Increased Levetiracetam Clearance Associated with a Breakthrough Seizure in a Pregnant Patient Receiving Once/Day Extended-Release Levetiracetam

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Abstract

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.

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