Abstract
ObjectivesTo evaluate the pharmacokinetic changes in lamotrigine (LTG) from prepregnancy to postpartum and to assess the impact of therapeutic drug monitoring (TDM) on seizure management during pregnancy in a Chinese population.MethodsA series of women who were on LTG monotherapy before conception or during pregnancy were included in this retrospective study. The clinical characteristics of the mothers and fetuses were collected. The apparent clearance (AC) and the ratio to target concentration (RTC) were calculated for each trimester or for each month. RTCs were compared between patients with and without an increase in the frequency of seizures. A receiver operating characteristic curve to determine the RTC threshold, which predicts increased seizure frequency best, was drawn.ResultsA total of 12 patients and their 12 pregnancies were reviewed retrospectively. AC increased by 82.5% during the first trimester (p = 0.0343), 203.2% during the second trimester (p = 0.0010), and 197.0% during the third trimester (p = 0.0061) compared with the prepregnancy level. The value returned to the prepregnancy level after delivery. Seven patients who had adequate baseline information were included to examine the association between serum LTG concentration and seizure frequency. The RTC values of patients with and without an increased frequency of seizures were significantly different (p = 0.0164), and increased seizure frequency was associated with a lower RTC. An RTC < 0.64 was a predictor of deteriorating seizures.ConclusionsThe pharmacokinetic changes in LTG during pregnancy displayed marked interpatient variation. TDM can support a rational treatment plan for LTG use during pregnancy. We recommend regular monitoring of LTG serum concentrations from prepregnancy to postpartum.
Highlights
Epilepsy during pregnancy poses a special challenge to neurologists worldwide
Previous studies have reported that the pharmacokinetics of LTG are substantially affected by pregnancy (Fotopoulou et al, 2009; Milosheska et al, 2016; Pennell et al, 2004, 2008; Polepally et al, 2014; Reisinger, Newman, Loring, Pennell, & Meador, 2013), so a dose adjustment may be needed under therapeutic drug monitoring (TDM) during pregnancy
The aims of the present study were to evaluate the pharmacokinetic changes in LTG from prepregnancy to postpartum and to assess the impact of TDM on seizure management during pregnancy in a Chinese population
Summary
Epilepsy during pregnancy poses a special challenge to neurologists worldwide. The treatment must balance the risk of seizures with the potential for adverse effects from drug use which may affect both the mother and developing fetus (Bech et al, 2014; Cohen‐Israel et al, 2018; Vajda et al, 2017). Lamotrigine (LTG) is a second‐generation antiepileptic drug (AED) with broad spectrum. It is considered an ideal AED administered to women of childbearing age and during pregnancy (Yasam et al, 2016). Previous studies have reported that the pharmacokinetics of LTG are substantially affected by pregnancy (Fotopoulou et al, 2009; Milosheska et al, 2016; Pennell et al, 2004, 2008; Polepally et al, 2014; Reisinger, Newman, Loring, Pennell, & Meador, 2013), so a dose adjustment may be needed under therapeutic drug monitoring (TDM) during pregnancy. The aims of the present study were to evaluate the pharmacokinetic changes in LTG from prepregnancy to postpartum and to assess the impact of TDM on seizure management during pregnancy in a Chinese population
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