近日，美国食品药品管理局（FDA）批准Sabril（氨己烯酸）口服溶液治疗1个月至2岁儿童的婴儿痉挛症（IS）；Sabril片剂与其它药物联合用药，治疗成人复杂局部性癫痫发作（CPS）。

婴儿痉挛症属于难治性的癫痫综合症，多数是因脑部器质性病变或遗传性代谢疾病所引起。Sabril是FDA批准的第一个婴儿痉挛症的治疗药物，被认定为罕见病治疗药物。

Sabril Information:
SABRIL is an epilepsy medication. Sabril is a brand name used by Aventis for its seizure medicine. The generic name is vigabatrin (vi-GAY-buh-trin). This medication has not been approved by the Food and Drug Administration (FDA) in the United States, but it has been available in other countries for many years. Sabril was developed by a research laboratory in France in 1977. Unlike many other seizure medicines, which are discovered by accident, it was purposely developed with a specific plan in mind—preventing the breakdown of GABA, a neurotransmitter that inhibits brain activity. Sabril was first marketed in Europe in the late 1980s and was approved in Australia in 1993 and in Canada in 1994. In April, 2004, Ovation Pharmaceuticals announced that it had arranged to buy the North American rights to Sabril and planned to try to get FDA approval for sale in the United States. This process is likely to take 2 to 3 years, however. Unfortunately, as many as 25% of patients who take it for a long time suffer damage to the retina of the eye, which limits their field of vision. Because of this safety issue, the FDA has refused to approve Sabril, and its use has been restricted in some other countries. The name or appearance may differ from place to place. The dose (measured in milligrams, abbreviated "mg") will usually be the same. This description applies to the Canadian version: Tablets 500-mg off-white oval tablet Follow your doctor's directions. Call if you have any questions. Sabril is usually taken once or twice a day, in addition to any other seizure medicine you have been taking. You probably will be told to continue taking that medicine in the same way as usual. It's OK to take Sabril either with food or without food. Food does not affect how well it works. Store the tablets at room temperature and away from moisture (not in the bathroom, for instance). Be sure to take only the amount that your doctor tells you to take. If you think you've taken one or two extra pills, call your doctor. For a larger overdose, call your local poison control center or emergency room right away. Don't stop taking Sabril or change the number of tablets you take without talking to your doctor first. Stopping any seizure medicine all at once can cause serious problems. What if I forget? Ask the doctor what to do if you forget a dose. A forgotten dose should be taken right away, unless it is almost time for the next one. In that case, just use one dose, not a double dose, and call the doctor's office for more advice. Do your best to follow the doctor's directions. If you forget doses often, it may be a good idea to get a special pillbox or watch with an alarm to remind you. Taking the right amount of seizure medicine on time every single day is the most important step in preventing seizures

Indication(s):

Tabs: Adjunctive therapy in adult patients with refractory complex partial seizures (CPS) who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss. Not a first line agent for CPS.
Soln: Monotherapy for infantile spasms in patients ages 1 month–2 years, when the potential benefits outweigh the risk of vision loss.

Pharmacology:

Vigabatrin irreversibly inhibits GABA transaminase, which catalyses the metabolism of this inhibitory neurotransmitter. This causes an increase in GABA levels in the CNS, but its exact mechanism in treating seizures is still unknown.

Clinical Trials:

Two studies were conducted to assess the effectiveness of vigabatrin as adjunctive therapy for CPS in adults. Efficacy was measured by examining the reduction in median monthly frequency of CPS plus partial seizures secondarily generalized at the end of study, compared to baseline. The proportion of patients achieving any level of reduction in seizure frequency was consistently higher for vigabatrin compared to placebo; vigabatrin treatment was shown to be significantly superior to placebo in reducing seizure frequency.

Two studies were conducted in patients <2 years of age to assess the efficacy of vigabatrin for infantile spasms. In the first study, the primary efficacy endpoint was the proportion of infants who were spasm-free for 7 consecutive days within the first 14 days of therapy. Seven percent of the 114 patients treated with a low dose of vigabatrin were spasm-free, compared to 15.9% for the high-dose group. In a second study, a statistically significant difference in overall percentage of reduction in spasms was found between the group given vigabatrin versus those given placebo.

SABRIL TABLETS

Legal Classification:

Rx

Adults:

>18 years: Use tabs. Initially 500mg twice daily; titrate if needed by 500mg per week to 1.5g twice daily. CrCl >50–80mL/min: reduce dose by 25%; CrCl >30–50mL/min: reduce dose by 50%; CrCl >10–<30mL/min: reduce dose by 75%. Reevaluate periodically. Withdraw gradually (reduce by 1g/day at weekly intervals).

Children:

<1 month: not recommended. 1month–2 years: use soln. Initially 50mg/kg/day twice daily; titrate by 25–50mg/kg/day at 3-day intervals to max 150mg/kg/day. Renal dysfunction: reduce dose (see literature). Withdraw gradually (reduce by 25–50mg/kg every 3–4 days).

Warnings/Precautions:

Monitor vision, including visual acuity and dilated indirect ophthalmoscopy, and visual fields, at baseline (within 4 weeks) and every 3 months, and for 3–6 months after discontinuing; risk of vision loss increases as dose and cumulative exposure increased. Discontinue if no substantial benefit after treating for 3 months (in adults) or 2–4 weeks (in infants); sooner if obvious treatment failure. Monitor for depression, suicidal ideation, changes in mood/behavior. Elderly. Pregnancy (Cat.C). Nursing mothers: not recommended.

Interaction(s):

May antagonize phenytoin. Avoid others that can cause visual or ophthalmic dysfunction. May interfere with liver function tests (eg, ALT), others (see literature).

Adverse Reaction(s):

Vision loss (may be severe and permanent), other visual changes (blurring, diplopia, asthenopia, eye pain), headache, nystagmus, anemia, somnolence, fatigue, peripheral neuropathy, weight gain, edema, arthralgia, dizziness, tremor, CNS/neurological effects, rash; abnormal MRI signal changes in infants.

Notes:

Available only through restricted distribution program. To register call (888) 45-SHARE. Encourage pregnant patients exposed to vigabatrin to call (888) 233-2334. To report ADRs: (800) 455-1141.

How Supplied:

Tabs—100
Pwd packets—50

Sabril(氨乙烯酸，vigabatrin)片和口服液

批准日期：1998年10月12日欧盟EMEA，2009年8月21日美国FDA。公司：Lundbeck Inc.

一般描述：

氨乙烯酸是γ-氨基丁酸(GABA)同系物。是不可逆GABA-转氨酶抑制剂，此酶负责GABA降解代谢。分子式：C6H11NO2；分子量：29.15704[g/mol]。结构式：
 
适应证：为抗癫痫药(AED)适用于治疗成年难治性复杂性部分癫痫发作。反应不佳患者中用作为可供选择的辅助治疗。
剂量和用法：成年难治性复杂性部分癫痫发作：初始治疗每天2次500 mg，增加至每天总量。推荐剂量是1.5克每天2次。肾受损患者建议调整剂量，终止时逐步减少剂量。
禁忌证：无。
不良反应：用氨乙烯酸对照试验中成年最常见不良反应(超过安慰剂5%)除永久丧失视力外，是疲劳、嗜睡、眼球震颤、震颤、视力模糊、记忆缺陷、增重、关节痛、异常共济失调和精神混乱状态。
黑框警告：视力丧失：SABRIL引起高百分率的患者发生进行和永久双侧中心视野收缩。某些病例中还可减低视力。随总剂量和时间风险增加，但已知不暴露于SABRIL则无视力丧失风险。但只要使用本品继续发生新视力丧失和变坏，有永久丧失视力风险，只能经专门限定分配计划获得ABRIL。