Levetiracetam

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LVT可能渗透入母乳中（以潜在的能引起临床表现的浓度） LVT probably cross the placenta in potentially clinically important amounts (one Class I and supporting Class II studies or two or more Class II studies). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193. 妊娠可能导致LVT浓度下降（一项Ⅱ类研究）。 Pregnancy possibly causes a decrease in the level of LVT (one Class II study). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193. 可以考虑监测LVT的水平（Level C）。 Monitoring of LVT levels during pregnancy may be considered (Level C). Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, Hopp J, Ting TY, Hauser WA, Thurman D, Kaplan PW, Robinson JN, French JA, Wiebe S, Wilner AN, Vazquez B, Holmes L, Krumholz A, Finnell R, Shafer PO, Le Guen C; American Academy of Neurology; American Epilepsy Society. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009 Jul 14;73(2):142-9. doi: 10.1212/WNL.0b013e3181a6b325. Epub 2009 Apr 27. PMID: 19398680; PMCID: PMC3475193. 对于患有遗传性（特发性全身性）癫痫合并抑郁症（服用或未服用抗抑郁药）的女性患者，首选治疗方案为拉莫三嗪，左乙拉西坦为二线治疗方案。对于唑尼沙胺、丙戊酸盐、托吡酯和拉考沙胺的治疗尚未达成共识。 The experts were asked to rank the appropriateness of various antiseizure drugs or interventions as monotherapy in a woman with depression (who may or may not be on an antidepressant) with genetically mediated (idiopathic generalized) epilepsy. The treatment of choice was lamotrigine, while levetiracetam was considered second-line therapy. No consensus could be reached regarding treatment with zonisamide, valproate, topiramate, and lacosamide. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有局灶性癫痫合并抑郁症（服用或未服用抗抑郁药）的女性患者，拉莫三嗪为首选治疗，奥卡西平和拉考沙胺也可作为一线治疗，卡马西平、艾司利卡西平、左乙拉西坦和唑尼沙胺为二线治疗。 The experts were asked to rank the appropriateness of various anti-seizure drugs or interventions as monotherapy in a woman with depression (who may or may not be on an antidepressant) with focal (symptomatic localization related) epilepsy. Lamotrigine was the treatment of choice, oxcarbazepine and lacosamide were considered first-line therapy, and carbamazepine, eslicarbazepine, levetiracetam, and zonisamide were considered second-line therapy.Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319.

对于患有遗传性（特发性全身性）癫痫的育龄期、有怀孕计划的女性患者，拉莫三嗪和左乙拉西坦是首选治疗方案，唑尼沙胺和托吡酯为二线治疗方案。 The experts were asked to rank the appropriateness of various antiseizure drugs or interventions as monotherapy in a healthy woman in her reproductive years with genetically mediated (idiopathic generalized) epilepsy who is not currently pregnant or trying to conceive but wishes to have a family someday. Lamotrigine and levetiracetam were the treatments of choice; zonisamide and topiramate were considered second-line options. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有局灶性癫痫的育龄期、有怀孕计划的女性患者，奥卡西平为首选治疗方案，拉莫三嗪和左乙拉西坦也是治疗选择 Lamotrigine and levetiracetam were the treatments of choice, with oxcarbazepine considered first-line treatment. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有遗传性（特发性全身性）癫痫的计划怀孕并母乳喂养的女性患者，拉莫三嗪和左乙拉西坦是首选治疗方案，唑尼沙胺为二线治疗方案。 Lamotrigine and levetiracetam were the treatments of choice; zonisamide was considered second-line therapy. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有局灶性癫痫的计划怀孕并母乳喂养的女性患者，奥卡西平为首选治疗方案，拉莫三嗪和左乙拉西坦也是治疗选择；卡马西平、拉考沙胺、艾司利卡西平和唑尼沙胺为二线选择。 Lamotrigine and levetiracetam were the treatments of choice, with oxcarbazepine considered first-line treatment. Carbamazepine, lacosamide, eslicarbazepine, and zonisamide were considered second-line options. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有遗传性（特发性全身性）癫痫合并抑郁症（服用或未服用抗抑郁药）的女性患者，首选治疗方案为拉莫三嗪，左乙拉西坦为二线治疗方案。对于唑尼沙胺、丙戊酸盐、托吡酯和拉考沙胺的治疗尚未达成共识。 The experts were asked to rank the appropriateness of various antiseizure drugs or interventions as monotherapy in a woman with depression (who may or may not be on an antidepressant) with genetically mediated (idiopathic generalized) epilepsy. The treatment of choice was lamotrigine, while levetiracetam was considered second-line therapy. No consensus could be reached regarding treatment with zonisamide, valproate, topiramate, and lacosamide. Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319. 对于患有局灶性癫痫合并抑郁症（服用或未服用抗抑郁药）的女性患者，拉莫三嗪为首选治疗，奥卡西平和拉考沙胺也可作为一线治疗，卡马西平、艾司利卡西平、左乙拉西坦和唑尼沙胺为二线治疗。 The experts were asked to rank the appropriateness of various anti-seizure drugs or interventions as monotherapy in a woman with depression (who may or may not be on an antidepressant) with focal (symptomatic localization related) epilepsy. Lamotrigine was the treatment of choice, oxcarbazepine and lacosamide were considered first-line therapy, and carbamazepine, eslicarbazepine, levetiracetam, and zonisamide were considered second-line therapy.Shih JJ, Whitlock JB, Chimato N, Vargas E, Karceski SC, Frank RD. Epilepsy treatment in adults and adolescents: Expert opinion, 2016. Epilepsy Behav. 2017 Apr;69:186-222. doi: 10.1016/j.yebeh.2016.11.018. Epub 2017 Feb 23. PMID: 28237319.

除拉莫三嗪、左乙拉西坦、奥卡西平、普瑞巴林外，其余AEDs均为妊娠期女性癫痫患者慎用药物，其中丙戊酸为禁用药物。 Mauri Llerda JA, Suller Marti A, de la Peña Mayor P, Martínez Ferri M, Poza Aldea JJ, Gomez Alonso J, Mercadé Cerdá JM. The Spanish Society of Neurology's official clinical practice guidelines for epilepsy. Special considerations in epilepsy: comorbidities, women of childbearing age, and elderly patients. Neurologia. 2015 Oct;30(8):510-7. English, Spanish. doi: 10.1016/j.nrl.2014.08.002. Epub 2015 Jan 21. PMID: 25618222. 应在妊娠期监测AEDs血药水平，其中以拉莫三嗪、左乙拉西坦和奥卡西平血药浓度下降最为明显，在妊娠期和产后可能需要剂量调整。 Importantly, blood drug levels should be monitored because pregnancy can have a major impact on pharmacoki-netic properties of AEDs (e.g., altered absorption,increased distribution volume and renal excretion, and induction of hepatic metabolism).Lamotrigine,levetiracetam and oxcar-bazepine serum concentrations decline most markedly, and dose adjustments may be necessary during pregnancy and postpartum. 孕妇应首选拉莫三嗪和左乙拉西坦，因为这两种药物致畸率最低，但对神经发育的影响尚不明确（数据有限）。推荐卡马西平为替代药物（卡马西平显示出比拉莫三嗪更高的致畸率，但对神经发育没有影响），奥卡西平也可作为替代药物（致畸率很低，但对神经发育的影响上无充分数据）。 Lamotrigine and levetiracetam are first-choice treatment options in pregnant women (and women of childbearing potential) because they carry the lowest risk of major con-genital malformations and have no known impact on neu-robehavioral development (although data for levetiracetam are still limited). Carbamazepine is recommended as alternative first choice; it shows higher malformation rates than lamotrigine and levetiracetam but no impact on neu-rodevelopment. Oxcarbazepine could also be consid-ered; malformation rates are low but data on neurobehavioral development are sparse.

对新生儿应观察是否出现与AEDs相关的副作用，如苯巴比妥可导致新生儿觉醒程度降低和嗜睡，丙戊酸可能与新生儿易激惹相关，拉莫三嗪可能会诱发新生儿皮疹。与透过胎盘屏障的药物浓度相比，丙戊酸、苯巴比妥、苯妥英钠、卡马西平、拉莫三嗪、托吡酯等药物在母体乳汁内的药物浓度较低，对胎儿的影响相对较小，但左乙拉西坦在乳汁内浓度较高，相关风险有待进一步临床研究证实。大部分患者在医生指导下，可进行母乳喂养。在母乳喂养过程中，如出现长时间的镇静、对喂养不感兴趣、体质量不增加等表现，则应立即停止母乳喂养。 中国医师协会神经内科分会癫(癎)专委会. "妊娠期女性抗癫(癎)药物应用中国专家共识." 中国医师杂志 17.7(2015):969-971.

孕前咨询：告知患者癫痫发作及AEDs对妊娠及胎儿风险。妊娠期使用AEDs可能对癫痫女性后代智力发育造成影响，尤其是苯巴比妥和丙戊酸。目前尚无足够的证据来评估新型AEDs（加巴喷丁、左乙拉西坦、噻加宾、托吡酯、氨己烯酸）的致畸性。大剂量丙戊酸（超过800mg/天）以及联合丙戊酸的多药治疗的致畸风险明显增加；告知患者补充叶酸和维生素K的必要性。如果孕妇或者配偶有癫痫疾病，尤其是有特发性癫痫及癫痫及相关遗传病家族史者，应当进行遗传咨询。 Li, S. and Hong, Z., 2015. Lin chuang zhen liao zhi nan. Beijing: Ren min wei sheng chu ban she.

左乙拉西坦

以下情况可能不需要在女孩和WOCP中更换或停用VPA：存在VPA替代品的禁忌证（患有严重活动性抑郁症患者不能换用左乙拉西坦，对拉莫三嗪过敏等）。 The expert panel agrees that there is a scenarios in which valproate may not need to be switched or discontinued in girls and WOCP. Cases in which suitable alternatives are contraindicated. Suitable alternatives to valproate may be contraindicated in certain cases, such as patients with severe active depression (who should not be required to switch to levetiracetam) or patients with a history of allergy to lamotrigine. In such cases, the decision to switch or discontinue valproate can be postponed. Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, Biraben A, Schmitz B. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective. J Neurol. 2020 Apr 1. doi: 10.1007/s00415-020-09809-0. Epub ahead of print. PMID: 32239268. 根据EURAP已知的MCM风险，推荐4种AEDs作为局灶性癫痫的替代物：左乙拉西坦、拉莫三嗪、奥卡西平、卡马西平。其中对卡马西平的剂量限制尤为重要。不推荐使用托吡酯、苯妥英和巴比妥酸盐。 Four AEDs can be recommended as alternatives for focal epilepsy based on known risks of MCMs from the EURAP registry. These are levetiracetam, lamotrigine, oxcarbazepine, and carbamazepine. Dose restriction is especially important in carbamazepine. Topiramate, phenytoin, and barbiturates cannot be recommended due to their teratogenic potential. There are insufficient data for the remaining AEDs, but this does not mean they are safe. Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, Biraben A, Schmitz B. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective. J Neurol. 2020 Apr 1. doi: 10.1007/s00415-020-09809-0. Epub ahead of print. PMID: 32239268. Recommendations for valproate switching and discontinuation in IGE VPA换药和停药的关键时期时青春期前、月经初潮时和怀孕前。专家小组认为，在患者10岁左右（月经初潮前）应推荐患者更换VPA为其他AEDs。对于VPA治疗有效的育龄期患者，可以停用、减量或与拉莫三嗪/左乙拉西坦联合使用，从而减少VPA用量。VPA换药应在怀孕前一年开始，换药速度应视具体情况决定。当患者体内已清除VPA（上次服药后1个月）、没有癫痫发作（基于癫痫复发风险，无发作时间为之前癫痫发作间隔的3倍）时可以考虑尝试怀孕。新的AEDs的剂量调整应基于临床特征，为了平衡有效性和药物耐受性，建议至少3个月。 Valproate switching and discontinuation generally occurs at certain relevant life stages. The three crucial periods are before puberty, at menarche, and before pregnancy. Valproate switching or discontinuation should be recommended in pre-menarche patients (around 10 years of age) after discussion of relevant issues with the patient and her parents/legal guardians. Family planning should be discussed with adult patients of childbearing potential. In patients responsive to valproate only, it could be discontinued, reduced, or combined with lamotrigine or levetiracetam, thus reducing valproate dosage. Valproate switching should ideally be started about 1 year ahead of pregnancy. The speed with which the switch is made, however, should be decided on a case-by-case basis depending on how strong the woman’s desire is to become pregnant. Following valproate discontinuation, patients should not try to conceive until (1) their body is clear of valproate (at least 1 month since last intake) and (2) they are free of seizures (based on seizure recurrence risk, three times the previous interval between seizures). Dose adjustments for the new AED should be based on clinical features; a period of at least 3 months is recommended for balancing efectiveness and tolerability. Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, Biraben A, Schmitz B. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective. J Neurol. 2020 Apr 1. doi: 10.1007/s00415-020-09809-0. Epub ahead of print. PMID: 32239268. Recommendations for valproate switching and discontinuation in IGE 从VPA换为LTG平均需要2-3个月甚至更长的时间。应根据临床特征和血清LTG浓度进行滴定（LTG titration）。 从VPA转换到LEV更快，且通常不需要滴定。LEV目标剂量在1000-2000mg/d之间，具体取决于VPA剂量。 Switching from valproate to lamotrigine requires on average 2–3 months, but it can take much longer. Lamotrigine titration should be guided by clinical response and, where available, serum concentrations. Switching from valproate to levetiracetam is faster, as titration is not needed. The target dose for levetiracetam is between 1000 and 2000 mg/day depending on the valproate dose. Toledo M, Mostacci B, Bosak M, Jedrzejzak J, Thomas RH, Salas-Puig J, Biraben A, Schmitz B. Expert opinion: use of valproate in girls and women of childbearing potential with epilepsy: recommendations and alternatives based on a review of the literature and clinical experience-a European perspective. J Neurol. 2020 Apr 1. doi: 10.1007/s00415-020-09809-0. Epub ahead of print. PMID: 32239268.

A pyrrolidinone and acetamide derivative that is used primarily for the treatment of SEIZURES and some movement disorders, and as a nootropic agent.

A pyrrolidine with antiepileptic activity. The exact mechanism through which levetiracetam exerts its effects is unknown but does not involve inhibitory and excitatory neurotransmitter activity. Stereoselective binding of levetiracetam was confined to synaptic plasma membranes in the central nervous system with no binding occurring in peripheral tissue. Levetiracetam inhibits burst firing without affecting normal neuronal excitability, which suggests that it may selectively prevent hyper-synchronization of epileptiform burst firing and propagation of seizure activity.

Levetiracetam

[GRADES OF RECOMMENDATION:C] Based on limited evidence, in utero exposure to carbamazepine and lamotrigine does not appear to adversely affect neurodevelopment of the offspring. There is very little evidence for levetiracetam and phenytoin. Parents should be informed that evidence on long-term outcomes is based on small numbers of children. 【推荐等级：C】应告知WWE及其伴侣，关于宫内暴露于AEDs产生的长期神经发育结果是基于少数儿童的。有限的证据表示，宫内接触CBZ和LTG似乎不会影响后代神经生长发育；使用LEV和PHT的证据很少。 https://www.rcog.org.uk/guidance/browse-all-guidance/green-top-guidelines/epilepsy-in-pregnancy-green-top-guideline-no-68/

[GRADES OF RECOMMENDATION:D] Parents should be made aware of signs of toxicity in infants of breastfeeding women taking antiepileptic drugs. The possibility of sedation should be considered in infants of mothers taking high dose antiepileptic drugs, polytherapy, or regimens including primidone, levetiracetam, gabapentin, lamotrigine and topiramate. D级推荐：应告知女性癫痫患者及其伴侣，哺乳期服用AEDs可能对新生儿/婴儿有不良影响。服用大剂量AEDs、综合疗法或采用包含扑米酮、左乙拉西坦、加巴喷丁、拉莫三嗪和托吡酯在内的治疗方案的哺乳期母亲婴儿可能会有镇静的副作用。 Scottish Intercollegiate Guidelines Network.Diagnosis and management of epilepsy in adults. SIGN 143. Edinburgh, SIGN, 2015. Available at: www.sign.ac.uk/guidelines/fulltext/143/index.html

Ucb L059 UcbL060 Etiracetam (R)- alpha-ethyl-2-oxo-1-Pyrrolidineacetamide UCB-6474 Ucb L060 UCB6474 Ucb-L060 UCB 6474 R-isomer Etiracetam alpha ethyl 2 oxo 1 Pyrrolidineacetamide Etiracetam R isomer Ucb-L059 Etiracetam Etiracetam R-isomer Levetiracetam-containing product S-isomer Etiracetam Keppra Levetiracetam (substance) (S)-alpha-Ethyl-2-oxo-1-pyrrolidineacetamide Levetiracetam Levetiracetamum 1-pyrrolidineacetamide alpha-ethyl-2-oxo-(S)- Etiracetam S-isomer Levetiracetame Product containing levetiracetam (medicinal product) Etiracetam S isomer 102767-28-2 1-Pyrrolidineacetamide alpha-ethyl-2-oxo- (alphaS)-

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