Joyce Liporace1, Amy Kao, Anelyssa D'Abreu. 1. Department of Neurology, Jefferson Medical College, Philadelphia, PA, USA. Joyce.Liporace@jefferson.edu
Abstract
PURPOSE: Many women with epilepsy who are planning a pregnancy are treated with lamotrigine (LTG), resulting in greater fetal exposure to the drug. Current care guidelines suggest that mothers with epilepsy breast-feed their children. These recommendations are made without regard to how nursing newborns metabolize medication. Lamotrigine is extensively metabolized by glucuronidation, which is immature in neonates and may lead to accumulation of medication. This article reports LTG levels in full-term nursing newborns born to mothers with epilepsy on lamotrigine monotherapy. METHODS: Serum LTG levels were obtained in nursing mothers and their neonates on Day 10 of life. Maternal LTG clearance during pregnancy and postpartum was determined and correlated with levels. RESULTS: Four mothers with partial epilepsy on LTG monotherapy were evaluated. Serum LTG levels in nursing newborns ranged from <1.0 to 2.0 microg/mL on Day 10 of life. Three babies had LTG levels >1.0 microg/mL. After excluding one child with an undetectable level, the LTG levels in newborns were on average 30% (range 20-43%) of the maternal drug level. No decline was noted in two children with repeat levels at 2 months. CONCLUSION: Serum concentrations of LTG in breast-fed children were higher than expected, in some cases reaching "therapeutic" ranges. These high levels may be explained by poor neonatal drug elimination due to inefficient glucuronidation. Our observation that not all newborns had a high LTG level suggests considerable genetic variability in metabolism. Our limited data suggest monitoring blood levels in nursing children and the need for individual counseling for women with epilepsy regarding breast-feeding.
PURPOSE: Many women with epilepsy who are planning a pregnancy are treated with lamotrigine (LTG), resulting in greater fetal exposure to the drug. Current care guidelines suggest that mothers with epilepsy breast-feed their children. These recommendations are made without regard to how nursing newborns metabolize medication. Lamotrigine is extensively metabolized by glucuronidation, which is immature in neonates and may lead to accumulation of medication. This article reports LTG levels in full-term nursing newborns born to mothers with epilepsy on lamotrigine monotherapy. METHODS: Serum LTG levels were obtained in nursing mothers and their neonates on Day 10 of life. Maternal LTG clearance during pregnancy and postpartum was determined and correlated with levels. RESULTS: Four mothers with partial epilepsy on LTG monotherapy were evaluated. Serum LTG levels in nursing newborns ranged from <1.0 to 2.0 microg/mL on Day 10 of life. Three babies had LTG levels >1.0 microg/mL. After excluding one child with an undetectable level, the LTG levels in newborns were on average 30% (range 20-43%) of the maternal drug level. No decline was noted in two children with repeat levels at 2 months. CONCLUSION: Serum concentrations of LTG in breast-fed children were higher than expected, in some cases reaching "therapeutic" ranges. These high levels may be explained by poor neonatal drug elimination due to inefficient glucuronidation. Our observation that not all newborns had a high LTG level suggests considerable genetic variability in metabolism. Our limited data suggest monitoring blood levels in nursing children and the need for individual counseling for women with epilepsy regarding breast-feeding.
Authors: D Jeffrey Newport; Page B Pennell; Martha R Calamaras; James C Ritchie; Melanee Newman; Bettina Knight; Adele C Viguera; Joyce Liporace; Zachary N Stowe Journal: Pediatrics Date: 2008-06-30 Impact factor: 7.124
Authors: Michael Paulzen; Julia C Stingl; Marc Augustin; Helena Saßmannshausen; Cordula Franz; Gerhard Gründer; Georgios Schoretsanitis Journal: Clin Pharmacokinet Date: 2019-04 Impact factor: 6.447