Magnitude of Lamotrigine Exposure Through Breastfeeding.

Importance: Lamotrigine use during breastfeeding has significantly increased in the recent years, whereas breast milk lamotrigine pharmacokinetics data are still sparse. Objectives: To assess lamotrigine exposure in breastfed infants by monitoring maternal serum and breast milk concentrations. Methods: Breastfeeding women treated with lamotrigine were recruited to this study. Maternal trough breast milk and serum samples were collected, and additional breast milk samples were collected 1, 3, 6, 9, 12 hours after lamotrigine consumption. Trough breast milk/serum ratios (M/S ratio) and breast milk area under the curve (AUC) values were calculated. Results: Twenty-one breastfeeding women were recruited to this study, and the final dataset was based on the samples collected from 17 women. Lamotrigine trough serum and mother's milk concentrations were 5.1 ± 3.3 mg/L and 3.1 ± 1.9 mg/L, respectively (mean ± standard deviation). The trough M/S ratio of lamotrigine was 0.66 ± 0.22. The lamotrigine breast milk average AUC was 41.7 ± 24.6 mg·h/L. The estimated infant dose of lamotrigine was 0.52 ± 0.31 mg/kg/day and 0.26 ± 0.15 mg/kg/day for fully and partially breastfed infants, respectively. Significant correlation was found between the maternal lamotrigine serum trough concentrations and the breast milk parameters: trough breast milk concentrations (Spearman's rho = 0.986, p < 0.0001) and breast milk AUC values (Spearman's rho = 0.941, p < 0.0001). No significant correlation was found between the maternal lamotrigine daily dose and serum trough concentrations, breast milk trough concentrations, and breast milk AUC values (Spearman's rho = 0.294, 0.285, and 0.438, p = 0.252, 0.396, and 0.078, respectively). Conclusion and Relevance: High correlation between the maternal lamotrigine trough serum concentrations and the breast milk AUC values was found, implying that monitoring the maternal lamotrigine serum concentrations can be useful for prediction of exposure of infants to lamotrigine through the breast milk. The trial was registered in the Israeli trials registry MOH_2021-09-05_010243 at September 5, 2021 Retrospectively registered https://my.health.gov.il/CliniTrials.

Levetiracetam in lactation: How much is excreted into human breast milk?

AIMS: In breastfeeding women, anti-epileptic therapy can lead to infant toxicities, even with newer anti-epileptic drugs such as levetiracetam. This study assessed levetiracetam breastmilk excretion and its correlation with the maternal oral dose and serum concentrations. METHODS: Women with epilepsy treated with levetiracetam were recruited to this study and completed a questionnaire. Levetiracetam concentrations were determined in serial breastmilk samples (pre-dose to 12 h post-dose period) and in a single pre-dose maternal serum sample. RESULTS: Twenty breastfeeding women and 21 infants (one woman with twins; 16 fully and five partially breastfed infants) participated in this study. The trough breastmilk/serum ratio of levetiracetam was 0.98 ± 0.20. The infant levetiracetam daily dose was 5.39 ± 1.96 and 2.70 ± 0.98 mg. kg-1. d-1 , and the relative infant dose (RID) was 13.8 ± 3.1% and 6.9 ± 1.6% in the fully and partially breastfed infants, respectively. Substantial correlations between the levetiracetam dose, maternal serum and breastmilk trough concentrations, and breastmilk AUC values were found. Three women reported somnolence in their fully breastfed infants, which resolved shortly after switching to partial breastfeeding. All the infants gained weight according to their age. CONCLUSIONS: Infant levetiracetam exposure via the breastmilk was close to the safety thresholds (trough breastmilk/serum ratio slightly below 1, RID > 10% in fully breastfed infants), and infant somnolescence reports could be related to exposure of the infants to levetiracetam via breastmilk. Further studies are warranted to reveal the short- and long-term safety of levetiracetam in breastfeeding.

Therapeutic levetiracetam monitoring during pregnancy: "mind the gap".

BACKGROUND: Epilepsy is one of the most common chronic neurological conditions and its treatment during pregnancy is challenging. Levetiracetam (LEV) is an antiepileptic medication frequently used during pregnancy. Only a few small studies have been published on LEV monitoring during pregnancy, demonstrating decreased serum LEV levels during the first and second trimester; however, the most significant decrease was observed during the third trimester of pregnancy. In this study we aimed to evaluate LEV pharmacokinetics during different stages of pregnancy. METHODS: We followed up and monitored serum levels of pregnant women treated with LEV for epilepsy. RESULTS: Fifty-nine women with 66 pregnancies during the study period were included. The lowest raw LEV serum concentrations were observed during the first trimester. Compared with the pre-pregnancy period, raw serum concentration was lower by 5.76 mg/L [95% confidence interval (CI) (2.78, 8.75), p = 0.039] during the first trimester. Comparing the decrease in the first trimester with either the second or the third, no significant changes were observed (p = 0.945, p = 0.866). Compared with pre-pregnancy measurements, apparent clearance was increased by 71.08 L/day [95%CI (16.34, 125.83), p = 0.011] during the first trimester. About 30% of LEV serum levels during pregnancy were below the laboratory quoted reference range. CONCLUSIONS: Raw LEV serum levels tend to decrease during pregnancy, mainly during the first trimester contrary to previous reports. Monitoring of LEV serum levels is essential upon planning pregnancy and thereafter if pre-pregnancy LEV levels are to be maintained. However, more studies are needed to assess the correlation with clinical outcome.

Correction: Chronic use of psychotropic medications in breastfeeding women: Is it safe?

[This corrects the article DOI: 10.1371/journal.pone.0197196.].

Chronic use of psychotropic medications in breastfeeding women: Is it safe?

BACKGROUND: Current knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant. MATERIALS AND METHODS: In this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11-33) months versus 36 (20-48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics. RESULTS: At follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008). CONCLUSIONS: Chronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.

Safety of Mebendazole Use During Lactation: A Case Series Report.

INTRODUCTION: Mebendazole is an effective drug widely used in the treatment of parasitic infections. Although theoretically considered as safe during lactation, no studies have evaluated its potential adverse effects in infants of breastfeeding mothers. OBJECTIVES: We aimed to evaluate the safety of mebendazole in infants of lactating women treated with the drug. METHODS: Women referred for consultation regarding mebendazole use were invited to participate in the study. Overall 45 lactating women treated with various protocols of mebendazole were recruited in this case series study. RESULTS: Regardless of the treatment protocol used (single or repeated doses) mebendazole was well tolerated and was not associated with any adverse effects in infants of lactating mothers. There was mild GI irritability in two treated women. CONCLUSION: This study provides first evidence in humans as to the safety of mebendazole in breastfeeding.