Oxybutynin chloride

6 ADVERSE REACTIONS The most common (incidence ≥5%) adverse reactions were dry mouth, constipation, diarrhea, headache, somnolence, and dizziness. ( Error! Hyperlink reference not valid. ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or www.accordhealthcare.us 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, the 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 clinical practice. The safety and efficacy of oxybutynin chloride extended-release tablets (5 to 30 mg/day) was evaluated in 774 adult subjects who participated in five double-blind, controlled clinical trials. In four of the five studies, oxybutynin IR (5 to 20 mg/day in 199 subjects) was an active comparator. Adverse reactions reported by ≥ 1% of subjects are shown in Table 1. Table 1: Adverse Drug Reactions Reported by ≥ 1% of Oxybutynin Chloride Extended-Release Tablets-treated Adult Subjects in Five Double-blind, Controlled Clinical Trials of Oxybutynin Chloride Extended-Release Tablets System/Organ Class Preferred Term Oxybutynin ER 5 to 30 mg/day n = 774 % Oxybutynin IR IR = immediate release 5 to 20 mg/day n = 199 % Psychiatric Disorders Insomnia 3.0 5.5 Nervous System Disorders Headache 7.5 8.0 Somnolence 5.6 14.1 Dizziness 5.0 16.6 Dysgeusia 1.6 1.5 Eye Disorders Vision blurred 4.3 9.6 Dry eye 3.1 2.5 Respiratory, Thoracic and Mediastinal Disorders Cough 1.9 3.0 Oropharyngeal pain 1.9 1.5 Dry throat 1.7 2.5 Nasal dryness 1.7 4.5 Gastrointestinal Disorders Dry mouth 34.9 72.4 Constipation 8.7 15.1 Diarrhea 7.9 6.5 Dyspepsia 4.5 6.0 Nausea 4.5 11.6 Abdominal pain 1.6 2.0 Vomiting 1.3 1.5 Flatulence 1.2 2.5 Gastro-esophageal reflux disease 1.0 0.5 Skin and Subcutaneous Tissue Disorders Dry skin 1.8 2.5 Pruritus 1.3 1.5 Renal and Urinary Disorders Dysuria 1.9 2.0 Urinary hesitation 1.9 8.5 Urinary retention 1.2 3.0 General Disorders and Administration Site Conditions Fatigue 2.6 3.0 Investigations Residual urine volume The bundled term residual urine volume consists of the preferred terms residual urine volume and residual urine volume increased. 2.3 3.5 The discontinuation rate due to adverse reactions was 4.4% with oxybutynin ER compared to 0% with oxybutynin IR. The most frequent adverse reaction causing discontinuation of study medication was dry mouth (0.7% ). The following adverse reactions were reported by <1% of oxybutynin chloride extended-release tablets-treated patients and at a higher incidence than placebo in clinical trials: Metabolism and Nutrition Disorders: anorexia, fluid retention; Vascular disorders: hot flush; Respiratory, thoracic and mediastinal disorders: dysphonia; Gastrointestinal Disorders: dysphagia, frequent bowel movements; General disorders and administration site conditions: chest discomfort, thirst. 6.2 Postmarketing Experience The following additional adverse reactions have been reported from worldwide postmarketing experience with oxybutynin chloride extended-release tablets. Because postmarketing 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. Infections and Infestations: Urinary tract infection; Psychiatric Disorders: psychotic disorder, agitation, confusional state, hallucinations, memory impairment, abnormal behavior; Nervous System Disorders: convulsions; Eye Disorders: glaucoma; Respiratory, Thoracic and Mediastinal Disorders: nasal congestion; Cardiac Disorders: arrhythmia, tachycardia, palpitations, QT interval prolongation; Vascular Disorders: flushing, hypertension; Skin and Subcutaneous Tissue Disorders: rash; Renal and Urinary Disorders: impotence; General Disorders and Administration Site Conditions: hypersensitivity reactions, including angioedema with airway obstruction, urticaria, and face edema; anaphylactic reactions requiring hospitalization for emergency treatment; Injury, poisoning and procedural complications: fall. Additional adverse events reported with some other oxybutynin chloride formulations include: cycloplegia, mydriasis, and suppression of lactation.

4 CONTRAINDICATIONS Oxybutynin chloride extended-release tablets are contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma. Oxybutynin chloride extended-release tablets are also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product. There have been reports of hypersensitivity reactions, including anaphylaxis and angiodema. • Urinary retention ( Error! Hyperlink reference not valid. ) • Gastric Retention ( Error! Hyperlink reference not valid. ) • Uncontrolled narrow angle glaucoma ( Error! Hyperlink reference not valid. ) • Known hypersensitivity to oxybutynin chloride extended-release tablets, oxybutynin or any component of oxybutynin chloride extended-release tablets ( Error! Hyperlink reference not valid. )

11 DESCRIPTION Oxybutynin chloride extended-release tablet, USP is an antispasmodic, muscarinic antagonist. Each oxybutynin chloride extended-release tablet, USP contains 5 mg, 10 mg, or 15 mg of oxybutynin chloride USP, formulated as a once-a-day controlled-release tablet for oral administration. Oxybutynin chloride is administered as a racemate of R- and S-enantiomers. Chemically, oxybutynin chloride is d,l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate hydrochloride. The empirical formula of oxybutynin chloride is C 22 H 31 NO 3 •HCl. Its structural formula is: Oxybutynin chloride is a white crystalline solid with a molecular weight of 393.9. It is readily soluble in water and acids, but relatively insoluble in alkalis. Oxybutynin chloride extended-release tablets, USP contains the following inert ingredients: colloidal anhydrous silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer type-c, microcrystalline cellulose, polyethylene glycol, sodium bicarbonate, sodium lauryl sulfate, talc, titanium dioxide, triethyl citrate. Coloring agents are ferric oxide yellow (in all strengths), ferric oxide red (in 5 mg and 10 mg only) and ferric oxide black (in 15 mg only). System Components and Performance Oxybutynin chloride extended-release tablets, USP are formulated to deliver oxybutynin chloride at a controlled rate over approximately 24 hours. The dosage form is comprised of a hydrophilic cellulose polymer matrix tablet surrounded by an enteric coating system. The enteric coat is insoluble in the low pH environment of the stomach. As the tablet passes through the stomach and enters the higher pH environment of the small intestine, the enteric coating dissolves and/or erodes to expose the polymer matrix tablet which swells and releases drug at a controlled rate via diffusion and/or erosion. Oxybutynin chloride extended-release tablets, USP meets USP dissolution test 5. Chemical Structure

2 DOSAGE AND ADMINISTRATION Oxybutynin chloride extended-release tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed. Oxybutynin chloride extended-release tablets may be administered with or without food. Oxybutynin chloride extended-release tablets must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed. Oxybutynin chloride extended-release tablets may be administered with or without food. ( Error! Hyperlink reference not valid. ) • Adults: Start with 5 mg or 10 mg, once daily at approximately the same time every day. Dose should not exceed 30 mg per day. ( 2.1 ) • Pediatric patients (6 years of age or older): Start with 5 mg, once daily at approximately the same time every day. Dose should not exceed 20 mg per day. ( 2.2 ) 2.1 Adults The recommended starting dose of Oxybutynin chloride extended-release tablet is 5 or 10 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 30 mg/day). In general, dosage adjustment may proceed at approximately weekly intervals. 2.2 Pediatric Patients Aged 6 Years of Age and Older The recommended starting dose of oxybutynin chloride extended-release tablet is 5 mg once daily at approximately the same time each day. Dosage may be adjusted in 5-mg increments to achieve a balance of efficacy and tolerability (up to a maximum of 20 mg/day).

1 INDICATIONS AND USAGE Oxybutynin chloride extended-release tablets are muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Oxybutynin chloride extended-release tablets are also indicated for the treatment of pediatric patients aged 6 years and older with symptoms of detrusor overactivity associated with a neurological condition (e.g., spina bifida). • Oxybutynin chloride extended-release tablets are a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. ( Error! Hyperlink reference not valid. ) • Oxybutynin chloride extended-release tablets are also indicated for the treatment of pediatric patients aged 6 years and older with symptoms of detrusor overactivity associated with a neurological condition (e.g., spina bifida). ( Error! Hyperlink reference not valid. )

10 OVERDOSAGE The continuous release of oxybutynin from oxybutynin chloride extended-release tablets should be considered in the treatment of overdosage. Patients should be monitored for at least 24 hours. Treatment should be symptomatic and supportive. A cathartic may be administered. Overdosage with oxybutynin chloride has been associated with anticholinergic effects including central nervous system excitation, flushing, fever, dehydration, cardiac arrhythmia, vomiting, and urinary retention. Ingestion of 100 mg oxybutynin chloride in association with alcohol has been reported in a 13-year-old boy who experienced memory loss, and 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 fully recovered with symptomatic treatment.

7 DRUG INTERACTIONS The concomitant use of oxybutynin with other anticholinergic drugs or with other agents which produce dry mouth, constipation, somnolence (drowsiness), and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. This may be of concern for drugs with a narrow therapeutic index. Anticholinergic agents may also antagonize the effects of prokinetic agents, such as metoclopramide. Mean oxybutynin chloride plasma concentrations were approximately 2 fold higher when oxybutynin chloride extended-release tablet was administered with ketoconazole, a potent CYP3A4 inhibitor. Other inhibitors of the cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin), may alter oxybutynin mean pharmacokinetic parameters (i.e., C max and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered. • Co-administration with other anticholinergic drugs may increase the frequency and/or severity of anticholinergic-like effects. ( Error! Hyperlink reference not valid. ) • Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic exposure of oxybutynin. ( Error! Hyperlink reference not valid. )

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Oxybutynin relaxes bladder smooth muscle. Oxybutynin chloride exerts a direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects). Antimuscarinic activity resides predominantly in the R-isomer. A metabolite, desethyloxybutynin, has pharmacological activity similar to that of oxybutynin in in vitro studies. 12.2 Pharmacodynamics In patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that oxybutynin increases bladder (vesical) capacity, diminishes the frequency of uninhibited contractions of the detrusor muscle, and delays the initial desire to void. 12.3 Pharmacokinetics Absorption Following the first dose of oxybutynin chloride extended-release tablets oxybutynin plasma concentrations rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours, minimizing fluctuations between peak and trough concentrations associated with oxybutynin. The relative bioavailabilities of R- and S-oxybutynin from oxybutynin chloride extended-release tablets are 156% and 187%, respectively, compared with oxybutynin. The mean pharmacokinetic parameters for R- and S-oxybutynin are summarized in Table 2. The plasma concentration-time profiles for R- and S-oxybutynin are similar in shape; Figure 1 shows the profile for R-oxybutynin. Table 2: Mean (SD) R- and S-Oxybutynin Pharmacokinetic Parameters Following a Single Dose of Oxybutynin Chloride Extended-Release Tablets 10 mg (n=43) Parameters (units) R-Oxybutynin S-Oxybutynin C max (ng/mL) 1.0 (0.6) 1.8 (1.0) T max (h) 12.7 (5.4) 11.8 (5.3) t 1/2 (h) 13.2 (6.2) 12.4 (6.1) AUC (0–48) (ng∙h/mL) 18.4 (10.3) 34.2 (16.9) AUC inf (ng∙h/mL) 21.3 (12.2) 39.5 (21.2) Figure 1: Mean R-oxybutynin plasma concentrations following a single dose of oxybutynin chloride extended-release tablets 10 mg and oxybutynin 5 mg administered every 8 hours (n=23 for each treatment). Steady state oxybutynin plasma concentrations are achieved by Day 3 of repeated oxybutynin chloride extended-release tablets dosing, with no observed drug accumulation or change in oxybutynin and desethyloxybutynin pharmacokinetic parameters. Oxybutynin chloride extended-release tablets steady state pharmacokinetics were studied in 19 children aged 5 to 15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The children were on oxybutynin chloride extended-release tablets total daily dose ranging from 5 to 20 mg (0.10 to 0.77 mg/kg). Sparse sampling technique was used to obtain serum samples. When all available data are normalized to an equivalent of 5 mg per day of oxybutynin chloride extended-release tablets, the mean pharmacokinetic parameters derived for R- and S-oxybutynin and R- and S-desethyloxybutynin are summarized in Table 3. The plasma-time concentration profiles for R- and S-oxybutynin are similar in shape; Figure 2 shows the profile for R-oxybutynin when all available data are normalized to an equivalent of 5 mg per day. Table 3: Mean ± SD R- and S-Oxybutynin and R- and S-Desethyloxybutynin Pharmacokinetic Parameters in Children Aged 5 to 15 Following Administration of 5 to 20 mg Oxybutynin Chloride Extended-Release Tablets Once Daily (n=19), All Available Data Normalized to an Equivalent of Oxybutynin Chloride Extended-Release Tablets 5 mg Once Daily R-Oxybutynin S-Oxybutynin R- Desethyloxybutynin S- Desethyloxybutynin C max (ng/mL) 0.7 ± 0.4 1.3 ± 0.8 7.8 ± 3.7 4.2 ± 2.3 T max (h) 5.0 5.0 5.0 5.0 AUC (ng∙h/mL) 12.8 ± 7.0 23.7 ± 14.4 125.1 ± 66.7 73.6 ± 47.7 Figure 2: Mean steady state (± SD) R-oxybutynin plasma concentrations following administration of 5 to 20 mg oxybutynin chloride extended-release tablets once daily in children aged 5 to 15. Plot represents all available data normalized to an equivalent of oxybutynin chloride extended-release tablets 5 mg once daily. Food Effects The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions. Figure 1 Figure 2 Distribution Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution is 193 L after intravenous administration of 5 mg oxybutynin chloride. Both enantiomers of oxybutynin are highly bound (>99%) to plasma proteins. Both enantiomers of N-desethyloxybutynin are also highly bound (>97%) to plasma proteins. The major binding protein is alpha-1 acid glycoprotein. Metabolism Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall. Its metabolic products include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and desethyloxybutynin, which is pharmacologically active. Following oxybutynin chloride extended-release tablets administration, plasma concentrations of R- and S-desethyloxybutynin are 73% and 92%, respectively, of concentrations observed with oxybutynin. Excretion Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite desethyloxybutynin. Dose Proportionality Pharmacokinetic parameters of oxybutynin and desethyloxybutynin (C max and AUC) following administration of 5 to 20 mg of oxybutynin chloride extended-release tablets are dose proportional. Use in Specific Populations Pediatric The pharmacokinetics of oxybutynin chloride extended-release tablets were evaluated in 19 children aged 5 to 15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The pharmacokinetics of oxybutynin chloride extended-release tablets in these pediatric patients were consistent with those reported for adults (see Tables 2 and 3 , and Figures 1 and 2 above). Gender There are no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following administration of oxybutynin chloride extended-release tablets. Race Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on race in healthy volunteers following administration of oxybutynin chloride extended-release tablets.

12.1 Mechanism of Action Oxybutynin relaxes bladder smooth muscle. Oxybutynin chloride exerts a direct antispasmodic effect on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth muscle. No blocking effects occur at skeletal neuromuscular junctions or autonomic ganglia (antinicotinic effects). Antimuscarinic activity resides predominantly in the R-isomer. A metabolite, desethyloxybutynin, has pharmacological activity similar to that of oxybutynin in in vitro studies.

12.2 Pharmacodynamics In patients with conditions characterized by involuntary bladder contractions, cystometric studies have demonstrated that oxybutynin increases bladder (vesical) capacity, diminishes the frequency of uninhibited contractions of the detrusor muscle, and delays the initial desire to void.

12.3 Pharmacokinetics Absorption Following the first dose of oxybutynin chloride extended-release tablets oxybutynin plasma concentrations rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours, minimizing fluctuations between peak and trough concentrations associated with oxybutynin. The relative bioavailabilities of R- and S-oxybutynin from oxybutynin chloride extended-release tablets are 156% and 187%, respectively, compared with oxybutynin. The mean pharmacokinetic parameters for R- and S-oxybutynin are summarized in Table 2. The plasma concentration-time profiles for R- and S-oxybutynin are similar in shape; Figure 1 shows the profile for R-oxybutynin. Table 2: Mean (SD) R- and S-Oxybutynin Pharmacokinetic Parameters Following a Single Dose of Oxybutynin Chloride Extended-Release Tablets 10 mg (n=43) Parameters (units) R-Oxybutynin S-Oxybutynin C max (ng/mL) 1.0 (0.6) 1.8 (1.0) T max (h) 12.7 (5.4) 11.8 (5.3) t 1/2 (h) 13.2 (6.2) 12.4 (6.1) AUC (0–48) (ng∙h/mL) 18.4 (10.3) 34.2 (16.9) AUC inf (ng∙h/mL) 21.3 (12.2) 39.5 (21.2) Figure 1: Mean R-oxybutynin plasma concentrations following a single dose of oxybutynin chloride extended-release tablets 10 mg and oxybutynin 5 mg administered every 8 hours (n=23 for each treatment). Steady state oxybutynin plasma concentrations are achieved by Day 3 of repeated oxybutynin chloride extended-release tablets dosing, with no observed drug accumulation or change in oxybutynin and desethyloxybutynin pharmacokinetic parameters. Oxybutynin chloride extended-release tablets steady state pharmacokinetics were studied in 19 children aged 5 to 15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The children were on oxybutynin chloride extended-release tablets total daily dose ranging from 5 to 20 mg (0.10 to 0.77 mg/kg). Sparse sampling technique was used to obtain serum samples. When all available data are normalized to an equivalent of 5 mg per day of oxybutynin chloride extended-release tablets, the mean pharmacokinetic parameters derived for R- and S-oxybutynin and R- and S-desethyloxybutynin are summarized in Table 3. The plasma-time concentration profiles for R- and S-oxybutynin are similar in shape; Figure 2 shows the profile for R-oxybutynin when all available data are normalized to an equivalent of 5 mg per day. Table 3: Mean ± SD R- and S-Oxybutynin and R- and S-Desethyloxybutynin Pharmacokinetic Parameters in Children Aged 5 to 15 Following Administration of 5 to 20 mg Oxybutynin Chloride Extended-Release Tablets Once Daily (n=19), All Available Data Normalized to an Equivalent of Oxybutynin Chloride Extended-Release Tablets 5 mg Once Daily R-Oxybutynin S-Oxybutynin R- Desethyloxybutynin S- Desethyloxybutynin C max (ng/mL) 0.7 ± 0.4 1.3 ± 0.8 7.8 ± 3.7 4.2 ± 2.3 T max (h) 5.0 5.0 5.0 5.0 AUC (ng∙h/mL) 12.8 ± 7.0 23.7 ± 14.4 125.1 ± 66.7 73.6 ± 47.7 Figure 2: Mean steady state (± SD) R-oxybutynin plasma concentrations following administration of 5 to 20 mg oxybutynin chloride extended-release tablets once daily in children aged 5 to 15. Plot represents all available data normalized to an equivalent of oxybutynin chloride extended-release tablets 5 mg once daily. Food Effects The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions. Figure 1 Figure 2 Distribution Oxybutynin is widely distributed in body tissues following systemic absorption. The volume of distribution is 193 L after intravenous administration of 5 mg oxybutynin chloride. Both enantiomers of oxybutynin are highly bound (>99%) to plasma proteins. Both enantiomers of N-desethyloxybutynin are also highly bound (>97%) to plasma proteins. The major binding protein is alpha-1 acid glycoprotein. Metabolism Oxybutynin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall. Its metabolic products include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and desethyloxybutynin, which is pharmacologically active. Following oxybutynin chloride extended-release tablets administration, plasma concentrations of R- and S-desethyloxybutynin are 73% and 92%, respectively, of concentrations observed with oxybutynin. Excretion Oxybutynin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite desethyloxybutynin. Dose Proportionality Pharmacokinetic parameters of oxybutynin and desethyloxybutynin (C max and AUC) following administration of 5 to 20 mg of oxybutynin chloride extended-release tablets are dose proportional. Use in Specific Populations Pediatric The pharmacokinetics of oxybutynin chloride extended-release tablets were evaluated in 19 children aged 5 to 15 years with detrusor overactivity associated with a neurological condition (e.g., spina bifida). The pharmacokinetics of oxybutynin chloride extended-release tablets in these pediatric patients were consistent with those reported for adults (see Tables 2 and 3 , and Figures 1 and 2 above). Gender There are no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following administration of oxybutynin chloride extended-release tablets. Race Available data suggest that there are no significant differences in the pharmacokinetics of oxybutynin based on race in healthy volunteers following administration of oxybutynin chloride extended-release tablets.

20220601

1

3 DOSAGE FORMS AND STRENGTHS Oxybutynin chloride extended-release tablets, USP are available as 5, 10 and 15 mg tablets for oral use: 5 mg: Pale yellow colored, round shaped, biconvex coated tablets imprinted with "EM1" on one side and plain on other side. 10 mg: Pink colored, round shaped, biconvex coated tablets imprinted with "EM2" on one side and plain on other side. 15 mg: Grey colored, round shaped, biconvex coated tablets imprinted with "EM3" on one side and plain on other side. Extended release tablets 5 mg, 10 mg and 15 mg ( Error! Hyperlink reference not valid. )

oxybutynin chloride oxybutynin chloride POLYETHYLENE GLYCOL 400 SODIUM BICARBONATE SODIUM LAURYL SULFATE TALC TITANIUM DIOXIDE TRIETHYL CITRATE FERRIC OXIDE YELLOW FERRIC OXIDE RED SILICON DIOXIDE HYPROMELLOSE 2208 (100000 MPA.S) HYPROMELLOSE 2910 (6 MPA.S) LACTOSE MONOHYDRATE MAGNESIUM STEARATE METHACRYLIC ACID AND ETHYL ACRYLATE COPOLYMER MICROCRYSTALLINE CELLULOSE OXYBUTYNIN CHLORIDE OXYBUTYNIN EM2

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/day showed no evidence of carcinogenicity. These doses are approximately 6, 25, and 50 times the maximum human exposure, based on a human equivalent dose taking into account normalization of 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 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/day showed no evidence of carcinogenicity. These doses are approximately 6, 25, and 50 times the maximum human exposure, based on a human equivalent dose taking into account normalization of 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 evidence of impaired fertility.

ANDA207138

Oxybutynin chloride

oxybutynin chloride

71205-667

HUMAN PRESCRIPTION DRUG

ORAL

Oxybutynin chloride extended-release tablets 71205-667-30

For more information, go to www.accordhealthcare.us or call Accord Healthcare Inc. at 1-866-941-7875. Manufactured For: Accord Healthcare, Inc., 1009 Slater Road, Suite 210-B, Durham, NC 27703, USA. Manufactured By: Intas Pharmaceuticals Limited, Plot No. : 457, 458, Village – Matoda, Bavla Road, Ta.- Sanand, Dist.- Ahmedabad – 382 210, INDIA. Repackaged By: Proficient Rx LP Thousand Oaks, CA 91320 10 1091 1 697321 Issued May 2019

17 PATIENT COUNSELING INFORMATION • Patients should be informed that oxybutynin may produce angioedema that could result in life threatening airway obstruction. Patients should be advised to promptly discontinue oxybutynin therapy and seek immediate medical attention if they experience swelling of the tongue, edema of the laryngopharynx, or difficulty breathing. • Patients should be informed that anticholinergic (antimuscarinic) agents such as oxybutynin chloride extended-release tablets, may produce clinically significant adverse reactions related to anticholinergic activity such as: • Urinary retention and constipation • Heat prostration due to decreased sweating. Heat prostration can occur when anticholinergic medicines are administered in the presence of high environmental temperature. • Patients should be informed that anticholinergic medicines such as oxybutynin chloride extended-release tablets may produce drowsiness (somnolence), dizziness or blurred vision. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until oxybutynin chloride extended-release tablets effects have been determined. • Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as oxybutynin chloride extended-release tablets. • Patients should be informed that oxybutynin chloride extended-release tablets should be swallowed whole with the aid of liquids. Patients should not chew, divide, or crush tablets. • Oxybutynin chloride extended-release tablets should be taken at approximately the same time each day.

14 CLINICAL STUDIES Oxybutynin chloride extended-release tablets were evaluated for the treatment of patients with overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in three controlled efficacy studies. The majority of patients were Caucasian (89.0%) and female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge) as evidenced by ≥ 6 urge incontinence episodes per week and ≥ 10 micturitions per day. Study 1 was a fixed-dose escalation design, whereas the other two studies used a dose-adjustment design in which each patient's final dose was adjusted to a balance between improvement of incontinence symptoms and tolerability of side effects. All three studies included patients known to be responsive to oxybutynin or other anticholinergic medications, and these patients were maintained on a final dose for up to 2 weeks. The efficacy results for the three controlled trials are presented in the following tables and figures. Number of Urge Urinary Incontinence Episodes Per Week Study 1 n Oxybutynin ER n Placebo Mean Baseline 34 15.9 16 20.9 Mean (SD) Change from Baseline + 34 -15.8 (8.9) 16 -7.6 (8.6) 95% Confidence Interval for Difference (-13.6, -2.8) * (Oxybutynin ER- Placebo) * The difference between Oxybutynin ER and placebo was statistically significant. + Covariate adjusted mean with missing observations set to baseline values Study 2 n Oxybutynin ER n oxybutynin Mean Baseline 53 27.6 52 23.0 Mean (SD) Change from Baseline + 53 -17.6 (11.9) 52 -19.4 (11.9) 95% Confidence Interval for Difference (-2.8, 6.5) (Oxybutynin ER - oxybutynin) + Covariate adjusted mean with missing observations set to baseline values Study 3 n Oxybutynin ER n oxybutynin Mean Baseline 111 18.9 115 19.5 Mean (SD) Change from Baseline + 111 -14.5 (8.7) 115 -13.8 (8.6) 95% Confidence Interval for Difference (-3.0, 1.6) ** (Oxybutynin ER - oxybutynin) + Covariate adjusted mean with missing observations set to baseline values> ** The difference between Oxybutynin ER and oxybutynin fulfilled the criteria for comparable efficacy. Figure 3 Figure 4 Figure 5

8.5 Geriatric Use The rate and severity of anticholinergic effects reported by patients less than 65 years old and those 65 years and older were similar. The pharmacokinetics of oxybutynin chloride extended-release tablets were similar in all patients studied (up to 78 years of age).

8.3 Nursing Mothers It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when oxybutynin chloride extended-release tablets are administered to a nursing woman.

8.4 Pediatric Use The safety and efficacy of oxybutynin chloride extended-release tablets were studied in 60 children in a 24-week, open-label, non-randomized trial. Patients were aged 6 to 15 years, all had symptoms of detrusor overactivity in association with a neurological condition (e.g., spina bifida), all used clean intermittent catheterization, and all were current users of oxybutynin chloride. Study results demonstrated that administration of oxybutynin chloride extended-release tablets 5 to 20 mg/day was associated with an increase from baseline in mean urine volume per catheterization from 108 mL to 136 mL, an increase from baseline in mean urine volume after morning awakening from 148 mL to 189 mL, and an increase from baseline in the mean percentage of catheterizations without a leaking episode from 34% to 51%. Urodynamic results were consistent with clinical results. Administration of oxybutynin chloride extended-release tablets resulted in an increase from baseline in mean maximum cystometric capacity from 185 mL to 254 mL, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 44 cm H 2 O to 33 cm H 2 O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H 2 O) from 60% to 28%. The pharmacokinetics of oxybutynin chloride extended-release tablets in these patients were consistent with those reported for adults [see Error! Hyperlink reference not valid. ] . Oxybutynin chloride extended-release tablets are not recommended in pediatric patients who cannot swallow the tablet whole without chewing, dividing, or crushing, or in children under the age of 6.

8.1 Pregnancy Pregnancy Category B. There are no adequate and well-controlled studies using oxybutynin chloride extended-release tablets in pregnant women. Oxybutynin chloride extended-release tablets should be used during pregnancy only if the potential benefit to the patient outweighs the risk to the patient and fetus. Women who become pregnant during oxybutynin chloride extended-release tablets treatment are encouraged to contact their physician. Risk Summary Based on animal data, oxybutynin is predicted to have a low probability of increasing the risk of adverse developmental effects above background risk. Animal Data Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility or harm to the animal fetus.

8 USE IN SPECIFIC POPULATIONS • Pediatric Use: Oxybutynin chloride extended-release tablets are not recommended in pediatric patients who cannot swallow the tablet whole without chewing, dividing or crushing, or in children under the age of 6 years. ( Error! Hyperlink reference not valid. ) • Renal or Hepatic Impairment: There have been no studies conducted in patients with renal or hepatic impairment. ( 8.6 , 8.7 ) 8.1 Pregnancy Pregnancy Category B. There are no adequate and well-controlled studies using oxybutynin chloride extended-release tablets in pregnant women. Oxybutynin chloride extended-release tablets should be used during pregnancy only if the potential benefit to the patient outweighs the risk to the patient and fetus. Women who become pregnant during oxybutynin chloride extended-release tablets treatment are encouraged to contact their physician. Risk Summary Based on animal data, oxybutynin is predicted to have a low probability of increasing the risk of adverse developmental effects above background risk. Animal Data Reproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility or harm to the animal fetus. 8.3 Nursing Mothers It is not known whether oxybutynin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when oxybutynin chloride extended-release tablets are administered to a nursing woman. 8.4 Pediatric Use The safety and efficacy of oxybutynin chloride extended-release tablets were studied in 60 children in a 24-week, open-label, non-randomized trial. Patients were aged 6 to 15 years, all had symptoms of detrusor overactivity in association with a neurological condition (e.g., spina bifida), all used clean intermittent catheterization, and all were current users of oxybutynin chloride. Study results demonstrated that administration of oxybutynin chloride extended-release tablets 5 to 20 mg/day was associated with an increase from baseline in mean urine volume per catheterization from 108 mL to 136 mL, an increase from baseline in mean urine volume after morning awakening from 148 mL to 189 mL, and an increase from baseline in the mean percentage of catheterizations without a leaking episode from 34% to 51%. Urodynamic results were consistent with clinical results. Administration of oxybutynin chloride extended-release tablets resulted in an increase from baseline in mean maximum cystometric capacity from 185 mL to 254 mL, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 44 cm H 2 O to 33 cm H 2 O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H 2 O) from 60% to 28%. The pharmacokinetics of oxybutynin chloride extended-release tablets in these patients were consistent with those reported for adults [see Error! Hyperlink reference not valid. ] . Oxybutynin chloride extended-release tablets are not recommended in pediatric patients who cannot swallow the tablet whole without chewing, dividing, or crushing, or in children under the age of 6. 8.5 Geriatric Use The rate and severity of anticholinergic effects reported by patients less than 65 years old and those 65 years and older were similar. The pharmacokinetics of oxybutynin chloride extended-release tablets were similar in all patients studied (up to 78 years of age). 8.6 Renal Impairment There were no studies conducted with oxybutynin chloride extended-release tablets in patients with renal impairment. 8.7 Hepatic Impairment There were no studies conducted with oxybutynin chloride extended-release tablets in patients with hepatic impairment.

16 HOW SUPPLIED/STORAGE AND HANDLING Oxybutynin chloride extended-release tablets, USP are available in 10 mg (pink) and are imprinted on one side with "EM2" with black ink. Oxybutynin chloride extended-release tablets, USP are supplied in bottles of 30, 60, and 90 tablets. 10 mg 30 count bottle 60 count bottle 90 count bottle NDC 71205-667-30 NDC 71205-667-60 NDC 71205-667-90 Storage Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and humidity. Keep out of reach of children.

Storage Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and humidity. Keep out of reach of children.