Qbrexza

Name: Qbrexza

Indications and Usage for Qbrexza

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

Contraindications

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).

Warnings and Precautions

Worsening of Urinary Retention

Qbrexza should be used with caution in patients with a history or presence of documented urinary retention. Prescribers and patients should be alert for signs and symptoms of urinary retention (e.g., difficulty passing urine, distended bladder), especially in patients with prostatic hypertrophy or bladder-neck obstruction. Instruct patients to discontinue use immediately and consult a physician should any of these signs or symptoms develop.

Patients with a history of urinary retention were not included in the clinical studies.

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.

Qbrexza - Clinical Pharmacology

Mechanism of Action

Glycopyrronium is a competitive inhibitor of acetylcholine receptors that are located on certain peripheral tissues, including sweat glands. In hyperhidrosis, glycopyrronium inhibits the action of acetylcholine on sweat glands, reducing sweating.

Pharmacodynamics

The pharmacodynamics of Qbrexza are not known.

Pharmacokinetics

Absorption

The pharmacokinetics of glycopyrronium were evaluated in adult and pediatric patients with primary axillary hyperhidrosis following Qbrexza once daily applied to the axillae for 5 days. The mean ± SD exposures of glycopyrronium are presented in Tables 3 and 4. There was no evidence of accumulation.

Table 3: Mean ± SD Plasma Exposures of Glycopyrronium in Adults Following Qbrexza Once Daily for 5 days
Abbreviations: Maximum concentration (Cmax), Area under the time concentration curve
(AUC) between 0 and 6 hours following administration of Qbrexza (AU0-6h), AUC between
0 and 24 hours following administration of Qbrexza (AUC0-24h)
Parameter Adult Patients
Cmax (ng/mL) 0.08 ± 0.04
AUC0-6h (h∗ng/mL) 0.2 ± 0.14
AUC0-24h (h∗ng/mL) 0.88 ± 0.57
Median Tmax (Range) (h) 1 (0, 10)

Distribution

After IV administration, glycopyrronium has a mean volume of distribution in children aged 1 to 14 years of approximately 1.3 to 1.8 L/kg, with a range from 0.7 to 3.9 L/kg. In adults aged 60-75 years, the volume of distribution was lower (0.42 L/kg ± 0.22).

Elimination

Metabolism

A small proportion of glycopyrronium is metabolized following IV administration. The metabolic pathway for glycopyrronium is not characterized.

Excretion

Following administration of a single radiolabeled IV glycopyrronium dose to adult subjects who underwent surgery for cholelithiasis, approximately 85% of total radioactivity was excreted in urine and < 5% was present in bile drainage. Greater than 80% of the radioactivity in both urine and bile was unchanged drug.

Specific Populations

The pharmacokinetics of glycopyrronium were not evaluated in pregnant women or patients with hepatic impairment.

Pediatric Subjects

The mean ± SD exposures of glycopyrronium in pediatric subjects following Qbrexza once daily for 5 days are presented in Table 4. There was no evidence of accumulation.

Table 4: Mean ± SD Plasma Exposures of Glycopyrronium in Pediatric Subjects Aged 10 to 17 years Following Qbrexza Once Daily for 5 days
Parameter Pediatric Patients
Cmax (ng/mL) 0.07 ± 0.06
AUC0-6h (h∗ng/mL) 0.18 ± 0.13
AUC0-24h (h∗ng/mL) Not calculated
Median Tmax (Range) (h) 1.5 (0, 6)

Patients with Renal Impairment

Following a 4 mcg/kg IV dose of a glycopyrronium formulation for IV use, mean glycopyrronium AUC (10.6 mcg·h/L), CL (0.43 L/h/kg) and 3-hour urinary excretion (0.7%) were significantly different in uremic subjects undergoing renal transplantation surgery than those of healthy subjects (3.73 mcg·h/L, 1.14 L/h/kg, and 50%, respectively).

Pharmacokinetics of Qbrexza in subjects with renal impairment has not been studied.

In Vitro Studies

In vitro studies indicated that under the conditions of clinical use, Qbrexza is not expected to induce cytochrome P450 (CYP) enzymes 1A2, 2B6 and 3A4; or inhibit 1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Glycopyrronium tosylate was not carcinogenic when topically applied to rats daily for up to 24 months in solution at concentrations of 1%, 2%, and 4% w/w.

When glycopyrrolate was administered via oral gavage to mice for up to 24 months at dosages of 2.5, 7, and 20 mg/kg/day in both genders, no significant changes in tumor incidence were observed when compared to control.

When glycopyrrolate was administered via oral gavage to rats for up to 24 months at dosages of 5, 15, and 40 mg/kg/day in both genders, no significant changes in tumor incidence were observed when compared to control.

Glycopyrrolate was negative in a battery of genetic toxicology studies that included a bacterial reverse mutation (Ames) assay, a mouse lymphoma assay conducted with L5178Y/TK+/- cells, and an in vivo micronucleus assay with mice. Glycopyrronium tosylate was negative in an Ames assay.

Glycopyrrolate was assessed for effects on fertility or general reproductive function in rats. Rats of both genders received glycopyrrolate at dosages up to 100 mg/kg/day via oral gavage. No treatment-related effects on fertility or reproductive parameters were observed in either gender.

How Supplied/Storage and Handling

How Supplied

Qbrexza is supplied as:

A single-use cloth pre-moistened with a 2.4% glycopyrronium solution in a pouch

Carton of 30 pouches      NDC 70428-011-12

Storage and Handling

Store at room temperature 20° - 25°C (68° - 77°F); excursions permitted to 15° - 30°C (59° - 86°F) [See USP Controlled Room Temperature].

Qbrexza is flammable; keep away from heat or flame.

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