GELNIQUE

6 ADVERSE REACTIONS 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 trial of another drug and may not reflect the rates observed in practice. The most common adverse reactions (incidence > 5% and > placebo) were dry mouth, urinary tract infection, and application site reactions. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 or contact the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience The safety of GELNIQUE was evaluated in 789 patients (389 randomized to GELNIQUE 1 g and 400 randomized to placebo) during a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study. A subset of these 789 patients (N = 216) participated in the 14-week open-label safety extension that followed the placebo-controlled study. Of 216 patients in the safety extension, 107 were randomized to placebo gel during the double-blind, placebo-controlled 12-week study. In the combined double-blind, placebo-controlled study and the open-label safety extension, a total of 496 patients were exposed to at least one dose of GELNIQUE. Four hundred thirty-one (431) patients received at least 12 weeks of GELNIQUE treatment and 85 patients received 26 weeks of GELNIQUE treatment. The study population primarily consisted of Caucasian women (approximately 90%) with an average age of 59 years who had overactive bladder with urge urinary incontinence. Table 1 lists adverse reactions that were reported in the randomized, double-blind, placebo-controlled 12-week study in greater than 2% of patients treated with GELNIQUE and at an incidence greater than placebo. Table 1: Common Adverse Reactions in the Randomized, Double-blind, Placebo-controlled 12-Week Study (> 2% and > placebo) Adverse Reaction GELNIQUE 1 gram N = 389 n (%) Placebo N = 400 n (%) Dry mouth 29 (7.5) 11 (2.8) Urinary tract infection 27 (6.9) 17 (4.3) Application site reactions* 21 (5.4) 4 (1.0) Upper respiratory tract infection 21 (5.4) 20 (5.0) Dizziness 11 (2.8) 4 (1.0) Nasopharyngitis 11 (2.8) 9 (2.3) Fatigue 8 (2.1) 4 (1.0) Gastroenteritis viral 8 (2.1) 7 (1.8) * Includes application site pruritus, dermatitis, papules, anesthesia, erythema, irritation, pain and papules Other common adverse reactions that were reported in ≥ 1% of GELNIQUE-treated patients were headache (1.5%), constipation (1.3%), and pruritus (1.3%). Application site pruritus (2.1%) and application site dermatitis (1.8%) were the most commonly reported application site reactions. A majority of adverse reactions were described as mild or moderate in intensity, except for two patients reporting severe headache. The most common adverse reaction leading to drug discontinuation was application site reaction (0.8% with GELNIQUE versus 0.3% with placebo). The most common adverse reactions reported during the 14-week open-label extension study were application site reactions (6.0%) and dry mouth (1.9%). The most common reason for premature discontinuation was application site reactions (9 patients or 4.2%). Two of these 9 patients experienced application site reactions of severe intensity (dermatitis, urticaria, and erythema). 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of GELNIQUE. Because these 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 drug exposure. Nervous System Disorders: Memory impairment, dizziness, somnolence, confusion Psychiatric Disorders: Delirium, hallucinations

4 CONTRAINDICATIONS The use of GELNIQUE is contraindicated in the following conditions: Urinary retention Gastric retention Uncontrolled narrow-angle glaucoma Known serious hypersensitivity reaction to GELNIQUE, oxybutynin, or to any of the components of GELNIQUE [ see Warnings and Precautions (5.3 , 5.4) ] . Urinary retention ( 4 ) Gastric retention ( 4 ) Uncontrolled narrow-angle glaucoma ( 4 ) Known serious hypersensitivity reaction to GELNIQUE, oxybutynin, or to any of the components of GELNIQUE ( 4 )

11 DESCRIPTION Oxybutynin is an antispasmodic, antimuscarinic agent. GELNIQUE (oxybutynin chloride) is a clear and colorless hydroalcoholic gel containing 100 mg oxybutynin chloride per gram of gel. GELNIQUE is available in a metered-dose pump that dispenses 30 metered 1 gram doses or in a 1 gram (1.14 mL) unit dose. Each dose contains 100 mg oxybutynin chloride. Oxybutynin is delivered as a racemate of R- and S- isomers. Chemically, oxybutynin chloride is d, l (racemic) 4-(Diethylamino)-2-butynyl (±)-α-phenylcyclohexaneglycolate hydrochloride. The empirical formula of oxybutynin is C 22 H 31 NO 3 • HCl. Its structural formula is: Oxybutynin chloride is a white powder with a molecular weight of 393.95. Inactive ingredients in GELNIQUE are alcohol, USP; glycerin, USP; hydroxypropyl cellulose, NF; sodium hydroxide, NF; and purified water, USP. structural formula

2 DOSAGE AND ADMINISTRATION The contents of one sachet or one actuation of the metered-dose pump of GELNIQUE should be applied once daily to dry, intact skin on the abdomen, upper arms/shoulders, or thighs. Application sites should be rotated. Application of GELNIQUE should not be made to the same site on consecutive days [ see Clinical Pharmacology (12.3) ] . GELNIQUE is for topical application only and should not be ingested. Apply contents of one sachet or one actuation of the metered-dose pump of GELNIQUE once daily to dry, intact skin on the abdomen, upper arms/shoulders, or thighs. ( 2 ) Rotate application sites, avoiding use of the same site on consecutive days. ( 2 ) GELNIQUE is for topical application only and should not be ingested. ( 2 )

1 INDICATIONS AND USAGE GELNIQUE is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency [ see Clinical Studies (14) ] . GELNIQUE is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. ( 1 )

10 OVERDOSAGE Overdosage with oxybutynin has been associated with anticholinergic effects including central nervous system excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention. Oral ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old boy who experienced memory loss, and in a 34-year-old woman who developed stupor, followed by disorientation and agitation on awakening, dilated pupils, dry skin, cardiac arrhythmia, and retention of urine. Both patients recovered fully with symptomatic treatment. Plasma concentrations of oxybutynin begin to decline 24 hours after GELNIQUE application. If overexposure occurs, monitor patients until symptoms resolve.

7 DRUG INTERACTIONS No specific drug-drug interaction studies have been performed with GELNIQUE. Other Anticholinergics (muscarinic antagonists): Concomitant use with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision and other anticholinergic pharmacological effects. ( 7.1 ) 7.1 Other Anticholinergics The concomitant use of GELNIQUE with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision, somnolence and other anticholinergic pharmacological effects. 7.2 Cytochrome P450 Inhibitors Pharmacokinetic studies have not been performed with patients concomitantly receiving cytochrome P450 enzyme inhibitors, such as antimycotic agents (e.g., ketoconazole, itraconazole, and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin).

12 CLINICAL PHARMACOLOGY Figure 1 12.1 Mechanism of Action Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. Oxybutynin is a racemic (50:50) mixture of R- and S- isomers. Antimuscarinic activity resides predominantly with the R- isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin in in vitro studies. 12.3 Pharmacokinetics Absorption Oxybutynin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 7 days of continuous dosing. Absorption of oxybutynin is similar when GELNIQUE is applied to the abdomen, upper arm/shoulders or thighs. Mean plasma concentrations during a randomized, crossover study of the three recommended application sites in 39 healthy men and women are shown in Figure 1. Average steady-state plasma oxybutynin concentrations were 4.7, 5.2, and 5.5 ng/mL for the abdomen, upper arm/shoulder and thigh application sites, respectively (Table 2). Table 2: Mean (SD) steady-state pharmacokinetic parameters for oxybutynin following GELNIQUE application to the abdomen, upper arm/shoulder and thigh (N = 39). Application Site AUC 0-24 (ng•hr/mL) C max (ng/mL) C avg (ng/mL) Abdomen 112.7 (58.00) 6.8 (3.93) 4.7 (2.39) Upper Arm/Shoulder 133.8 (81.58) 8.3 (5.97) 5.5 (3.37) Thigh 125.1 (84.67) 7.0 (4.95) 5.2 (3.50) Distribution Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated to be 193 L after intravenous administration of 5 mg oxybutynin chloride. Metabolism Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin (DEO), which is pharmacologically active. Transdermal administration of oxybutynin bypasses the first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyloxybutynin metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The AUC ratio of N-desethyloxybutynin metabolite to parent compound following multiple transdermal applications is approximately 1:1 for GELNIQUE. Following intravenous administration, the elimination half-life of oxybutynin is approximately 2 hours. After the final steady-state dose of GELNIQUE, oxybutynin and N-desethyloxybutynin demonstrated biphasic elimination with plasma concentrations beginning to decrease 24 hours after dosing. Elimination was more rapid between 24 and 48 hours after dosing, during which time plasma concentrations of oxybutynin and N-desethyloxybutynin declined by about one-half. This rapid elimination phase was followed by a more prolonged terminal elimination phase. The apparent elimination half-lives including the terminal elimination phase were 64 hours and 82 hours for oxybutynin and DEO, respectively. Excretion Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin. Person-to-Person Transference The potential for dermal transfer of oxybutynin from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with GELNIQUE engaged in vigorous contact with an untreated partner for 15 minutes, either with (N = 14 couples) or without (N = 12 couples) clothing covering the application area. The untreated partners not protected by clothing demonstrated detectable plasma concentrations of oxybutynin (mean C max = 0.94 ng/mL). Two of the 14 untreated subjects participating in the clothing-to-skin contact regimen had measurable oxybutynin plasma concentrations (C max ≤ 0.1 ng/mL) during the 48 hours following contact with treated subjects; oxybutynin was not detectable with the remaining 12 untreated subjects. Use of Sunscreen The effect of sunscreen on the absorption of oxybutynin when applied 30 minutes before or 30 minutes after GELNIQUE application was evaluated in a single-dose randomized crossover study (N = 16). Concomitant application of sunscreen, either before or after GELNIQUE application, had no effect on the systemic exposure of oxybutynin. Showering The effect of showering on the absorption of oxybutynin was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after GELNIQUE application (N = 20). The results of the study indicate that showering after one hour does not affect the overall systemic exposure to oxybutynin. Race The effect of race on the pharmacokinetics of GELNIQUE has not been studied. Specific Populations: Geriatric: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on geriatric status in patients following administration of GELNIQUE [see Use in Specific Populations (8.5) ]. Pediatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin have not been evaluated in individuals younger than 18 years of age [see Use in Specific Populations (8.4) ] . Gender: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on gender in healthy volunteers following administration of GELNIQUE.

12.1 Mechanism of Action Oxybutynin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. Oxybutynin is a racemic (50:50) mixture of R- and S- isomers. Antimuscarinic activity resides predominantly with the R- isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of oxybutynin in in vitro studies.

12.3 Pharmacokinetics Absorption Oxybutynin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 7 days of continuous dosing. Absorption of oxybutynin is similar when GELNIQUE is applied to the abdomen, upper arm/shoulders or thighs. Mean plasma concentrations during a randomized, crossover study of the three recommended application sites in 39 healthy men and women are shown in Figure 1. Average steady-state plasma oxybutynin concentrations were 4.7, 5.2, and 5.5 ng/mL for the abdomen, upper arm/shoulder and thigh application sites, respectively (Table 2). Table 2: Mean (SD) steady-state pharmacokinetic parameters for oxybutynin following GELNIQUE application to the abdomen, upper arm/shoulder and thigh (N = 39). Application Site AUC 0-24 (ng•hr/mL) C max (ng/mL) C avg (ng/mL) Abdomen 112.7 (58.00) 6.8 (3.93) 4.7 (2.39) Upper Arm/Shoulder 133.8 (81.58) 8.3 (5.97) 5.5 (3.37) Thigh 125.1 (84.67) 7.0 (4.95) 5.2 (3.50) Distribution Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated to be 193 L after intravenous administration of 5 mg oxybutynin chloride. Metabolism Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin (DEO), which is pharmacologically active. Transdermal administration of oxybutynin bypasses the first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyloxybutynin metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The AUC ratio of N-desethyloxybutynin metabolite to parent compound following multiple transdermal applications is approximately 1:1 for GELNIQUE. Following intravenous administration, the elimination half-life of oxybutynin is approximately 2 hours. After the final steady-state dose of GELNIQUE, oxybutynin and N-desethyloxybutynin demonstrated biphasic elimination with plasma concentrations beginning to decrease 24 hours after dosing. Elimination was more rapid between 24 and 48 hours after dosing, during which time plasma concentrations of oxybutynin and N-desethyloxybutynin declined by about one-half. This rapid elimination phase was followed by a more prolonged terminal elimination phase. The apparent elimination half-lives including the terminal elimination phase were 64 hours and 82 hours for oxybutynin and DEO, respectively. Excretion Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin. Person-to-Person Transference The potential for dermal transfer of oxybutynin from a treated person to an untreated person was evaluated in a single-dose study where subjects dosed with GELNIQUE engaged in vigorous contact with an untreated partner for 15 minutes, either with (N = 14 couples) or without (N = 12 couples) clothing covering the application area. The untreated partners not protected by clothing demonstrated detectable plasma concentrations of oxybutynin (mean C max = 0.94 ng/mL). Two of the 14 untreated subjects participating in the clothing-to-skin contact regimen had measurable oxybutynin plasma concentrations (C max ≤ 0.1 ng/mL) during the 48 hours following contact with treated subjects; oxybutynin was not detectable with the remaining 12 untreated subjects. Use of Sunscreen The effect of sunscreen on the absorption of oxybutynin when applied 30 minutes before or 30 minutes after GELNIQUE application was evaluated in a single-dose randomized crossover study (N = 16). Concomitant application of sunscreen, either before or after GELNIQUE application, had no effect on the systemic exposure of oxybutynin. Showering The effect of showering on the absorption of oxybutynin was evaluated in a randomized, steady-state crossover study under conditions of no shower, or showering 1, 2 or 6 hours after GELNIQUE application (N = 20). The results of the study indicate that showering after one hour does not affect the overall systemic exposure to oxybutynin. Race The effect of race on the pharmacokinetics of GELNIQUE has not been studied. Specific Populations: Geriatric: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on geriatric status in patients following administration of GELNIQUE [see Use in Specific Populations (8.5) ]. Pediatric: The pharmacokinetics of oxybutynin and N-desethyloxybutynin have not been evaluated in individuals younger than 18 years of age [see Use in Specific Populations (8.4) ] . Gender: Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on gender in healthy volunteers following administration of GELNIQUE.

20190301

9

3 DOSAGE FORMS AND STRENGTHS Gel: 10% Gel: 10% ( 3 )

GELNIQUE oxybutynin chloride OXYBUTYNIN CHLORIDE OXYBUTYNIN ALCOHOL GLYCERIN HYDROXYPROPYL CELLULOSE (1600000 WAMW) SODIUM HYDROXIDE WATER GELNIQUE oxybutynin chloride OXYBUTYNIN CHLORIDE OXYBUTYNIN ALCOHOL GLYCERIN HYDROXYPROPYL CELLULOSE (1600000 WAMW) SODIUM HYDROXIDE WATER

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility A 24-month study in rats at dosages of oxybutynin chloride of 20, 80 and 160 mg/kg showed no evidence of carcinogenicity. These doses are approximately 6, 25 and 50 times the maximum exposure in humans taking an oral dose, based on body surface area. Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae, and Salmonella typhimurium test systems. Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no definite evidence of impaired fertility.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility A 24-month study in rats at dosages of oxybutynin chloride of 20, 80 and 160 mg/kg showed no evidence of carcinogenicity. These doses are approximately 6, 25 and 50 times the maximum exposure in humans taking an oral dose, based on body surface area. Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae, and Salmonella typhimurium test systems. Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no definite evidence of impaired fertility.

NDA022204

GELNIQUE

oxybutynin chloride

0023-5861

HUMAN PRESCRIPTION DRUG

TRANSDERMAL

PRINCIPAL DISPLAY PANEL Gelnique ® (oxybutynin chloride) Gel, 10% Carton 1 Pump NDC 0023-5812-30 PRINCIPAL DISPLAY PANEL Gelnique® (oxybutynin chloride) Gel, 10% Carton 1 Pump NDC 0023-5812-30

17 PATIENT COUNSELING INFORMATION See FDA-approved Patient Labeling (Patient Information) Instructions for Use GELNIQUE is for topical application only and should not be ingested. GELNIQUE should not be applied to recently shaved skin surfaces. Patients should wash hands immediately after product application. Application sites should not be subject to showering or water immersion for 1 hour after product application. Application sites should be covered with clothing if close skin-to-skin contact at the application site is anticipated. Alcohol based gels are flammable. Avoid open fire or smoking until the gel has dried. Important Anticholinergic Adverse Reactions Patients should be informed that anticholinergic (antimuscarinic) agents, such as GELNIQUE, may produce clinically significant adverse reactions related to anticholinergic pharmacological activity including: Urinary retention and constipation. Heat prostration (due to decreased sweating) when anticholinergics such as GELNIQUE are used in a hot environment. Dizziness or blurred vision. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until GELNIQUE’s effects have been determined. Drowsiness that may be worsened by alcohol. Distributed By: Allergan USA, Inc. Madison, NJ 07940 © 2019 Allergan. All rights reserved. Gelnique ® is a registered trademark of Allergan Sales, LLC. v1.1USPI5812

14 CLINICAL STUDIES The efficacy and safety of GELNIQUE were evaluated in a single randomized, double-blind, placebo-controlled, parallel group 12-week study for the treatment of overactive bladder with symptoms of urge incontinence, urgency and frequency. Key entry criteria included adults with symptomatic overactive bladder with an average of ≥ 4 incontinence episodes in a 3-day period and at least 8 micturitions per day. Patients were randomized to daily applications of GELNIQUE 1 gram or matching placebo gel. A total of 389 patients received GELNIQUE and 400 patients received placebo gel. The majority of patients were Caucasian (86.3%) and female (89.2%), with a mean age of 59.4 years (range: 18 to 88 years). The average duration of urinary incontinence was approximately 8.5 years and approximately 75% of patients had no prior pharmacological treatment for urinary incontinence. Patients treated with GELNIQUE experienced a statistically significant decrease in the number of urinary incontinence episodes per day from baseline to endpoint compared with placebo (p < 0.0001) as well as a decrease in the average daily urinary frequency (p = 0.0017) and an increase in the average urine volume per void (p = 0.0018). Mean and median change from baseline in daily incontinence episodes (primary endpoint), urinary frequency, and urinary void volume (secondary endpoints) between placebo and GELNIQUE are summarized in Table 3. Table 3: Mean and median change from baseline for incontinence episodes, urinary frequency, and urinary void volume at Week 12 (LOCF*). Parameter GELNIQUE 1 gram (N = 389) Placebo (N = 400) Mean (SD) Median Mean (SD) Median Daily Incontinence Episodes Baseline 5.4 (3.26) 4.7 5.4 (3.28) 4.7 Change from baseline -3.0 (2.73) -2.7 -2.5 (3.06) -2.0 Mean difference [GELNIQUE – placebo] (95% CI) -0.5 (-0.14, -0.87) P-value vs. placebo < 0.0001 Daily Urinary Frequency Baseline 12.4 (3.34) 11.7 12.2 (3.32) 11.3 Change from baseline -2.7 (3.21) -2.7 -2.0 (2.82) -1.7 P-value vs. placebo 0.0017 Urinary Void Volume (mL) Baseline 163.4 (65.85) 160.1 167.9 (68.40) 160.6 Change from Baseline 21.0 (65.33) 11.5 3.8 (53.79) 0.0 P-value vs. placebo 0.0018 *Last-Observation-Carried-Forward statistical imputation for missing data

8.5 Geriatric Use Of the 496 patients exposed to GELNIQUE in the randomized, double-blind, placebo-controlled 12-week study and the 14-week safety extension study, 188 patients (38%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ] .

8.4 Pediatric Use The safety and effectiveness of GELNIQUE 10% have not been established in pediatric patients.

8.1 Pregnancy Risk Summary There are no studies with topical or oral oxybutynin use in pregnant women to inform any drug-associated risks of adverse development outcomes. No adverse developmental outcomes were observed in animal reproduction studies when oxybutynin chloride was administered to pregnant rats and rabbits during organogenesis at approximately 50 and 1 times, respectively, the maximum human dose based on body surface area ( see Data ). In the general U.S. population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20% respectively. Data A n i m al Da t a Subcutaneous administration of oxybutynin chloride to rats at doses up to 25 mg/kg (approximately 50 times the human exposure based on body surface area) and to rabbits at doses up to 0.4 mg/kg (approximately 1 times the human exposure based on body surface area) throughout the period of organogenesis revealed no evidence of harm to the fetus.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no studies with topical or oral oxybutynin use in pregnant women to inform any drug-associated risks of adverse development outcomes. No adverse developmental outcomes were observed in animal reproduction studies when oxybutynin chloride was administered to pregnant rats and rabbits during organogenesis at approximately 50 and 1 times, respectively, the maximum human dose based on body surface area ( see Data ). In the general U.S. population, the estimated background risk of major birth defects and miscarriages in clinically recognized pregnancies is 2-4% and 15-20% respectively. Data A n i m al Da t a Subcutaneous administration of oxybutynin chloride to rats at doses up to 25 mg/kg (approximately 50 times the human exposure based on body surface area) and to rabbits at doses up to 0.4 mg/kg (approximately 1 times the human exposure based on body surface area) throughout the period of organogenesis revealed no evidence of harm to the fetus. 8.2 Lactation Risk Summary There is no information on the presence of oxybutynin or its metabolites in human milk, its effects on milk production or on the breast fed child. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GELNIQUE and any potential adverse effects on the breastfed child from GELNIQUE or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of GELNIQUE 10% have not been established in pediatric patients. 8.5 Geriatric Use Of the 496 patients exposed to GELNIQUE in the randomized, double-blind, placebo-controlled 12-week study and the 14-week safety extension study, 188 patients (38%) were 65 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3) ] .

16 HOW SUPPLIED/STORAGE AND HANDLING Metered-Dose Pump: Metered-dose pump dispenser capable of delivering 30 metered 1 gram doses. Carton of 1 metered-dose Pump (NDC 0023-5812-30) Unit Dose : Heat-sealed sachet containing 1 gram (1.14 mL) of GELNIQUE gel for topical use. Carton of 30 Sachets (NDC 0023-5861-11) Storage Store at 20-25°C (68-77°F). [See USP controlled room temperature.] Protect from moisture and humidity. Apply immediately after the sachets are opened and contents expelled or dose delivered from dispenser. Discard used sachets and empty dispensers in household trash in a manner that prevents accidental application or ingestion by children, pets, or others. Keep out of reach of children.