Dayvigo Use In Pregnancy & Lactation

Pregnancy: Risk Summary: There are no available data on DAYVIGO use in pregnant women to evaluate for drug-associated risks of major birth defects, miscarriage or adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of lemborexant to pregnant rats and rabbits during the period of organogenesis caused toxicities only at high multiples of the human exposure at the maximum recommended human dose (MRHD) based on AUC. The no observed adverse effect levels (NOAEL) are approximately >100 and 23 times the MRHD based on AUC in rats and rabbits, respectively. Similarly, oral administration of lemborexant to pregnant and lactating rats caused toxicities only at high multiples of the human exposure at the MRHD based on AUC. The NOAEL is 93 times the MRHD based on AUC [see Data as follows].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.
Data: Animal Data: Lemborexant was administered orally to pregnant rats during the period of organogenesis in 2 studies at doses of 60, 200, and 600 mg/kg/day or 20, 60, and 200 mg/kg/day, which are approximately 6 to >300 times the MRHD based on AUC. Lemborexant caused maternal toxicity, manifested by decreased body weight and food consumption, decreased mean fetal body weight, an increased number of dead fetuses, and skeletal, external and visceral malformations (omphalocele, cleft palate, and membranous ventricular septal defect) at >300 times the MRHD based on AUC. The NOAEL of 200 mg/kg/day is approximately 143 times the MRHD based on AUC.
Lemborexant was administered orally to pregnant rabbits during the period of organogenesis at doses of 10, 30, and 100 mg/kg/day, which are approximately 7 to 139 times the MRHD based on AUC. Lemborexant caused maternal toxicity that consisted of decreased body weight and food consumption and a higher incidence of skeletal variations (presence of cervical ribs and supernumerary lung lobes) at approximately 139 times the MRHD based on AUC. The NOAEL of 30 mg/kg/day is approximately 23 times the MRHD based on AUC.
Lemborexant was administered orally to pregnant rats during pregnancy and lactation at doses of 30, 100, and 300 mg/kg/day, which are approximately 15 to 206 times the MRHD based on AUC. Lemborexant caused maternal toxicity that consisted of decreased body weight and food consumption and toxicity to offspring consisting of decreased pup body weights, decreased femur length, and decreased acoustic startle responses at 206 times the MRHD based on AUC. The NOAEL of 100 mg/kg/day is approximately 93 times the MRHD based on AUC.
Lactation: Risk Summary: There are no data on the presence of lemborexant in human milk, the effects on the breastfed infant, or the effects on milk production. Lemborexant and its metabolites are present in the milk of lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Infants exposed to DAYVIGO through breastmilk should be monitored for excessive sedation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DAYVIGO and any potential adverse effects on the breastfed infant from DAYVIGO or from the underlying maternal condition.