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Manufacturer:
GlaxoSmithKline Pharmaceuticals
Pharmacological Class:
Potassium channel opener.
Active Ingredient(s):
Ezogabine 50mg, 200mg, 300mg, 400mg; tablets.
Indication(s):
Adjunctive treatment of partial-onset seizures in patients ≥18 years old.
Pharmacology:
The mechanism by which ezogabine exerts its therapeutic effects has not been fully elucidated. In vitro studies indicate that ezogabine enhances transmembrane potassium currents mediated by the KCNQ (Kv 7.2 to 7.5) family of ion channels. By activating KCNQ channels, ezogabine is thought to stabilize the resting membrane potential and reduce brain excitability. In vitro studies suggest that ezogabine may also exert therapeutic effects through augmentation of GABA-mediated currents.
Clinical Trials:
The efficacy of Potiga as adjunctive therapy in partial-onset seizures was established in 3 multicenter, randomized, double-blind, placebo-controlled studies in 1,239 adult patients. The primary endpoint consisted of the percent change in seizure frequency from baseline in the double-blind treatment phase.
Patients enrolled in the studies had partial onset seizures w/ or w/o secondary generalization and were not adequately controlled with 1 to 3 concomitant AEDs, w/ or w/o concomitant vagus nerve stimulation. More than 75% of patients were taking 2 or more concomitant AEDs. During an 8-week baseline period, patients experienced at least 4 partial onset seizures per 28 days on average with no seizure-free period exceeding 3 to 4 weeks. Mean duration of epilepsy was 22 years. Across the 3 studies, the median baseline seizure frequency ranged from 8 to 12 seizures per month. The criteria for statistical significance was P<0.05.
Patients were randomized to the total daily maintenance dosages of 600mg/day, 900mg/day, or 1,200mg/day, each given in 3 equally divided doses. During the titration phase of all 3 studies, treatment was initiated at 300mg/day and increased in weekly increments of 150mg/day to the target maintenance dosage. A statistically significant effect was observed with Potiga at doses of 600mg/day (Study 1), at 900mg/day (Studies 1 and 3), and at 1,200mg/day (Studies 2 and 3) in the median percent reduction in 28-day seizure frequency (baseline to double-blind phase) as compared with placebo across all 3 studies.
Legal Classification:
CV
Adults:
Swallow whole. Give in 3 equally divided doses daily. ≥18 years: initially 300mg/day for 1 week; titrate at weekly intervals by no more than 150mg/day up to a maintenance dose of 600–1200mg/day. Elderly (>65 years) or hepatic impairment (Child-Pugh 7–9): initially 150mg/day; max 750mg/day. Renal impairment (CrCl <50mL or ESRD on dialysis) or hepatic impairment (Child-Pugh >9): initially 150mg/day; max 600mg/day. See literature.
Children:
Children: <18 years: not established.
Warnings/Precautions:
Increased risk of urinary retention; monitor closely in patients with BPH, cognitively impaired, or concomitant medications that may affect voiding (eg, anticholinergics). Monitor for neuropsychiatric symptoms (eg, confusional state, psychosis, hallucinations), dizziness, somnolence. Monitor QT interval in patients with known prolonged QT interval, CHF, ventricular hypertrophy, hypokalemia, or hypomagnesemia. Monitor for emergence or worsening of depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior. Avoid abrupt cessation; withdraw gradually over at least 3 weeks. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interaction(s):
Caution with drugs known to increase the QT interval. Plasma levels reduced by concomitant phenytoin or carbamazepine; consider increasing ezogabine dose. May potentiate digoxin; monitor. Increased exposure with alcohol; caution. May interfere in clinical lab assays of serum and urine bilirubin.
Adverse Reaction(s):
Dizziness, somnolence, fatigue, confusional state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, memory impairment, asthenia, blurred vision, gait disturbance, aphasia, dysarthria, balance disorder.
How Supplied:
Tabs—90
Potiga(ezogabine) 获批用于成人癫痫辅助用药
Potiga是首个神经元钾通道开放制剂。美国食品和药品监督管理局批准抗惊厥药Potiga(ezogabine)作为癫痫患者局部癫痫的辅助用药，其活性成分于今年3月份获得欧洲药品管理局的批准，将于年底进入美国市场。癫痫患者有复发癫痫倾向，由突发脑电活动诱发，导致大脑超负荷。脑细胞间的信息传播系统出现短暂紊乱。局部癫痫仅影响大脑部分区域，但可传导至大脑其他部位。
制造商：
葛兰素史克制药
类药物：
钾通道开放。
活性成分（S）：
ezogabine 50毫克，200毫克，300毫克，400毫克;片。
指示（S）：
在≥18岁患者的部分发作的辅助治疗。
药理作用：
通过ezogabine发挥其治疗作用的机制尚未完全阐明。体外研究表明，ezogabine提高KCNQ（KV 7.2至7.5）离子通道家族介导的跨膜钾电流。通过激活KCNQ渠道，ezogabine被认为是稳定的静息膜电位，降低大脑的兴奋。体外研究表明，ezogabine也可能通过增强GABA介导电流的治疗效果发挥。
临床试验：
在3个多中心，随机，双盲，安慰剂对照研究在1239成人患者局部发作的辅助治疗功效的Potiga成立。主要终点包括在双盲治疗阶段的基线发作频率的百分比变化。
参加研究的患者有部分癫痫发作W / W / O二级概括和1至3伴随抗癫痫药物，W / W / O伴随刺激迷走神经没有得到充分控制。超过75％的患者服用2个或更多伴随抗癫痫药物。在为期8周的基线期，患者没有发作的时间超过3至4周，平均每28天至少有4个部分发作。癫痫的平均时间为22年。横跨3项研究中，中位数基线发作频率从每月8日至12缉获。统计学意义的标准是P <0.05;
患者被随机600mg/day，900mg/day，或1200毫克/天，每3剂量相等的总日常维护剂量。在滴定所有3个研究阶段，治疗开始300mg/day增长目标维持剂量150mg剂量每周递增。 600mg/day剂量（研究1）与Potiga观察统计学显着的效果，在900mg/day（研究1和3），并在1200毫克/天（研究2和3）中位数在28％减少 - 一天发作频率（基线双盲阶段）相比，在所有3项研究的安慰剂。
法律分类：
简历
成人：
吞下。每天给3分同样的剂量。 ≥18岁：最初300mg/day 1周，每周一班由不超过150mg剂量维持剂量最多的600-1200mg/day滴定。老年人（> 65岁）或肝功能不全（Child-Pugh分级7-9）：最初150mg剂量，最大750mg/day。肾功能不全（肌酐清除率<50ml或透析的ESRD）或肝功能不全（Child-Pugh分级> 9）：最初150mg剂量，最大600mg/day。见文献。
儿童：
儿童：<18岁：不成立的。
警告/注意事项：
尿潴留的风险增加; BPH患者密切监视，认知障碍，或合并用药，可能会影响排尿（如抗胆碱能）。监测神经精神症状（例如，混乱状态，精神错乱，幻觉），头晕，嗜睡。显示器QT间期延长QT间隔，瑞士法郎，心室肥大，低血钾，或低镁血症患者。监测抑郁症的出现或恶化，自杀的念头/行为，和/或情绪或行为的不寻常的变化。避免突然停止;逐步撤回了至少3个星期。怀孕（部件）。哺乳母亲：不推荐。
互动（补）：
注意与已知会增加QT间隔的药物。伴随苯妥英或卡马西平降低血浆水平;考虑增加ezogabine剂量。会增强地高辛;监控。增加曝光用酒精;谨慎。在临床实验室检测血清和尿胆红素可能会干扰。
不良反应（S）：
头晕，嗜睡，疲劳，精神错乱状态，眩晕，震颤，协调异常，复视，注意障碍，记忆障碍，乏力，视力模糊，步态障碍，失语，构音障碍，平衡障碍。
如何提供：
标签-90
最后更新：
2012年6月25日
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