O31 Levetiracetam monitoring in breast-milk: high inter-individual variability

Abstract

BackgroundAnti-epileptic drug therapy is a great challenge for the practitioners during pregnancy and lactation. Levetiracetam (LEV) is commonly prescribed to pregnant women, however, there are only few publications on its use during lactation with small number of participants.ObjectiveTo monitor LEV levels in breast-milk of epileptic mothers treated with LEV.MethodsBreastfeeding women treated with LEV during pregnancy and after delivery were recruited. Milk sample was collected before administration of the drug and other samples were collected at time points of 1,3,6,9, and 12 hours after drug administration. Breastmilk and blood LEV levels were measured using HPLC.ResultsFourteen breastfeeding women participated in the study: 9 infants were fully breastfed whereas 5 were partially breastfed. Maternal average daily dose of LEV was 2517 mg. Average infant´s age was 8 weeks (3–22w). Average infant´s weight 4368 gr (3300–7000 gr). Milk/Plasma LEV concentration ratio was 0.88 (0.23–1.1). Relative Infant Dose (RID) was 40% in partial breast feeding, and 61% in full breastfeeding. Estimated average daily dose that all infants received through milk was 158 mg/d (83–250 mg). The normalized dose for the average infant weight per day was 36 mg, which is 15% less than the maximal daily dose of LEV in infants (max. daily dose in infants 1–6 months in 42 mg/d). No adverse reactions were observed in the breastfeed infants.ConclusionsAlthough the RID of LEV were found to be high, no adverse reactions were observed in the infants; Nevertheless, further studies are needed to elucidate the high variability of LEV excretion into breastmilk.Disclosure(s)Nothing to disclose

Umbilical Cord, Maternal Milk, and Breastfed Infant Levetiracetam Concentrations Monitoring at Delivery and during Early Postpartum Period

“…During breastfeeding, we observed a similar result of the milk/maternal serum concentration ratio both in colostrum and mature milk as in the previous reports of Tomson et al, Johannessen et al, and Dinavitser et al [ 4 , 7 , 8 , 9 ]. We did not confirm the considerable accumulation of LEV in breast milk reported by Kramer et al [ 13 ].…”

“…In our study, especially the number of simultaneously analyzed maternal serum, milk and infant serum concentrations were greater (from one center using a consistent methodology) than in all previous studies using varying and incomparable criteria [4,[7][8][9][10][11][12][13][14][15][16][17], see Table 5. The mean umbilical cord/maternal serum concentration ratio was 1.10, and paired maternal and umbilical cord serum concentrations were not significantly different.…”

“…Breastfed infant exposure to ASM in milk varies, depending on multiple factors: maternal serum drug concentration, the milk/maternal serum concentration ratio, the milk volume ingested by infant, and the absorption, metabolism, and excretion of the drug in the infant [ 22 ]. The elimination half-life of plasma LEV was reported 16–18 h in both nursed and formula-fed infants [ 4 , 9 ], which is longer than the 6–8 h found in adults [ 19 ]. Conversely, the clearance of LEV in neonates was found higher than predicted and increased significantly during the first week of life into the range seen in older children and exceeded values reported in adults.…”

“…However, the effects of pregnancy on LEV disposition vary considerably between individuals and monitoring of LEV levels during pregnancy and after delivery is recommended [ 5 , 6 ]. An extensive transfer of LEV from mother to fetus and into breast milk was reported by some authors in small study groups or case-reports [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. Despite this, breastfed infants had measured insignificant serum concentrations, and LEV is usually considered compatible with breastfeeding [ 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”