Longo Brian, Forinash Alicia B, Murphy Julie A
St. Louis College of Pharmacy, St. Louis, MO 63110, USA.
Ann Pharmacother. 2009 Oct;43(10):1692-5. doi: 10.1345/aph.1M231. Epub 2009 Aug 18.
To review data evaluating levetiracetam management of epilepsy during pregnancy.
A literature search of PubMed (1966-June 2009) was performed using the terms pregnancy, epilepsy, levetiracetam, and anticonvulsants. Bibliographies of all articles retrieved were reviewed to identify additional relevant articles.
All studies including humans and published in English with data describing levetiracetam management during pregnancy were included.
The pharmacokinetic studies included in this review demonstrate that the clearance of levetiracetam increases during pregnancy, particularly during the third trimester, which subsequently leads to decreased serum levetiracetam concentrations. The increase in clearance is most likely due to an increase in renal blood flow. The teratogenic studies included in this review included a total of 147 patients. Of these patients, 2% experienced a major congenital malformation (MCM) and 4.8% experienced a minor anomaly. All of the patients who had either an MCM or a minor anomaly were receiving antiepileptic drug (AED) polytherapy. It was unknown whether 10.9% of the 147 patients discussed were receiving levetiracetam monotherapy or AED polytherapy. None of the published literature assessed adherence to AED therapy. Folic acid supplementation was addressed in only one of the case series presented.
If levetiracetam is used during pregnancy, women should receive adequate amounts of folic acid (0.4-5 mg/day) and serum concentrations of levetiracetam should be determined before conception if possible and during each trimester, especially during the middle of the third trimester, to assess therapeutic concentrations. The dose may need to be increased during the third trimester to provide concentrations consistent with those before conception. Patients should be informed that there appears to be a small chance of malformations with levetiracetam, but that the data are limited.
回顾评估左乙拉西坦在妊娠期癫痫治疗中的相关数据。
利用“妊娠”“癫痫”“左乙拉西坦”和“抗惊厥药”等检索词对PubMed（1966年至2009年6月）进行文献检索。对所有检索到文章的参考文献进行审查以识别其他相关文章。
纳入所有包含人类受试者且以英文发表、有关于妊娠期左乙拉西坦治疗数据的研究。
本综述纳入的药代动力学研究表明，左乙拉西坦的清除率在妊娠期增加，尤其是在孕晚期，这随后导致血清左乙拉西坦浓度降低。清除率增加最可能是由于肾血流量增加。本综述纳入的致畸性研究共涉及147例患者。其中，2%发生了严重先天性畸形（MCM），4.8%出现了轻微异常。所有发生MCM或轻微异常的患者均接受了抗癫痫药物（AED）联合治疗。尚不清楚所讨论的147例患者中有10.9%是接受左乙拉西坦单药治疗还是AED联合治疗。已发表的文献均未评估AED治疗的依从性。仅其中一个病例系列讨论了叶酸补充问题。
如果在妊娠期使用左乙拉西坦，女性应摄入足量叶酸（0.4 - 5毫克/天），并且如果可能，在受孕前以及妊娠各期，尤其是孕晚期中期，测定左乙拉西坦的血清浓度以评估治疗浓度。孕晚期可能需要增加剂量以维持与受孕前一致的浓度。应告知患者，左乙拉西坦似乎有致畸的小风险，但相关数据有限。
