tic 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 coadministered.

receiving oxybutynin chloride 5 to 20 mg/day were the expected side effects of anticholinergic agents. the incidence of dry mouth was dose-related. in addition, the following adverse events were reported by 1 to < 5% of patients using oxybutynin chloride (5 to 20 mg/day) in all studies. infections and infestations: nasopharyngitis, upper respiratory tract infection, bronchitis, cystitis, fungal infection; metabolism and nutrition disorders: fluid retention; psychiatric disorders: confusional state; nervous system disorders: dysgeusia, sinus headache; eye disorders: keratoconjunctivitis sicca, eye irritation; cardiac disorders: palpitations, sinus arrhythmia; vascular disorders: flushing; respiratory, thoracic and mediastinal disorders: nasal dryness, cough, pharyngolaryngeal pain, dry throat, sinus congestion, hoarseness, asthma, nasal congestion; gastrointestinal disorders: diarrhea, abdominal pain, loose stools, flatulence, vomiting, abdominal pain upper, dysphagia, aptyalism, eructation, tongue coated; skin and subcutaneous tissue disorders: dry skin, pruritis; musculoskeletal and connective tissue disorders: back pain, arthralgia, pain in extremity, flank pain; renal and urinary disorders: dysuria, pollakiuria; general disorders and administration site conditions: fatigue, edema peripheral, asthenia, pain, thirst, edema; investigations: blood pressure increased, blood glucose increased, blood pressure decreased; injury, poisoning, and procedural complications: fall. postmarketing surveillance because postmarketing adverse events 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. the following additional adverse events have been reported from worldwide postmarketing experience with oxybutynin chloride: psychiatric disorders: psychotic disorder, agitation, hallucination, memory impairment; nervous system disorders: convulsions; eye disorders: cycloplegia, mydriasis, glaucoma; cardiac disorders: tachycardia, qt interval prolongation; chest discomfort ; gastrointestinal disorders: decreased gastrointestinal motility; frequent bowel movements; skin and subcutaneous tissue disorders: rash, decreased sweating; renal and urinary disorders: impotence; reproductive system and breast disorders: suppression of lactation; general disorders and administration site conditions: hypersensitivity reactions, including angioedema with airway obstruction, urticaria, and face edema; rare anaphylactic reactions requiring hospitalization for emergency treatment; metabolism and nutrition disorders : anorexia; respiratory, thoracic and mediastinal disorders : dysphonia. to report suspected adverse reactions, contact strides pharma inc. at 1-877-244-9825 or go to www.strides.com or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

tic 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 coadministered.

eline in the mean percentage of catheterizations without a leaking episode from 43% to 61%. urodynamic results in these patients were consistent with the clinical results. treatment with oxybutynin chloride tablets was associated with an increase from baseline in maximum cystometric capacity from 230 ml to 279 ml, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 36 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 39% to 20%. as there is insufficient clinical data for pediatric populations under age 5, oxybutynin chloride is not recommended for this age group.

, has pharmacological activity similar to that of oxybutynin in in vitro studies. pharmacokinetics absorption following oral administration of oxybutynin chloride, oxybutynin is rapidly absorbed achieving c max within an hour, following which plasma concentration decreases with an effective half-life of approximately 2 to 3 hours. the absolute bioavailability of oxybutynin is reported to be about 6% (range 1.6 to 10.9%) for the tablets. wide interindividual variation in pharmacokinetic parameters is evident following oral administration of oxybutynin. the mean pharmacokinetic parameters for r- and s-oxybutynin are summarized in table 1. the plasma concentration-time profiles for r- and s-oxybutynin are similar in shape; figure 1 shows the profile for r-oxybutynin. parameters (units) r-oxybutynin s-oxybutynin c max (ng/ml) 3.6 (2.2) 7.8 (4.1) t max (h) 0.89 (0.34) 0.65 (0.32) auc t (ng•h/ml) 22.6 (11.3) 35.0 (17.3) auc inf (ng•h/ml) 24.3 (12.3) 37.3 (18.7) figure 1. mean r-oxybutynin plasma concentrations following three doses of oxybutynin chloride 5 mg administered every 8 hours for 1 day in 23 healthy adult volunteers oxybutynin chloride steady-state pharmacokinetics were also studied in 11 pediatric patients with detrusor overactivity associated with a neurological condition (e.g., spina bifida). these pediatric patients were on oxybutynin chloride tablets with total daily dose ranging from 7.5 mg to 15 mg (0.22 to 0.53 mg/kg). overall, most patients (86.9%) were taking a total daily oxybutynin chloride dose between 10 mg and 15 mg. sparse sampling technique was used to obtain serum samples. when all available data are normalized to an equivalent of 5 mg twice daily oxybutynin chloride, the mean pharmacokinetic parameters derived for r- and s-oxybutynin and r- and s-desethyloxybutynin are summarized in table 2 . 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 twice daily. table 2 mean ± sd r- and s-oxybutynin and r- and s-desethyloxybutynin pharmacokinetic parameters in children aged 5 to 15 following administration of 7.5 mg to 15 mg total daily dose of oxybutynin chloride tablets (n=11) all available data normalized to an equivalent of oxybutynin chloride tablets 5 mg bid or tid at steady state r-oxybutynin s-oxybutynin r-desethyloxybutynin s-desethyloxybutynin c max *(ng/ml) 6.1 ± 3.2 10.1 ± 7.5 55.4 ± 17.9 28.2 ± 10.0 t max (hr) 1.0 1.0 2.0 2.0 auc**(ng∙hr/ml) 19.8 ± 7.4 28.4 ± 12.7 238.8 ± 77.6 119.5 ± 50.7 *reflects cmax for pooled data **auc 0-end of dosing interval figure 2. mean steady-state (±sd) r-oxybutynin plasma concentrations following administration of total daily oxybutynin chloride tablet dose of 7.5 mg to 15 mg (0.22 mg/kg to 0.53 mg/kg) in children 5 to 15 years of age. – plot represents all available data normalized to the equivalent of oxybutynin chloride 5 mg bid or tid at steady state food effects data in the literature suggests that oxybutynin solution coadministered with food resulted in a slight delay in absorption and an increase in its bioavailability by 25% (n=18). 1 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 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. 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. graph 1 graph 2

ministered every 8 hours for 1 day in 23 healthy adult volunteers oxybutynin chloride steady-state pharmacokinetics were also studied in 11 pediatric patients with detrusor overactivity associated with a neurological condition (e.g., spina bifida). these pediatric patients were on oxybutynin chloride tablets with total daily dose ranging from 7.5 mg to 15 mg (0.22 to 0.53 mg/kg). overall, most patients (86.9%) were taking a total daily oxybutynin chloride dose between 10 mg and 15 mg. sparse sampling technique was used to obtain serum samples. when all available data are normalized to an equivalent of 5 mg twice daily oxybutynin chloride, the mean pharmacokinetic parameters derived for r- and s-oxybutynin and r- and s-desethyloxybutynin are summarized in table 2 . 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 twice daily. table 2 mean ± sd r- and s-oxybutynin and r- and s-desethyloxybutynin pharmacokinetic parameters in children aged 5 to 15 following administration of 7.5 mg to 15 mg total daily dose of oxybutynin chloride tablets (n=11) all available data normalized to an equivalent of oxybutynin chloride tablets 5 mg bid or tid at steady state r-oxybutynin s-oxybutynin r-desethyloxybutynin s-desethyloxybutynin c max *(ng/ml) 6.1 ± 3.2 10.1 ± 7.5 55.4 ± 17.9 28.2 ± 10.0 t max (hr) 1.0 1.0 2.0 2.0 auc**(ng∙hr/ml) 19.8 ± 7.4 28.4 ± 12.7 238.8 ± 77.6 119.5 ± 50.7 *reflects cmax for pooled data **auc 0-end of dosing interval figure 2. mean steady-state (±sd) r-oxybutynin plasma concentrations following administration of total daily oxybutynin chloride tablet dose of 7.5 mg to 15 mg (0.22 mg/kg to 0.53 mg/kg) in children 5 to 15 years of age. – plot represents all available data normalized to the equivalent of oxybutynin chloride 5 mg bid or tid at steady state food effects data in the literature suggests that oxybutynin solution coadministered with food resulted in a slight delay in absorption and an increase in its bioavailability by 25% (n=18). 1 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 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. 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.