Garrity Lisa C, Turner Michele, Standridge Shannon M
Division of Pharmacy, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Pharmacotherapy. 2014 Jul;34(7):e128-32. doi: 10.1002/phar.1439. Epub 2014 May 7.
The use of levetiracetam for the treatment of epilepsy in women of childbearing age has increased as more evidence of teratogenicity of other broad-spectrum antiepileptic medications becomes available. Levetiracetam appears to be associated with a low incidence of major congenital malformations based on data from pregnancy registries. Major pregnancy-related changes in the pharmacokinetics of levetiracetam have been described in several case series, demonstrating a role for careful therapeutic drug monitoring of levetiracetam in pregnant patients. Extended-release levetiracetam provides a way to improve medication adherence in adults with epilepsy by allowing once/day dosing and may be considered for use in pregnancy to minimize the fluctuation of levetiracetam levels throughout the day, thus potentially minimizing dose-related adverse effects. In this case report, we describe a 16-year-old, compliant, pregnant patient who experienced subtherapeutic levetiracetam blood concentrations that occurred with use of extended-release levetiracetam. She experienced a breakthrough seizure with once/day dosing during her third trimester with low subsequent trough levels despite multiple dose increases. After changing to twice/day dosing of extended-release levetiracetam at delivery, the patient experienced no seizures and delivered a healthy infant without complications. This is the first case report, to our knowledge, to describe seizure breakthrough during pregnancy with an extended-release formulation of an antiepileptic medication. Pharmacokinetic changes associated with pregnancy may increase apparent clearance of extended-release formulations of levetiracetam, leading to periods of subtherapeutic blood or central nervous system concentrations. These changes support the important role of therapeutic monitoring of levetiracetam plasma concentrations to help maintain seizure control in women with epilepsy during pregnancy.
随着越来越多其他广谱抗癫痫药物致畸性的证据出现，左乙拉西坦在育龄女性癫痫治疗中的使用有所增加。基于妊娠登记处的数据，左乙拉西坦似乎与严重先天性畸形的低发生率相关。几个病例系列描述了左乙拉西坦药代动力学与妊娠相关的主要变化，表明对妊娠患者进行左乙拉西坦仔细的治疗药物监测具有重要作用。缓释左乙拉西坦通过允许每日一次给药，为改善癫痫成年患者的药物依从性提供了一种方法，并且可考虑在妊娠期间使用，以尽量减少左乙拉西坦水平全天的波动，从而潜在地减少与剂量相关的不良反应。在本病例报告中，我们描述了一名16岁、依从性好的妊娠患者，她在使用缓释左乙拉西坦时出现了低于治疗水平的左乙拉西坦血药浓度。尽管多次增加剂量，但在妊娠晚期她每日一次给药时仍出现了突破性癫痫发作，随后的谷浓度较低。分娩时改为每日两次服用缓释左乙拉西坦后，患者未再发作，并顺利产下一名健康婴儿，无并发症。据我们所知，这是第一例描述抗癫痫药物缓释制剂在妊娠期间出现癫痫突破性发作的病例报告。与妊娠相关的药代动力学变化可能会增加左乙拉西坦缓释制剂的表观清除率，导致血药浓度或中枢神经系统浓度低于治疗水平。这些变化支持了对左乙拉西坦血浆浓度进行治疗监测的重要作用，以帮助维持癫痫女性在妊娠期间的癫痫控制。
