Transfer of lamotrigine into breast milk
School of Medicine and Pharmacology, University of Western Australia, Perth City, Western Australia, AustraliaAnnals of Pharmacotherapy (Impact Factor: 2.06). 07/2006; 40(7-8):1470-1. DOI: 10.1345/aph.1G667
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ABSTRACT: The issue of how much an antiepileptic drug (AED) crosses the placenta and relative safety of lactation in mothers receiving AEDs are common clinical questions. Educating potential mothers with epilepsy regarding available information is warranted so that informed decisions and any needed neonatal monitoring is performed. Unfortunately, there is still limited data regarding the degree in which anticonvulsants cross the placenta and penetrate into breast milk. There is a greater appreciation of the factors that influence AED passive transfer across the placenta and into breast milk, as well as factors that ultimately influence neonatal AED distribution. In general, women with epilepsy can have healthy babies even with significant placental exposure and can breast-feed their babies safely with some cautions. Phenobarbital and primidone should be avoided in parents wishing to breast-feed. For the AEDs ethosuximide, levetiracetam, lamotrigine, topiramate, and zonisamide, there is a potential for significant breast milk concentrations; however, there are no firm guidelines on whether lactation is safe. In all cases, parents should be counseled to monitor their child for side effects and the need for routine monitoring.
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ABSTRACT: Although lamotrigine use during pregnancy has substantially increased over the past decade secondary to accumulated reproductive safety data, systematic data on lamotrigine during breastfeeding remains sparse. We sought to characterize the determinants of lamotrigine concentrations in breast milk and nursing-infant plasma. Women who enrolled in a prospective investigation of perinatal medication pharmacokinetics, were treated with lamotrigine, and chose to continue lamotrigine while breastfeeding were included in the analysis. Breast milk samples were collected via breast pump from foremilk to hindmilk from a single breast to determine the excretion gradient and serial samples over 24 hours to determine the time course of excretion. Paired maternal/infant plasma samples were also collected. Lamotrigine concentrations in all of the samples were determined by using high-performance liquid chromatography with ultraviolet detection. Statistical analyses of breast milk and infant plasma concentrations and their determinants were conducted. Thirty women and their nursing infants participated in the study, providing a total of 210 breast milk samples. The mean milk/plasma ratio was 41.3%. There was a nonsignificant trend for higher lamotrigine concentrations in breast milk 4 hours after the maternal dose. Infant plasma concentrations were 18.3% of maternal plasma concentrations. The theoretical infant lamotrigine dose was 0.51 mg/kg per day, and the relative infant lamotrigine dose was 9.2%. Mild thrombocytosis was present in 7 of 8 infants at the time of serum sampling. No other adverse events were observed or reported in the breastfed infants. Consistent with previous investigations of medications in breast milk, the lamotrigine milk/plasma ratio is highly variable. The rate of lamotrigine excretion into human breast milk is similar to that observed with other antiepileptic drugs. These data expand the extant literature on lamotrigine in breastfeeding and demonstrate relatively comparable nursing-infant exposure to lamotrigine compared with other antiepileptic drugs.
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