女性癫痫患者的管理专家讲稿.pptx

女性癫痫患者的长程管理CH/KP/1606/0163 •我国癫痫患病率高达7‰ ，约有900万癫痫患者1•其中近一半为女性患者•23%的癫痫病人为育龄期女性（12-50岁）21.中华神经科杂志. 2013; 46(7): 496-499 2.Joint Epilepsy Council of the UK and Ireland (2011)女性癫痫概述女性癫痫患者需要更多关注中华神经科杂志. 2013; 46(7): 496-499EMA有关VPA的黑框警告CEA-ILAE 2015指南更新女性癫痫患者的药物治疗女性癫痫患者的管理EMA有关丙戊酸（VPA）在具生育潜力女性（包括女童， 女性青少年，育龄期及怀孕女性）中使用的黑框警告“ VPA*不应用于女性儿童、女性青少年、具 生育潜力的女性以及怀孕的女性，除非其他治 疗均无效或不耐受4.4.1 Special warningsFemale children/Female adolescents/Women of childbearing potential/Pregnancy: Epilim should not be used in female children, in female adolescents, in women of childbearing potential and pregnant women unless alternative treatments are ineffective or not tolerated because of its high teratogenic potential and risk of developmental disorders in infants exposed in utero to valproate. The benefit and risk should be carefully reconsidered at regular treatment reviews, at puberty and urgently when a woman of childbearing potential treated with Epilim plans a pregnancy or if she becomes pregnant. Women of childbearing potential must use effective contraception during treatment and be informed of the risks associated with the use of Epilim during pregnancy (see section 4.6). The prescriber must ensure that the patient is provided with comprehensive information on the risks alongside relevant materials, such as a patient information booklet, to support her understanding of the risks. In particular the prescriber must ensure the patient understands: • The nature and the magnitude of the risks of exposure during pregnancy, in particular the teratogenic risks and the risks of developmental disorders. • The need to use effective contraception. • The need for regular review of treatment. • The need to rapidly consult her physician if she is thinking of becoming pregnant or there is a possibility of pregnancy. In women planning to become pregnant all efforts should be made to switch to appropriate alternative treatment prior to conception, if possible (see section 4.6). Valproate therapy should only be continued after a reassessment of the benefits and risks of the treatment with valproate for the patient by a physician experienced in the management of epilepsy.http://www.medicines.org.uk/emc/medicine/26124#CLINICAL_PRECAUTIONS欧洲药品管理局（EMA） 2015年更新的 VPA* SmPC: EMA：European Medicines Agency SmPC：Summaries of Product Characteristics ן胎儿先天畸形 ן影响出生后认知能力发展 ן增加出生后自闭症风险黑框警告主要基于以下三方面证据VPA宫内暴露可能导致一、VPA的胎儿致畸率高三项大型前瞻性抗癫痫药物与怀孕登记研究 （Uklre, NAAPR 和 EURAP） 两项基于人群的研究（NMBR 和 SMBR）VPA： 4.7 – 9.7% 致畸率，另有一meta分析1显示为 10.7%1.Meador et al. Epilepsy Res (2008) ;81:1–13 2.Tomson et al. Epilepsia (2015). 56(7): 1006-1019.注：母亲为癫痫患者的致畸率为 7.1%；普通人群的致畸率 为2.1 – 2.9%二、胎儿期 VPA 暴露阻碍出生后认知能力的发展In the prospective “Neurodevelopmental Effects of Antiepileptic Drugs” (NEAD) study, IQ at age 6 was on average 8–11 points lower in valproate-exposed children compared with children exposed to other AEDs (CZP, LTG, phenytoin). These IQ reductions were considered sufficient to affect education and occupational outcomes in later life. NEAD 研究发现，宫内VPA 暴露患儿，6岁时IQ比其他AED(CZP, LTG, PHT) 低8-11分，IQ降低足以造成未 来教育和就业的影响Meador KJ, Baker GA, Browning N, et al. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol 2013;12:244–252.When considering lower doses of VPA, in the two largest prospective studies, IQ at age 6 among children exposed to valproate at doses below 1,000 mg daily or 800 mg daily was comparable to the IQ of children exposed to other AEDs. In the latter study, however, children exposed to valproate 70且接受单药治疗），且入组时其孩子小 于24个月。

采用Griffiths 精神发育量表评价儿童的智能发育情况既往左乙拉西坦宫内暴露的儿童51例，既往丙戊酸宫内 暴露的儿童44例，普通儿童（其母亲未患癫痫）97例为对照组澳大利亚妊娠登记1998年-2013年期间 左乙拉西坦的临床应用大幅上升Epilepsia, 55(8):1229–1234, 2014该图显示了1998年-2013年间传统及新型AEDs妊娠期临床应用的变化趋势其中左乙拉西坦的临床应用快速上升，卡马西平及丙戊酸的应用下降，拉莫三嗪的应用先有增加，而后相对稳定澳大利亚妊娠登记显示左乙拉西坦控制患者的妊娠期癫痫 发作与传统AEDs 相似，并优于新型AEDsEpilepsia, 55(8):1229–1234, 2014..指南建议：女性癫痫患者可选用左乙拉西坦• 对于青春期患儿…尽量避免使用明显增加体重、影响月经周期或增加将来胚胎致畸风险的 AEDs（如丙戊酸、苯巴比妥等），尽可能选择对体重和月经周期影响较小的AEDs（如 拉莫三嗪，左乙拉西坦等）中国儿童癫痫长程管理专家共识 2013 11.儿科学分会神经学组. 中华儿科杂志 2013; 51(9) : 699-703 2.SIGN （苏格兰学院间指南网络） • Diagnosis and management of epilepsy in adults.• 育龄期女性患者可选用左乙拉西坦SIGN国家临床指南 2015：成人癫痫的诊断和管理2 小结CEA-ILAE 2015指南指出在具生育潜力的女性中应避免使用VPA左乙拉西坦是适合女性癫痫患者的AEDVPA欧洲说明书增加了应用于女性的黑框警告谢 谢!。