Lamotrigine in breast milk and nursing infants: determination of exposure.
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.


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 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.


RESULTS
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.


CONCLUSIONS
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.
Newport
D Jeffrey
DJ
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 1365 Clifton Rd NE, Suite B6100, Atlanta, GA 30322. jeff.newport@emory.edu
Pennell
Page B
PB
Calamaras
Martha R
MR
Ritchie
James C
JC
Newman
Melanee
M
Knight
Bettina
B
Viguera
Adele C
AC
Liporace
Joyce
J
Stowe
Zachary N
ZN
D000328:Adult; D000927:Anticonvulsants / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D001942:Breast Feeding; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D000077213:Lamotrigine; D008895:Milk, Human / Q000737:chemistry*; D014227:Triazines / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*
D000927:Anticonvulsants; D014227:Triazines; D000077213:Lamotrigine