Department of Neurology, Johns Hopkins Hospital, Baltimore, Maryland 21287-7247, USA.
Epilepsia. 2010 Jun;51(6):951-7. doi: 10.1111/j.1528-1167.2009.02463.x. Epub 2009 Dec 22.
Lacosamide is a new antiepileptic drug effective for adjunctive treatment of partial-onset seizures. We evaluated the safety and tolerability of an intravenous (i.v.) formulation of lacosamide (200-800 mg/day) infused over 10, 15, and 30 min as short-term replacement for oral lacosamide in patients with partial-onset seizures.
This multicenter, open-label, inpatient trial enrolled 160 patients from ongoing open-label, long-term trials who were taking stable doses of oral lacosamide and up to three concomitant antiepileptic drugs (AEDs). Serial cohorts of patients were converted from oral lacosamide treatment to the same intravenous doses infused over progressively shorter infusion durations: 30, 15, and 10 min for 2-5 days. A data monitoring committee (DMC) reviewed safety data for each cohort. The safety of intravenous lacosamide was assessed from adverse events (AEs), laboratory variables, electrocardiography findings, and physical/neurologic examinations.
A total of 160 patients received lacosamide 200-800 mg/day, i.v., for 2-5 days, of which 69% received 400-800 mg/day doses. The most common AEs (reported by <or=10% of patients) were headache, dizziness, and somnolence. There was no increase in frequency or severity of AEs with shorter durations of infusion or increased days of exposure. AEs were similar, but more frequent, with higher doses (>or=400 mg/day). Injection-site events were rare and did not appear to be linked to infusion doses or rates. Lacosamide plasma concentrations were linearly related to dose across the cohorts.
This comprehensive evaluation supports the safety of an intravenous lacosamide infusion duration as short as 15 min for short-term (2-5 days) replacement for patients temporarily unable to take oral lacosamide.
拉科酰胺是一种新的抗癫痫药物，对部分发作性癫痫的辅助治疗有效。我们评估了静脉（IV）制剂拉科酰胺（200-800mg/天）输注 10、15 和 30 分钟作为短期替代口服拉科酰胺的安全性和耐受性，用于部分发作性癫痫患者。
这项多中心、开放性、住院患者试验纳入了正在进行的开放性、长期试验中服用稳定剂量口服拉科酰胺和最多三种同时使用的抗癫痫药物（AED）的 160 例患者。连续队列的患者从口服拉科酰胺治疗转换为相同的静脉剂量，输注时间逐渐缩短：30、15 和 10 分钟，持续 2-5 天。一个数据监测委员会（DMC）审查了每个队列的安全性数据。静脉拉科酰胺的安全性根据不良事件（AE）、实验室变量、心电图发现和身体/神经病学检查来评估。
共有 160 例患者接受了拉科酰胺 200-800mg/天，IV，治疗 2-5 天，其中 69%接受了 400-800mg/天的剂量。最常见的 AE（<或=10%的患者报告）为头痛、头晕和嗜睡。随着输注时间的缩短或暴露天数的增加，AE 的频率或严重程度没有增加。AE 相似，但更频繁，剂量更高（>或=400mg/天）。注射部位事件罕见，似乎与输注剂量或速率无关。拉科酰胺的血浆浓度与剂量呈线性相关。
这项全面的评估支持静脉拉科酰胺输注时间最短可达 15 分钟，用于暂时不能服用口服拉科酰胺的患者短期（2-5 天）替代治疗的安全性。
