There is limited clinical trial experience regarding human overdosage with brexanolone FDA Label. In premarketing clinical studies, two cases of accidental overdosage due to infusion pump malfunction resulted in transient loss of consciousness FDA Label. Both patients regained consciousness approximately 15 minutes after discontinuation of the infusion without supportive measures FDA Label. After full resolution of symptoms, both patients subsequently resumed and completed treatment FDA Label. Overdosage may result in excessive sedation, including loss of consciousness, and the potential for accompanying respiratory changes FDA Label.

There is no available data on brexanolone use in pregnant women to determine a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes FDA Label. However, based on findings from animal studies of other drugs that enhance GABAergic inhibition, brexanolone may cause fetal harm FDA Label.

Available data from a lactation study in 12 women indicate that brexanolone is transferred to breastmilk in nursing mothers FDA Label. However, the relative infant dose (RID) is low, 1% to 2% of the maternal weight-adjusted dosage FDA Label. Also, as brexanolone has low oral bioavailability in adults, infant exposure is expected to be low FDA Label. There were no reports of effects of brexanolone on milk production FDA Label. There are no data on the effects of brexanolone on a breastfed infant FDA Label. Available data on the use of brexanolone during lactation does not suggest a significant risk of adverse reactions to breastfed infants from exposure to brexanolone FDA Label. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for brexanolone and any potential adverse effects on the breastfed child from brexanolone or from the underlying maternal condition FDA Label.

Brexanolone was not genotoxic when tested in an in vitro microbial mutagenicity (Ames) assay, an in vitro micronucleus assay in human peripheral blood lymphocytes, and an in vivo rat bone marrow micronucleus assay FDA Label.

Treatment of female and male rats with brexanolone at doses equal to and greater than 30 mg/kg/day, which is associated with 2 times the plasma levels at the maximum recommended human dose (MRHD) of 90 mcg/kg/hour, caused impairment of female and male fertility and reproduction FDA Label. In female rats, brexanolone was associated with decreased mating and fertility indices, an increase in number of days to mating, prolonged/irregular estrous cycles, an increase in the number of early resorptions, and post implantation loss FDA Label. Reversal of effects in females was observed following a 28-day recovery period FDA Label. In male rats, brexanolone was associated with decreased mating and fertility indices, decreased conception rate, lower prostate, seminal vesicle, and epididymis weight, as well as decreased sperm numbers. Impaired female and male fertility and reproduction were not observed at 0.8 times the MRHD FDA Label.