Adverse Reactions (6)]. Avoid coadministration of Qbrexza with other anticholinergic-containingdrugs.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no available data on Qbrexza use in pregnant women to inform a drug-associated riskfor adverse developmental outcomes. In pregnant rats, daily oral administration of

glycopyrrolate (glycopyrronium bromide) during organogenesis did not result in an increasedincidence of gross external or visceral defects [see Data]. When glycopyrrolate was

administered intravenously to pregnant rabbits during organogenesis, no adverse effects onembryo-fetal development were seen. The available data do not support relevant comparisons

of systemic glycopyrronium exposures achieved in the animal studies to exposures observed inhumans after topical use of Qbrexza.

The estimated background risks of major birth defects and miscarriage for the indicatedpopulation are unknown. In the U.S. general population, the estimated background risk of major

birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%,respectively.

Data

Animal Data

Glycopyrrolate was orally administered to pregnant rats at dosages of 50, 200, and400 mg/kg/day during the period of organogenesis. Glycopyrrolate had no effect on maternal

survival, but significantly reduced mean maternal body weight gain over the period of dosing atall dosages eva luated. Mean fetal weight was significantly reduced in the 200 and

400 mg/kg/day dose groups. There were two litters with all resorbed fetuses in the400 mg/kg/day dose group. There were no effects of treatment on the incidence of gross

external or visceral defects. Minor treatment-related skeletal effects included reducedossification of various bones in the 200 and 400 mg/kg/day dose groups; these skeletal effects

were likely secondary to maternal toxicity.

Glycopyrrolate was intravenously administered to pregnant rabbits at dosages of 0.1, 0.5, and1.0 mg/kg/day during the period of organogenesis. Glycopyrrolate did not affect maternal

survival under the conditions of this study. Mean maternal body weight gain and mean foodconsumption over the period of dosing were lower than the corresponding control value in the

0.5 and 1.0 mg/kg/day treatment groups. There were no effects of treatment on fetalparameters, including fetal survival, mean fetal weight, and the incidence of external, visceral, or

skeletal defects. 

Page 5 of 10Female rats that were pregnant or nursing were orally dosed with glycopyrrolate daily atdosages of 0, 50, 200, or 400 mg/kg/day, beginning on day 7 of gestation, and continuing until

day 20 of lactation. Mean body weight of pups in all treatment groups was reduced compared tothe control group during the period of nursing, but eventually recovered to be comparable to the

control group, post-weaning. No other notable delivery or litter parameters were affected bytreatment in any group, including no effects on mean duration of gestation or mean numbers of

live pups per litter. No treatment-related effects on survival or adverse clinical signs wereobserved in pups. 

There were no effects of maternal treatment on behavior, learning, memory,or reproductive function of pups.

8.2 Lactation

Risk Summary