Qbrexza

Pregnancy

Risk Summary

There are no available data on Qbrexza use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. In pregnant rats, daily oral administration of glycopyrrolate (glycopyrronium bromide) during organogenesis did not result in an increased incidence of gross external or visceral defects [see Data]. When glycopyrrolate was administered intravenously to pregnant rabbits during organogenesis, no adverse effects on embryo-fetal development were seen. The available data do not support relevant comparisons of systemic glycopyrronium exposures achieved in the animal studies to exposures observed in humans after topical use of Qbrexza.

The estimated background risks of major birth defects and miscarriage for the indicated population 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, and 400 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 at all dosages evaluated. 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 the 400 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 reduced ossification 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, and 1.0 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 food consumption 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 fetal parameters, including fetal survival, mean fetal weight, and the incidence of external, visceral, or skeletal defects.

Female rats that were pregnant or nursing were orally dosed with glycopyrrolate daily at dosages 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 to the 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 by treatment 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 were observed in pups. There were no effects of maternal treatment on behavior, learning, memory, or reproductive function of pups.

Lactation

Risk Summary

There are no data on the presence of glycopyrrolate or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Qbrexza and any potential adverse effects on the breastfed infant from Qbrexza or from the underlying maternal condition.

Pediatric Use

The safety, effectiveness and pharmacokinetics of Qbrexza have been established in pediatric patients age 9 years and older for topical treatment of primary axillary hyperhidrosis [see Clinical Pharmacology ]. Use of Qbrexza in this age group is supported by evidence from two multicenter, randomized, double-blind, parallel-group, vehicle-controlled 4-week trials which included 34 pediatric subjects 9 years and older [see Adverse Reactions and Clinical Studies ]. The safety and effectiveness of Qbrexza have not been established in pediatric patients under 9 years of age.

Geriatric Use

Clinical trials of Qbrexza did not include sufficient numbers of subjects age 65 years and older to determine whether they respond differently from younger subjects.

Renal Impairment

The elimination of glycopyrronium is severely impaired in patients with renal failure [see Clinical Pharmacology ].

New or Worsening Urinary Retention

New or worsening signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder) have occurred in patients taking Qbrexza with or without a history of documented urinary retention. Instruct patients to discontinue use immediately and consult a physician should any of these signs or symptoms develop.

Qbrexza should be used with caution in patients with prostatic hypertrophy or bladder-neck obstruction.

Control of Body Temperature

In the presence of high ambient temperature, heat illness (hyperpyrexia and heat stroke due to decreased sweating) can occur with the use of anticholinergic drugs such as Qbrexza. Advise patients using Qbrexza to watch for generalized lack of sweating when in hot or very warm environmental temperatures and to avoid use if not sweating under these conditions.

Operating Machinery or an Automobile

Transient blurred vision may occur with use of Qbrexza. If blurred vision occurs, the patient should discontinue use until symptoms resolve. Patients should be warned not to engage in activities that require clear vision such as operating a motor vehicle or other machinery, or performing hazardous work until the symptoms have resolved.

Risk of Accidental Exposure

Cases of accidental exposure resulting in mydriasis, anisocoria, and blurred vision have been reported in postmarketing surveillance of Qbrexza. The exposures occurred when children accessed Qbrexza wipes discarded in trash or when patients touched the periocular area after using Qbrexza. In most cases, the mydriasis, anisocoria, and blurred vision were temporary and resolved within one week following exposure. The risk of accidental exposure was increased in these cases by not adhering to recommendations for the appropriate use of Qbrexza.

Strict adherence to the recommended hand washing after use and disposal instructions is of the utmost importance to prevent accidental exposure. [see Dosage and Administration (2)].