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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存在的重要安全性问题是视觉损伤。Sabril药品说明书[黑框警告]中警示医生，使用Sabril存在发生进行性周边视觉丧失的风险，可能导致视力衰退。视觉损伤风险与Sabril使用剂量和时间增加有关，但即使最低剂量的Sabril也可能引起视觉损伤。因此服用Sabril病人必须进行定期视力检查。
由于有造成永久性视觉损伤风险，Sabril的销售程序有严格的规定性要求。
Manufacturer:
Lundbeck, Inc.
Pharmacological Class:AntiepilepticActiveIngredient(s):Vigabatrin 500mg; tabs.
Also:SABRIL for ORAL SOLUTIONVigabatrin500mg/packet; pwd for oral soln.
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 ofvigabatrin as adjunctivetherapy for CPS in adults. Efficacy was measured byexamining 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 besignificantly superior to placebo in reducing seizure frequency.
Two studies were conducted in patients <2 years of age to assess the efficacy of vigabatrinforinfantile 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.
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–2years:usesoln.Initially50mg/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).
Precaution(s):Monitor vision, including visual acuity and dilatedindirectophthalmoscopy, and visual fields, at baseline (within 4 weeks) and every 3 months, and for 3–6 monthsafterdiscontinuing; 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, suicidalideation,changesinmood/behavior. Elderly. Pregnancy (Cat.C).
Nursing mothers: not recommended.
Interaction(s):May antagonize phenytoin. Avoidothers 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,peripheralneuropathy,weightgain,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
Last Updated:10/22/2009
氨己烯酸 〖药物名称〗: 氨己烯酸
〖别 名〗:
〖英 文 名〗: Vigabatrin
〖药品说明〗: 片剂每片500mg。
〖功用主治〗:
本品具有抗癫痫作用，其作用机制为，不可逆地抑制GABA氨基转移酶（GABA-T），提高脑内GABA浓度而发挥作用。临床研究结果表明，氨己烯酸为治疗严重癫痫患儿有效而安全的一种抗癫痫药，并对智力障碍的癫痫患者亦有效。
本品口服吸收迅速，食物不影响其吸收速度。服药2小时后达血药高峰浓度，t1/2为5～7小时，单剂服用1～3g，药动学呈剂量-线性关系，表观分布容积约为0.8L／kg，相对生物利用度为92±11％。
本品适用于治疗顽固性部分性癫痫发作，尤其对顽固性儿童癫痫发作适用。
〖用法用量〗: 口服成人和9岁以上儿童为每日2g，每日2次，需要时可增加到每日4g，每日最大剂量4g。3～9岁儿童，建议剂量为每日1g。
〖注意要点〗:
（1）不良反应可有嗜睡、共济失调、头痛、头晕、情绪激动、记忆障碍及体重增加，但绝大部分病人未见到这些不良反应。
（2）合用时，本品可使苯妥英钠、苯巴比妥和扑米酮的血药浓度分别降低20％、7％和11％。当本药与苯妥英钠合用时，苯妥英钠剂量需增加（但苯巴比妥与扑米酮与本品合用时不需增加剂量）。 |
