24 HR oxybutynin chloride 15 MG Extended Release Oral Tablet

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. )

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).

WARNINGS AND PRECAUTIONS • Angioedema: Angioedema has been reported with oxybutynin. If symptoms of angioedema occur, discontinue oxybutynin chloride extended-release tablets immediately and initiate appropriate therapy. ( 5.1 ) • Central Nervous System (CNS) effects: CNS effects have been reported with oxybutynin. If patient experiences anticholinergic CNS effects, consider dose adjustment or discontinuation of oxybutynin chloride extended-release tablets. ( 5.2 ) • Use with caution due to aggravation of symptoms: • Pre-existing dementia in patients treated with cholinesterase inhibitors ( 5.2 ), • Parkinson’s disease ( 5.2 ), • Myasthenia gravis ( 5.3 ), and • Decreased gastrointestinal motility in patients with autonomic neuropathy. ( 5.4 ). • Urinary Retention: Use with caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention ( 5.5 ) • Gastrointestinal Adverse Reactions: Use with caution in patients with gastrointestinal obstructive disorders or decreased intestinal motility due to risk of gastric retention. Use with caution in patients with gastroesophageal reflux or in patients concurrently taking drugs that can exacerbate esophagitis. ( 5.6 ) 5.1 Angioedema Angioedema of the face, lips, tongue and/or larynx has been reported with oxybutynin. In some cases, angioedema occurred after the first dose. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, oxybutynin should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided. 5.2 Central Nervous System Effects Oxybutynin is associated with anticholinergic central nervous system (CNS) effects [see Error! Hyperlink reference not valid. ] . A variety of CNS anticholinergic effects have been reported, including hallucinations, agitation, confusion and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly in the first few months after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how oxybutynin chloride extended-release tablet affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Oxybutynin chloride extended-release tablets should be used with caution in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms. Oxybutynin chloride extended-release tablets should be used with caution in patients with Parkinson’s disease due to the risk of aggravation of symptoms. 5.3 Worsening of Symptoms of Myasthenia Gravis Oxybutynin chloride extended-release tablets should be used with caution in patients with myasthenia gravis due to the risk of aggravation of symptoms. 5.4 Worsening of Symptoms of Decreased Gastrointestinal Motility in Patients with Autonomic Neuropathy Oxybutynin chloride extended-release tablets should be used with caution in patients with autonomic neuropathy due to the risk of aggravation of symptoms of decreased gastrointestinal motility. 5.5 Urinary Retention Oxybutynin chloride extended-release tablets should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see Error! Hyperlink reference not valid. ] . 5.6 Gastrointestinal Adverse Reactions Oxybutynin chloride extended-release tablets should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [see Error! Hyperlink reference not valid. ] . Oxybutynin chloride extended-release tablets, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis and intestinal atony. Oxybutynin chloride extended-release tablets should be used with caution in patients who have gastroesophageal reflux and/or who are concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis. As with any other nondeformable material, caution should be used when administering oxybutynin chloride extended-release tablets to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of other drugs in nondeformable controlled-release formulations.

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. )

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). [Figure 1] 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. [Figure 2] Food Effects The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions. 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.