摘要： 目的  调查四川地区左乙拉西坦、托吡酯、奥卡西平和拉莫三嗪等新型抗癫痫药物在儿童癫痫患者中超说明书规定用药（超说明书用药）的现状及安全性，以为临床制定相关用药指南提供数据，并为临床用药提供参考。方法  收集2010 年7 月-2011 年11 月于四川大学华西第二医院、成都市妇女儿童中心医院和四川省人民医院门诊接受抗癫痫药物治疗的儿童癫痫患者资料，统计此间应用抗癫痫药物的总病例数和服用4 种新型抗癫痫药物的病例数。依据药品说明书适应证，判断使用新型抗癫痫药物的医嘱是否属于超说明书用药及其药物类型，并计算和分析超说明书用药发生率及药物不良反应。结果  共854 例癫痫患儿接受抗癫药物治疗，其中670 例患儿服用4种新型抗癫痫药物中的一种或多种，超说明书用药者406 例，占抗癫痫药物治疗总病例数的47.54%（406/854），约占新型抗癫痫药物治疗总病例数的60.60%（406/670）。与按说明书用药患儿相比，超说明书用药患儿年龄更小、单药使用比例更高、全面性发作和癫痫综合征患儿比例更高，其病例数比例分别为左乙拉西坦78.50%（157/200）、托吡酯79.81%（253/317）、奥卡西平21.32%（42/197）和拉莫三嗪33.33%（21/63）；不同年龄、单药使用和各种发作类型中以左乙拉西坦和托吡酯超说明书用药现象更为突出。除失访病例外，超说明书用药组患儿以奥卡西平［16.67%（7/42）］不良反应发生率最高，其次分别为托吡酯［14.81%（36/243）］、左乙拉西坦［10.60%（16/151）］和拉莫三嗪［9.52%（2/21）］，但是与按说明书用药组之间差异无统计学意义（χ² = 0.375、0.448、0.014、0.109，P = 0.540、0.503、0.906、0.742）。结论  在四川地区儿童癫痫患者中超说明书应用新型抗癫痫药物的发生率较高，其中以托吡酯和左乙拉西坦尤为突出，但新型抗癫痫药物在一定范围内超说明书用药仍具有较好的安全性和耐受性。

关键词: 抗惊厥药； 药物标签； 癫痫； 处方, 药物； 药物毒性； 儿童

Abstract: Objective To investigate current status and safety about off-label use of levetiracetam, topiramate, oxcarbazepine, lamotrigine among pediatric patients in Sichuan area, so as to provide baseline data for formulating guidelines of off-label drug use. Methods Medical records of pediatric epileptic patients receiving antiepileptic drugs (AEDs) from July 2010 to November 2011 were collected at the following hospitals: West China Second University Hospital of Sichuan University, Chengdu Women's and Children's Central Hospital and Sichuan Provincial People's Hospital. The numbers of patients receiving AEDs and novel AEDs were calculated. Off-label drug use and the category of off-label drug use were judged according to the indications listed in drug instructions. The incidence of off-label drug use was calculated. The patients receiving novel AEDs were devided into on-label and off-label use groups; the clinical characteristics of these two groups were summarized and adverse reactions of two groups were compared by using χ² test. Results During the study period, there were totally 854 patients receiving AEDs including 670 patients receiving novel AEDs. Among 670 patients 406 patients off-label use group received off-label use of novel AEDs, accounting for 47.54% (406/854) of the total patients receiving AEDs and 60.60% (406/670) of patients receiving novel AEDs. When compared with on-label use group, off-label use group had more younger patients, more patients with single-drug use and more patients with generalized epilepsy or epileptic syndrome. The rates of off-label using drug were levetiracetam 78.50% (157/200), topiramate 79.81% (253/317), oxcarbazepine 21.32% (42/197) and lamotrigine 33.33% (21/63). The off-label use of levetiracetam and topiramate occured in all three aspects: age, single-drug use and seizure type. The adverse reaction rates of off-label use were oxcarbazepine 16.67% (7/42), topiramate 14.81% (36/243), levetiracetam 10.60% (16/151), lamotrigine 9.52% (2/21). When compared with the adverse reaction rates of on-label use group, the difference was not statistically significant (the values of χ² were 0.375, 0.448, 0.014, 0.109 respectively and the values of P were 0.540, 0.503, 0.906, 0.742 respectively). Conclusion Among pediatric patients in Sichuan area, the rate of off-label use of novel AEDs was very high, especially for topiramate and levetiracetam. The follow-up data of this survey suggested that off-label use of novel AEDs with careful observation for adverse reactions had good safety and tolerance.

Key words: Anticonvulsants, Drug labeling, Epilepsy, Prescriptions, drug, Drug toxicity, Child