Presence of Hypnotics in the Cord Blood and Breast Milk, with No Adverse Effects in the Infant: A Case Report.

Background: Hypnotics are frequently used for insomnia in pregnant and lactating women. This case study assessed zolpidem concentrations in the cord blood and breast milk and ramelteon concentrations in the breast milk of a woman who was treated with zolpidem and ramelteon for insomnia. Materials and Methods: Zolpidem concentrations were measured in maternal serum, breast milk, and cord blood. Concentrations of ramelteon and M-II, an active ramelteon metabolite, were measured in maternal serum and breast milk. Case Report: A 46-year-old female patient diagnosed with insomnia received 5-10 mg/day zolpidem during pregnancy and lactation and 8 mg/day ramelteon during lactation. A male infant weighing 3,329 g was born at 38 weeks' gestation, with no congenital abnormalities found during pregnancy or at birth. The infant was normal at the 1-month postpartum checkup. The maternal/placental ratio of zolpidem concentrations was 0.1 at 7.4 hours after maternal dosing, similar to that reported in previous studies. The calculated relative infant dose through breast milk based on the maximum drug concentration in breast milk at 2.2 hours after maternal dosing was 2.7% for zolpidem and 0.2% for ramelteon. Ramelteon and its metabolite (M-II) concentrations in the breast milk were equivalent to those in the maternal serum, although the infant exposure of these drugs was low for an oral dose. Conclusions: In the current case, zolpidem transferred into the placenta and breast milk, and ramelteon transferred into the breast milk. Further studies should assess the safety of zolpidem and ramelteon in fetus and breastfed infants.

Brotizolam During Pregnancy and Lactation: Brotizolam Levels in Maternal Serum, Cord Blood, Breast Milk, and Neonatal Serum.

Background: Brotizolam is a sedative-hypnotic thienotriazolodiazepine that is a benzodiazepine analog used for debilitating insomnia. Anxiety, depression, and sleep disorders occur in about 15% of pregnant and lactating women; however, no studies have examined brotizolam transfer across the placenta or its excretion into breast milk. In this case report, we assessed brotizolam concentrations in maternal and neonatal blood, cord blood, and breast milk. Materials and Methods: Brotizolam concentrations in maternal serum, breast milk, cord blood, and neonatal serum were measured while the mother was taking oral brotizolam 0.25 mg once daily. Case Report: A 28-year-old woman diagnosed with bipolar II disorder received brotizolam during pregnancy (28-40 weeks' gestational age) and lactation, along with sertraline, alprazolam, and trazodone. A male infant weighing 3,412 g was born at 40 weeks of gestation. Neonatal abstinence syndrome manifested as fever, limb tremor, and central cyanosis, requiring oxygenation and intravenous phenobarbital administration for 4 days. No pulmonary dysfunction or birth defects were detected. Brotizolam concentrations in maternal serum at 7.0 and 14.0 hours after maternal dosing were 0.51 and 0.22 ng/mL, respectively. Brotizolam was not detected in cord blood or infant serum 9.2 hours after maternal dosing. The brotizolam concentration in breast milk collected 7.1 hours after maternal dosing was 0.12 ng/mL. The infant developed normally, with no drug-related adverse effects at the 1-, 3-, or 6-month postpartum checkups. Conclusion: Brotizolam transfer into placenta and breast milk was negligible. Further studies should assess the safety of brotizolam in fetuses and breastfed infants.