Remleas Use In Pregnancy & Lactation

Pregnancy: The limited available data on REMLEAS use in pregnant women are insufficient to inform a drug-associated risk. In animal reproductive studies, no malformations were observed when valbenazine was administered orally to rats and rabbits during the period of organogenesis at doses up to 1.8 or 24 times, respectively, the maximum recommended human dose (MRHD) of 80 mg/day based on mg/m² body surface area. However, administration of valbenazine to pregnant rats during organogenesis through lactation produced an increase in the number of stillborn pups and postnatal pup mortalities at doses <1 times the MRHD based on mg/m² [see Animal Data as follows]. Advise a pregnant woman of the potential risk to a fetus.
Animal Data: Valbenazine was administered orally to pregnant rats during the period of organogenesis at 1, 5, and 15 mg/kg/day, which are approximately 0.1, 0.6, and 2 times the MRHD of 80 mg/day based on mg/m² body surface area. Valbenazine produced a significant decrease in maternal body weight gain at 0.6 and 2 times the MRHD of 80 mg/day based on mg/m². No adverse embryo fetal effects were produced when valbenazine was administered at doses up to 2 times the MRHD of 80 mg/day based on mg/m².
Valbenazine was administered orally to pregnant rabbits during the period of organogenesis at 20, 50, and 100 mg/kg/day, which are approximately 5, 12, and 24 times the MRHD of 80 mg/day based on mg/m². No malformations were observed at doses up to 24 times the MRHD of 80 mg/day based on mg/m². However, valbenazine produced a delay in fetal development (decreased fetal weights and delayed ossification) at 24 times the MRHD of 80 mg/day based on mg/m², likely secondary to maternal toxicity (decreased food intake and loss in body weight).
Valbenazine was administered orally to pregnant rats during the period of organogenesis through lactation (day 7 of gestation through day 20 postpartum) at 1, 3, and 10 mg/kg/day, which are approximately 0.1, 0.4, and 1.2 times the MRHD of 80 mg/day based on mg/m². Valbenazine produced an increase in the incidence of stillbirths and postnatal pup mortality at 0.4 and 1.2 times the MRHD of 80 mg/day based on mg/m². Valbenazine did not affect neurobehavioral function including learning and memory and had no effect on sexual maturation at doses <1 times the MRHD of 80 mg/day based on mg/m² (because of death in the majority of the high dose group (1.2 times the MRHD), these parameters were not assessed in this group).
Lactation: There is no information regarding the presence of valbenazine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Valbenazine and its metabolites have been detected in rat milk at concentrations higher than in plasma following oral administration of valbenazine at doses 0.1 to 1.2 times the MRHD based on mg/m². Based on animal findings of increased perinatal mortality in exposed foetuses and pups, advise a woman not to breastfeed during treatment with REMLEAS and for 5 days after the final dose.