Glycopyrronium Drug Information

Qbrexza is indicated for topical treatment of primary axillary hyperhidrosis in adult and pediatric patients 9 years of age and older. Qbrexza is an anticholinergic indicated for topical treatment of primary axillary hyperhidrosis in adults and pediatric patients 9 years of age and older.

For topical use only. Qbrexza is for topical use in the underarm area only and not for use in other body areas. Qbrexza is administered by a single-use pre-moistened cloth packaged in individual pouches.

Qbrexza should be applied to clean dry skin on the underarm areas only. Qbrexza should not be used more frequently than once every 24 hours. Tear open the pouch and pull out the cloth, unfold the cloth, and wipe it across one entire underarm once.

Using the same cloth, wipe the other underarm once. A single cloth should be used to apply Qbrexza to both underarms. After applying Qbrexza, discard the cloth in the household trash out of reach of children and others.

Wash hands immediately with soap and water after applying and discarding the Qbrexza cloth. Qbrexza may cause temporary dilation of the pupils and blurred vision if it comes in contact with the eyes. Avoid transfer of Qbrexza to the periocular area . Do not apply Qbrexza to broken skin.

Avoid using Qbrexza with occlusive dressings. For topical use only. Apply Qbrexza once daily to both axillae using a single cloth.

• The following adverse reactions are described in greater detail in other sections
• New or Worsening Urinary Retention [see Warnings and Precautions ( 5.1 )] Most common adverse reactions (incidence ≥2%) are dry mouth, mydriasis, oropharyngeal pain, headache, urinary hesitation, vision blurred, nasal dryness, dry throat, dry eye, dry skin, constipation. Local skin reactions, including erythema, burning/stinging and pruritus were also common (>5%) ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Journey Medical Corp. at 1-855-531-1859 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two double-blind, vehicle-controlled clinical trials (Trial 1 [NCT02530281] and Trial 2 [NCT02530294]) of 459 subjects treated with Qbrexza once daily and 232 treated with vehicle, subjects were 9 to 76 years of age, 47% male, and the percentages of White, Black (including African Americans), and Asian subjects were 82%, 12%, and 1%, respectively. Table 1 summarizes the most frequent adverse reactions (≥2%) in subjects with primary axillary hyperhidrosis treated with Qbrexza. Table 1: Adverse Reactions Occurring in ≥2% of Subjects Adverse Reactions Qbrexza (N=459) n (%) Vehicle (N=232) n (%) Dry mouth 111 (24.2%) 13 (5.6%) Mydriasis 31 (6.8%) 0 Oropharyngeal pain 26 (5.7%) 3 (1.3%) Headache 23 (5.0%) 5 (2.2%) Urinary hesitation 16 (3.5%) 0 Vision blurred 16 (3.5%) 0 Nasal dryness 12 (2.6%) 1 (0.4%) Dry throat 12 (2.6%) 0 Dry eye 11 (2.4%) 1 (0.4%) Dry skin 10 (2.2%) 0 Constipation 9 (2.0%) 0 Table 2 shows the most frequently reported local skin reactions, which were relatively common in both the Qbrexza and vehicle groups. Table 2: Local Skin Reactions a Patients with a post-baseline local skin reaction assessment Local Skin Reactions Qbrexza (N=454) a n (%) Vehicle (N=231) a n (%) Erythema 77 (17.0%) 39 (16.9%) Burning/stinging 64 (14.1%) 39 (16.9%) Pruritus 37 (8.1%) 14 (6.1%) In an open-label safety trial (NCT02553798), 564 subjects were treated for up to an additional 44 weeks after completing Trial 1 or Trial 2. Adverse reactions occurring at a frequency ≥2.0% were: dry mouth (16.9%), vision blurred (6.7%), nasopharyngitis (5.8%), mydriasis (5.3%), urinary hesitation (4.2%), nasal dryness (3.6%), dry eye (2.9%), pharyngitis (2.2%), and application site reactions (pain [6.4%], dermatitis [3.8%], pruritus [3.8%], rash [3.8%], erythema [2.4%]). 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of Qbrexza. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Qbrexza exposure.
• Genitourinary system disorders : new onset urinary retention [ see Warnings and Precautions ( 5.1 ) ]

Anticholinergics Coadministration of Qbrexza with anticholinergic medications may result in additive interaction

leading to an increase in anticholinergic adverse effects . Avoid coadministration of Qbrexza with other anticholinergic-containing drugs.

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 . 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.

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 . 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 . The safety and effectiveness of Qbrexza have not been established in pediatric patients under 9 years of age.

Qbrexza is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of Qbrexza (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome). Qbrexza is contraindicated in patients with medical conditions that can be exacerbated by the anticholinergic effect of Qbrexza (e.g., glaucoma, paralytic ileus, unstable cardiovascular status in acute hemorrhage, severe ulcerative colitis, toxic megacolon complicating ulcerative colitis, myasthenia gravis, Sjogren’s syndrome).

Because glycopyrronium is a quaternary amine which does not easily cross the blood-brain barrier, symptoms of glycopyrronium overdosage are generally more peripheral in nature rather than central compared to other anticholinergic agents. Associated signs and symptoms related to excessive anticholinergic activity may include flushing, hyperthermia, tachycardia, ileus, urinary retention, loss of ocular accommodation and light sensitivity due to mydriasis. In the case of overdose when symptoms are severe or life threatening, therapy may include: Managing per standard of care any acute conditions such as hyperthermia, coma, and/or seizures, as applicable, and managing any myoclonic or choreoathetoid movements which may lead to rhabdomyolysis in some cases of anticholinergic overdosage Managing severe urinary retention with catheterization if not spontaneously reversed within several hours Providing cardiovascular support and/or controlling arrhythmias Maintaining an open airway, providing ventilation as necessary Administering a quaternary ammonium anticholinesterase such as neostigmine to help alleviate severe and/or life threatening peripheral anticholinergic effects.

Topical overdosing of Qbrexza could result in an increased incidence or severity of local skin reactions. Administration of Qbrexza under occlusive conditions may result in an increase in anticholinergic effects, including dry mouth and urinary hesitation.