Lamotrigine in Breast Milk and Nursing Infants: Determination of Exposure

Abstract

OBJECTIVE-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.PATIENTS AND METHODS-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 Address correspondence to D. Jeffrey Newport, MD, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1365 Clifton Rd NE, Suite B6100, Atlanta, GA 30322. jeff.newport@emory.edu. Financial Disclosure: Dr Newport has received research support from Eli Lilly, GlaxoSmithKline, Janssen, Wyeth, the National Alliance for Research on Schizophrenia and Depression, and the National Institutes of Health and speaker's honoraria from AstraZeneca, Eli Lilly, GlaxoSmithKline, and Pfizer; Dr Pennell has received research support from GlaxoSmithKline, the National Institutes of Health, Marinus Pharmaceuticals, and UCB Pharma, has served on advisory boards for GlaxoSmithKline and UCB Pharma, and received speaker's honoraria from GlaxoSmithKline and UCB Pharma; Ms Calamaras has received National Institutes of Health research support; Dr Ritchie has received research support from GlaxoSmithKline and has served on advisory boards for CeNeRx Pharma and Abaxis; Ms Newman has received research support from GlaxoSmithKline, the National Institutes of Health, Marinus Pharmaceuticals, and UCB Pharma; Ms Knight has received research support from Bristol-Myers Squibb, Cyberonics, Eli Lilly, Forest, Janssen, the National Institutes of Health, Novartis, and Wyeth; Dr Viguera has received research support from the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression, a Harvard Medical School Scholars in Medicine Fellowship Award (Claflin Award), the Stanley Medical Research Institute, Astra-Zeneca, Berlex Laboratories, Eli Lilly, Forest, Pfizer, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sepracor, and Wyeth, has served on advisory boards to GlaxoSmithKline, Novartis, and Wyeth, and received speakers' honoraria from Astra-Zeneca, Eli Lilly, GlaxoSmithKline, Novartis, and Wyeth; Dr Liporace receives research support from the National Institutes of Health and is on the speaker's bureau and advisory board for UCB Pharma and GlaxoSmithKline but does not receive financial compensation for these services; and Dr Stowe has received research support from GlaxoSmithKline, the National Institutes of Health, and Wyeth, served on advisory boards for Wyeth, Bristol-Myers Squibb, and GlaxoSmithKline, and received speakers' honoraria from Eli Lilly, GlaxoSmithKline, Pfizer, and Wyeth. pump from foremilk to hindmilk from a single breast to determine the excretion gradient and...

The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics

“…11,12 Many antianxiety drugs, antidepressants, and mood stabilizers appear in low concentrations in human milk, with estimated relative infant doses less than 2% of weight-adjusted maternal dose and/or milk-plasma ratios less than 1. 13 However, the percentage of maternal doses that approach clinically significant levels (10% or more) have been reported for bupropion, 14 diazepam, 13 fluoxetine, 15 citalopram, 16 lithium, 17 lamotrigine, 18 and venlafaxine. 19 Data on drug excretion in human milk are not available for up to one-third of psychoactive therapies.…”

Maternal Medication, Drug Use, and Breastfeeding

“…Levels in milk appear quite significant, with RIDs ranging from 9.2% to 18.3%. 22,23 The use of lamotrigine in breastfeeding mothers produces significant plasma levels in some breastfed infants, although they are apparently not high enough to produce side effects. Some investigators suggest it is advisable to monitor the infant's plasma levels if the infant is symptomatic to ensure safety.…”

Normocytic Normochromic Anaemia and Asymptomatic Neutropenia in a 40‐Day‐Old Infant Breastfed by an Epileptic Mother Treated With Lamotrigine: Infant's Adverse Drug Reaction

“…At infant lamotrigine blood levels ranging from 0.6 to 1.8 mg/L, only mild thrombocytosis was observed. 4 Neonates are particularly at risk for high lamotrigine plasma levels due to the immaturity of their glucuronidation capability, required for drug clearance, and because of low plasma protein binding. …”