近期；FDA批准了每日一次的奥卡西平缓释制剂(Oxtellar XR，制药公司Supernus)用于成人和6至17岁的儿童部分性发作的辅助治疗

药理类别：
二苯并氮杂。

活性成分（S）：
奥卡西平150毫克，300毫克，600毫克;缓释片。

公司
Supernus制药
指示（S）：
在治疗成人和6-17岁儿童部分性癫痫发作的辅助治疗。

药理作用：
奥卡西平的10 - 羟基代谢物（MHD）发挥其抗癫痫作用的确切机制是未知的，但是，在体外研究表明，它们产生的电压敏感的钠通道的阻断，产生稳定神经hyperexcited膜，重复神经元的抑制射击，并缩减突触冲动的传播。此外，增加的钾电导，高电压激活钙通道的调制可能有助于奥卡西平的抗惊厥作用。

临床试验：
的安全性和有效性进行了评估，的Oxtellar XR一项多中心，随机，双盲，安慰剂对照，三臂平行组研究（研究1）在成人难治性部分性癫痫患者年龄在18-65岁组（n = 366 ）。这项研究包括8周的基线期，治疗期间（4周的调整期，其次是一项为期12周的维护阶段）。主要终点是从基线发作频率每28天的中位数百分比的变化，治疗期间相对基准期。用于统计显着性为p <0.05的标准。患者被随机分为三个治疗组之一，并给予XR 1.2g/day Oxtellar组（n = 122），Oxtellar：XR 2.4g/day（N = 123），或安慰剂组（n = 121）。主要疗效结果表现出的中位数百分比变化发作频率为-38.2％（P <0.078）和-42.9％（P <0.003），XR 1.2g/day Oxtellar和2.4g/day治疗组，分别与 - 安慰剂组的28.7％。虽然1.2g/day与安慰剂对比没有达到统计学意义，浓度响应分析表明，剂量1.2g/day是一种有效的剂量。

法律分类：
接收

成人：
空腹服用。整片吞服。 > 17yrs：最初600毫克，每日一次持续1周，则可能会增加600mg/day递增每周间隔;通常范围1.2g-2.4g/day。伴随抗癫痫药：考虑启动900毫克，每日一次。严重肾功能不全（肌酐清除率<30ml/min者）：最初300mg/day;可能会增加每周一班300-450mg/day增量的。终末期肾病透析：使用奥卡西平立即释放。老人：最初300毫克或450毫克，每日一次;，可能每周间隔增加300-450mg/day增量。奥卡西平立即释放的转换可能需要更高的剂量。

儿童：
<6岁：不推荐。 6-17yrs：最初8-10mg/kg，每日一次;最大600mg/day在第一周，然后可以增加8-10mg/kg/day增量每周一班，平常最大600mg/day。目标维持剂量（获得超过2-3周）：2029千克：900mg/day; 29.​​139千克：1.2g/day;>39公斤：1.8g/day。

警告/注意事项：
低钠血症的风险监控，如果出现症状/体征。严重肝功能不全：不推荐。卡马西平过敏。自杀行为和意念;显示器。停止如果发生多器官超敏反应，使用替代治疗。避免突然停药。老年人。怀孕（Cat.C）：癫痫发作的风险;监测期间和产后。哺乳母亲：不推荐。

互动（补）
苯妥英钠，卡马西平，苯巴比妥，丙戊酸拮抗，监测和调整剂量。激素避孕药（左炔诺孕酮炔雌醇），其他口头或植入避孕药的有效性可能会降低，使用额外的非激素类的形式。注意与其他药物降低血清钠。可能会影响甲状腺（T4）测试。

不良反应（S）
头晕，嗜睡，头痛，平衡障碍，震颤，呕吐，复视，乏力，疲劳，低钠血症，严重的皮肤反应（例如，史蒂文斯 - 约翰逊综合征和中毒性表皮坏死松解症）;罕见：过敏反应，血管神经性水肿，血液系统的反应;停止，如果发生。

如何提供：
标签-100

最后更新：
2013年2月14日

http://www.drugs.com/pro/oxtellar-xr.html

FDA批准奥卡西平缓释制剂用于癫痫的辅助治疗
美国食品和药品管理局(FDA)已经批准了一项新的每日一次的奥卡西平缓释制剂(Oxtellar XR，制药公司Supernus)用于成人和6至17岁的儿童部分性发作的辅助治疗。
该剂型前身是SPN-804，建议剂量为成人每天1200至2400年毫克，年龄在6至17岁的儿童根据体重每天900至1800毫克。该产品将提供150毫克，300毫克，600毫克缓释片。
该公司指出，他们将在2013年第一季度推出新的治疗方法。
新配方的批准基于一项多中心，随机，双盲，3组年龄在18岁至65岁的成人难治性部分性癫痫的研究结果。一共有369例患者随机分配，其中366个患者意图治疗。
与安慰剂相比，2400毫克/天剂量的SPN-804显著增加反应率(P= 0.018)，并且增加治疗期间(P= 0.013)和维持期间(P= 0.008)癫痫不发作时间。
服用SPN-804 2400毫克/天，1200毫克/天，与安慰剂相比，不良反应的发生率分别为69.1%，56.6%和54.5%；严重不良事件发生分别为9.8%，6.6%和6.6%。SPN-804的最常见的不良反应是头晕，嗜睡，头痛，恶心，复视，呕吐。治疗组没有死亡病例的报道。

OXTELLAR XR

Pharmacological Class:
Dibenzazepine.

Active Ingredient(s):
Oxcarbazepine 150mg, 300mg, 600mg; extended-release tablets.

Company
Supernus Pharmaceuticals
Indication(s):
Adjunctive therapy in the treatment of partial seizures in adults and in children 6–17 years of age.

Pharmacology:
The precise mechanism by which oxcarbazepine and 10-monohydroxy metabolite (MHD) exert their antiseizure effect is unknown; however, in vitro studies indicate that they produce blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neural membranes, inhibition of repetitive neuronal firing, and diminution of propagation of synaptic impulses. In addition, increased potassium conductance and modulation of high-voltage activated calcium channels may contribute to the anticonvulsant effects of oxcarbazepine.

Clinical Trials:
The safety and efficacy of Oxtellar XR was evaluated in a multicenter, randomized, double-blind, placebo-controlled, three-arm parallel-group study (Study 1) in adult patients with refractory partial epilepsy aged 18–65 years (n=366). The study included an 8-week baseline period, followed by a treatment period (4-week titration phase followed by a 12-week maintenance phase). The primary endpoint was median percentage change from baseline in seizure frequency per 28 days during treatment period relative to the baseline period. The criterion for statistical significance was p<0.05. Patients were randomized to one of three treatment groups and were given Oxtellar XR 1.2g/day (n=122), Oxtellar XR 2.4g/day (n=123), or placebo (n=121). The primary efficacy results demonstrated a median percent change in seizure frequency of -38.2% (p<0.078) and -42.9% (p<0.003) in the Oxtellar XR 1.2g/day and 2.4g/day treatment groups, respectively vs. -28.7% in the placebo group. Although the 1.2g/day vs. placebo contrast did not reach statistical significance, concentration-response analyses reveal that the 1.2g/day dose is an effective dose.

Legal Classification:
Rx

Adults:
Take on empty stomach. Swallow whole. >17yrs: Initially 600mg once daily for 1 week, then may increase by 600mg/day increments at weekly intervals; usual range 1.2g–2.4g/day. Concomitant antiepileptics: consider initiating at 900mg once daily. Severe renal impairment (CrCl <30mL/min): initially 300mg/day; may increase by 300–450mg/day increments at weekly intervals. ESRD on dialysis: use oxcarbazepine immediate-release. Elderly: initially 300mg or 450mg once daily; may increase by 300–450mg/day increments at weekly intervals. Conversion from oxcarbazepine immediate-release: may need higher doses.

Children:
<6yrs: not recommended. 6–17yrs: initially 8–10mg/kg once daily; max 600mg/day in the 1st week, then may increase by 8–10mg/kg/day increments at weekly intervals; usual max 600mg/day. Target maintenance doses (attain over 2–3 weeks): 20–29kg: 900mg/day; 29.1–39kg: 1.2g/day; >39kg: 1.8g/day.

Warnings/Precautions:
Risk of hyponatremia; monitor if signs/symptoms occur. Severe hepatic impairment: not recommended. Carbamazepine hypersensitivity. Suicidal behavior and ideation; monitor. Discontinue if multi-organ hypersensitivity occurs; use alternative treatment. Avoid abrupt withdrawal. Elderly. Pregnancy (Cat.C): risk of seizures; monitor during and postpartum. Nursing mothers: not recommended.

Interaction(s)
Antagonized by phenytoin, carbamazepine, phenobarbital, valproic acid; monitor and adjust dose. May decrease effectiveness of hormonal contraceptives (ethinyl estradiol, levonorgestrel), other oral or implant contraceptives; use additional non-hormonal forms. Caution with other drugs known to decrease serum sodium. May affect thyroid (T4) tests.

Adverse Reaction(s)
Dizziness, somnolence, headache, balance disorder, tremor, vomiting, diplopia, asthenia, fatigue; hyponatremia, serious skin reactions (eg, Stevens-Johnson syndrome and toxic epidermal necrolysis); rare: anaphylactic reactions, angioedema, hematological reactions; discontinue if occurs.

How Supplied:
Tabs—100

LAST UPDATED:
2/14/2013