Striano Pasquale, McMurray Rob, Santamarina Estevo, Falip Mercè
Paediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, G. Gaslini Institute, Genova, Italy.
Eisai Europe Ltd, Hatfield, UK.
Epileptic Disord. 2018 Feb 1;20(1):13-29. doi: 10.1684/epd.2017.0950.
Rufinamide was granted orphan drug status in 2004 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients aged ≥4 years, and was subsequently approved for this indication in several countries, including Europe and the United States. Structurally unrelated to other antiepileptic drugs, rufinamide is thought to act primarily by prolonging the inactivation phase of voltage-gated sodium channels. Rufinamide was approved on the basis of an international, randomised, placebo-controlled Phase III trial, conducted in 138 patients with Lennox-Gastaut syndrome, which demonstrated its favourable tolerability profile and efficacy in significantly reducing the frequency of drop attacks and total seizures, compared with placebo. The effectiveness and safety/tolerability of rufinamide in treating seizures associated with Lennox-Gastaut syndrome have subsequently been confirmed in several other clinical trials and long-term extension studies. These findings are supported by 'real-world' data from a series of clinical practice studies conducted in Europe, the United States, and Korea. Rufinamide has been shown to be effective and generally well tolerated in children as young as one year and in adults. It is particularly effective as treatment for drop attacks and generalised tonic-clonic seizures, and it has been suggested that it might be preferred over other antiepileptic drugs as a second-line treatment for Lennox-Gastaut syndrome when drop attacks are frequent. The most common side effects of rufinamide treatment include somnolence, headache, dizziness, nausea, vomiting, and fatigue. No new or unexpected safety signals have emerged following long-term treatment with rufinamide, either in clinical trials or in clinical practice.
卢非酰胺于2004年被授予孤儿药地位，用于辅助治疗≥4岁 Lennox-Gastaut 综合征患者的癫痫发作，随后在包括欧洲和美国在内的多个国家被批准用于该适应症。卢非酰胺在结构上与其他抗癫痫药物无关，其作用机制主要被认为是延长电压门控钠通道的失活期。卢非酰胺基于一项国际随机安慰剂对照III期试验获批，该试验纳入了138例Lennox-Gastaut综合征患者，结果表明与安慰剂相比，其耐受性良好且能显著降低跌倒发作和癫痫总发作频率。随后在其他多项临床试验和长期扩展研究中证实了卢非酰胺治疗Lennox-Gastaut综合征相关癫痫发作的有效性和安全性/耐受性。欧洲、美国和韩国开展的一系列临床实践研究的“真实世界”数据支持了这些发现。卢非酰胺已被证明在1岁幼儿和成人中有效且总体耐受性良好。它对跌倒发作和全身强直阵挛性发作的治疗特别有效，有人认为当跌倒发作频繁时，作为Lennox-Gastaut综合征的二线治疗药物，它可能比其他抗癫痫药物更受青睐。卢非酰胺治疗最常见的副作用包括嗜睡、头痛、头晕、恶心、呕吐和疲劳。在临床试验或临床实践中，长期使用卢非酰胺后未出现新的或意外的安全信号。
