There are no adequate and well-controlled studies in pregnant women. Lemborexant should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus.
Administration of lemborexant to pregnant rats during organogenesis in 2 separate studies at oral doses of 60, 200, and 600 mg/kg/day or 20, 60, and 200 mg/kg/day resulted in growth delays, embryotoxicity and malformations at the dose of 600 mg/kg/day, which provided maternal plasma exposures that were 388 times the plasma exposure at the maximum recommended human dose (MRHD) based on AUC. The maternal exposure at the no observed adverse effect level (NOAEL) (200mg/kg) was approximately 143 times the exposure at the MRHD based on AUC.
Administration of lemborexant to pregnant rabbits during organogenesis at doses of 10, 30, and 100 mg/kg resulted in a higher incidence of skeletal variations but no embryotoxicity or malformations at a dose of 100 mg/kg/day, which provided exposures approximately 139 times the exposure at the MRHD based on AUC. The exposure at the NOAEL (30 mg/kg) was 23 times the exposure at the MRHD based on AUC.
Oral administration of lemborexant (30, 100, and 300 mg/kg/day) to pregnant rats during gestation and lactation resulted in decreased body weights, femur length, and acoustic startle responses in offspring. The exposure at the NOAEL (100 mg/kg) was 93 times the exposure at the MRHD based on AUC.
In female rats administered lemborexant (oral doses of 30, 100, or 1000 mg/kg/day) prior to and throughout mating and continuing to gestation Day 6, effects on female fertility were observed at doses of 100 and 1000mg/kg/day (approximately 60 and 545 times the exposure at the MRHD based on AUC). Irregular estrous cycle and decreased pregnancy rate were observed at 100 and 1000 mg/kg/day and decreased numbers of corpora lutea, implantations, and live embryos were noted at 1000 mg/kg/ day. The exposure at the NOAEL of 30 mg/kg/day is approximately 12 times the MRHD based on AUC.
Lemborexant did not affect fertility when orally administered to male rats at doses of 30, 100, or 1000 mg/kg/day prior to and throughout mating; the highest dose is approximately 138 times the MRHD based on AUC.
Data from a clinical lactation study show the presence of trace quantities of lemborexant in human milk. The relevant infant dose (RID) is less than 2%of the maximumapproved adult dose of 10mg. A milk-only lactation study was conducted in 8 healthy, adult lactating women. The mean amount of Lemborexant recovered in human milk was 0.0174 mg following a 10 mg maternal dose. The mean calculated daily infant oral dosage was 0.0029 mg/kg/day based on a standardized milk consumption of 150mL/kg/day.
There are no data on the effects of lemborexant on the breastfed infant, or the effects on milk production. Infants exposed to lemborexant through breastmilk should be monitored for excessive sedation. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for lemborexant and any potential adverse effects on the breastfed infant from Lemborexant or from the underlying maternal condition.