治疗。因此，仍然需要开发新的有效且耐受性良好的疗法。本文的目的是审查醋酸艾司利卡西平（ESL）作为局灶性癫痫发作成人患者连续治疗的有效性和安全性的证据。ESL是二苯并氮杂卓家族中最新的第三代单一对映体成员。口服给药后，ESL通过肝脏首过水解快速广泛代谢为活性代谢物艾司利卡西平，其具有线性、剂量比例药代动力学和低药物相互作用可能性。艾司利卡西平作为电压门控钠通道的竞争性阻断剂发挥作用;与卡马西平（CBZ）和奥卡西平（OXC）不同，它对通道的静息状态具有较低的亲和力，并通过选择性增强缓慢失活来降低其可用性。在四项随机、III期临床试验中评估了ESL的疗效和安全性：ESL 800和1，200 mg每日剂量组标准化癫痫发作频率的中位相对降低分别为33.4%和37.8%，应答率分别为33.8%和43.1%。治疗后出现的不良事件（TEAE）的发生率随剂量增加而增加（ESL 400 mg：63.8%，ESL 800 mg：67.0%，ESL 1，200 mg：73.1%）。TEAE的严重程度通常为轻度至中度，最常见的是头晕、嗜睡、头痛和恶心。开放标签研究证实了关键试验的结果，并证明了ESL随时间的持续治疗效果，以及从OXC/CBZ转换的患者的耐受性特征改善。在>5年的随访中，未出现意外的安全性信号。800和1，200 mg剂量的每日一次连续ESL可有效降低癫痫发作频率，并且在局灶性癫痫发作成人中耐受性良好。以400 mg/天开始治疗，然后每7-14天增加400 mg，可以提供疗效和耐受性的最佳平衡。
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. 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. 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. 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.