OXYBUTYNIN CHLORIDE EXTENDED RELEASE- oxybutynin chloride tablet, extended release

Oxybutynin Chloride by

Drug Labeling and Warnings

Oxybutynin Chloride by is a Prescription medication manufactured, distributed, or labeled by Drug Ocean LLC, Unique Pharmaceutical Laboratories. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    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.

    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).

  • 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.

    2.1 Adults

    The recommended starting dose of oxybutynin chloride extended-release tablets are 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 tablets 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).

  • 3 DOSAGE FORMS AND STRENGTHS

    Oxybutynin chloride extended-release tablets USP is available as 5 mg tablets for oral use:
    5 mg: Pale yellow colored, round, biconvex tablets with orifice and "P 5" imprinted with black ink.

  • 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 angioedema.

  • 5 WARNINGS AND PRECAUTIONS

    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 Adverse Reactions (6)] . 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 tablets 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 Contraindications (4)] .

    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 Contraindications (4)] .

    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.

  • 6 ADVERSE REACTIONS

    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 chloride immediate release tablets (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 Chloride
    Extended-Release
    Tablets
    5 to 30 mg/day
    n = 774 %
    		Oxybutynin Chloride
    IR 1Tablets
    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 2
    		2.3
    		3.5
    1IR=immediate release
    2The bundled term residual urine volume consists of the preferred terms residual urine volume and residual urine volume increased.

    The discontinuation rate due to adverse reactions was 4.4% with oxybutynin chloride extended-release tablets compared to 0% with oxybutynin chloride immediate release tablets. 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. In one reported case, concomitant use of oxybutynin with carbamazepine and dantrolene was associated with adverse events of vomiting, drowsiness, confusion, unsteadiness, slurred speech and nystagmus, suggestive of carbamazepine toxicity.

  • 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 plasma concentrations were approximately 2 fold higher when oxybutynin chloride extended-release tablets were 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 maxand AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary
    There are no adequate data on oxybutynin chloride extended-release tablets use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

    In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.


    8.2 Lactation

    Risk Summary
    There are no data on the presence of oxybutynin in human milk, the effects on the breastfed infant, or the effects of oxybutynin chloride extended-release tablets on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxybutynin chloride extended-release tablets and any potential adverse effects on the breastfed child from oxybutynin chloride extended-release tablets or from the underlying maternal condition.

    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 6-15 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 2O to 33 cm H 2O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H 2O) from 60% to 28%.

    The pharmacokinetics of oxybutynin chloride extended-release tablets in these patients were consistent with those reported for adults [see Clinical Pharmacology (12.3)] .

    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.

  • 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.

  • 11 DESCRIPTION

    Oxybutynin chloride USP is an antispasmodic, muscarinic antagonist. Each oxybutynin chloride extended-release tablet USP contains 5 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-butynylphenylcyclohexylglycolate hydrochloride. The empirical formula of oxybutynin chloride is C 22H 31NO 3HCl.

    Its structural formula is:

    structure

    Oxybutynin chloride USP 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 tablet, USP also contains the following inert ingredients: polyethylene oxide, hypromellose, sodium chloride, butylated hydroxytoluene, ferric oxide (yellow), ferric oxide (red), ferric oxide (black), colloidal silicon dioxide, magnesium stearate, cellulose acetate, polyethylene glycol, titanium dioxide, lactose monohydrate, triacetin, shellac, and propylene glycol.

    System Components and Performance
    Oxybutynin chloride extended-release tablets USP uses osmotic pressure to deliver oxybutynin chloride at a controlled rate over approximately 24 hours. The system, which resembles a conventional tablet in appearance, comprises an osmotically active bilayer core surrounded by a semipermeable membrane. The bilayer core is composed of a drug layer containing the drug and excipients, and a push layer containing osmotically active components. There is a precision-laser drilled orifice in the semipermeable membrane on the drug-layer side of the tablet. In an aqueous environment, such as the gastrointestinal tract, water permeates through the membrane into the tablet core, causing the drug to go into suspension and the push layer to expand. This expansion pushes the suspended drug out through the orifice. The semipermeable membrane controls the rate at which water permeates into the tablet core, which in turn controls the rate of drug delivery. The controlled rate of drug delivery into the gastrointestinal lumen is thus independent of pH or gastrointestinal motility. The function of oxybutynin chloride extended-release tablets depends on the existence of an osmotic gradient between the contents of the bilayer core and the fluid in the gastrointestinal tract. Since the osmotic gradient remains constant, drug delivery remains essentially constant. The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the feces as an insoluble shell.
    Product meets USP Dissolution Test 6

  • 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 vitrostudies.

    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)(ngh/mL)
     18.4      (10.3)
    34.2    (16.9)

    AUC inf(ngh/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 5-15 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 5-15 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)

    T max(h)

    AUC (ngh/mL)
    0.7 ± 0.4

     5.0

     12.8 ± 7.0
    1.3 ± 0.8

     5.0

     23.7 ± 14.4
    7.8 ± 3.7

    5.0

     125.1 ± 66.7
    4.2 ± 2.3

    5.0

     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 5-15. Plot represents all available data normalized to an equivalent of Oxybutynin Chloride Extended-Release Tablet 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 maxand AUC) following administration of 5-20 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 5-15 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.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis
    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.

    Mutagenesis
    Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae,and Salmonella typhimuriumtest systems.

    Impairment of Fertility
    No impairment of fertility was seen in rats at dosages up to 75 mg/kg/day (24 times the MRHD on a mg/m 2basis) when administered for 2 weeks prior to mating in females and for 9 weeks prior to mating in males.

  • 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 4, 5, and 6 and Figures 3, 4, and 5.


    Table 4: Number of Urge Urinary Incontinence Episodes Per Week (Study 1)
    Study 1
    		n          
    		Oxybutynin chloride
    extended-release tablets
    		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 chloride extended-
    release tablets – Placebo)

    *The difference between Oxybutynin chloride extended-release tablets and placebo was statistically significant.

    †Covariate adjusted mean with missing observations set to baseline values



    Figure 3: Mean Change (± SD) in Urge Urinary Incontinence Episodes Per Week from Baseline (Study 1)


    Figure 3


    *The difference between Oxybutynin chloride extended-release tablets and placebo was statistically significant.
    Table 5: Number of Urge Urinary Incontinence Episodes Per Week (Study 2)


    Study 2
    		n
    		Oxybutynin chloride
    extended-release tablets
    		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 chloride
    extended-release
    tablets – oxybutynin)


     †Covariate adjusted mean with missing observations set to baseline values

    Figure 4: Mean Change (±SD) in Urge Urinary Incontinence Episodes Per Week from Baseline (Study 2)

    Figure 4


    Table 6: Number of Urge Urinary Incontinence Episodes Per Week (Study 3)



    Study 3
    		n         
    		Oxybutynin chloride
    extended-release tablets
    		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 (Oxybutynin
    chloride extended-release
    tablets – oxybutynin)
    		(-3.0, 1.6) **

    **The difference between Oxybutynin chloride extended-release tablets and oxybutynin fulfilled the criteria for comparable efficacy.

    †Covariate adjusted mean with missing observations set to baseline values


    Figure 5: Mean Change (±SD) in Urge Urinary Incontinence Episodes Per Week from
    Baseline (Study 3)


    Figure 5

    **The difference between Oxybutynin chloride extended-release tablets and oxybutynin fulfilled the criteria for comparable efficacy.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    Oxybutynin chloride extended-release tablets USP is available in 5 mg (pale yellow round biconvex with orifice) and is imprinted on one side with "P 5" with black ink. Oxybutynin chloride extended-release tablets USP are supplied in bottles of 100 and 500 tablets.

    5 mg         100 count bottle               NDC: 70985-021-01
    5 mg         500 count bottle               NDC 70985-021-02

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

    Keep out of reach of children.

  • 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. The medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell is eliminated from the body; patients should not be concerned if they occasionally notice in their stool something that looks like a tablet.
    • Oxybutynin chloride extended-release tablets should be taken at approximately the same time each day.

    For more information call Drug Ocean LLC at 1-844-200-6566.

    Manufactured by:Unique Pharmaceutical Laboratories
    (A Div. of J. B. Chemicals & Pharmaceuticals Ltd.)
    Mumbai, 400 030, India.

    Distributed by:

    Company Logo

    Drug Ocean LLC
    1 Bridge Plaza, North Central Road,
    6th Floor, Suite 675, Fort Lee, NJ 07024

    ORG 10/2023

    XXXXXX

  • PRINCIPAL DISPLAY PANEL


    ———PRINCIPAL DISPLAY PANEL - 5 mg———

    Drug Ocean NDC: 70985-021-01

    Oxybutynin Chloride
    Extended-Release Tablets USP
    5 mg

    Rx Only
    100 Tablets

    5 mg tabs- 100

  • PRINCIPAL DISPLAY PANEL

    ———PRINCIPAL DISPLAY PANEL - 5 mg———

    Drug Ocean NDC: 70985-021-02

    Oxybutynin Chloride
    Extended-Release Tablets USP
    5 mg

    Rx Only
    500 Tablets

    5 mg tab-500

  • INGREDIENTS AND APPEARANCE
    OXYBUTYNIN CHLORIDE  EXTENDED RELEASE
    oxybutynin chloride tablet, extended release
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 70985-021
    Route of AdministrationORAL
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    OXYBUTYNIN CHLORIDE (UNII: L9F3D9RENQ) (OXYBUTYNIN - UNII:K9P6MC7092) OXYBUTYNIN CHLORIDE5 mg
    Inactive Ingredients
    Ingredient NameStrength
    POLYETHYLENE OXIDE 7000000 (UNII: G3MS6M810Y)  
    POLYETHYLENE OXIDE 200000 (UNII: 11628IH70O)  
    HYPROMELLOSE 2910 (3 MPA.S) (UNII: 0VUT3PMY82)  
    SODIUM CHLORIDE (UNII: 451W47IQ8X)  
    BUTYLATED HYDROXYTOLUENE (UNII: 1P9D0Z171K)  
    FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
    FERROSOFERRIC OXIDE (UNII: XM0M87F357)  
    SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
    MAGNESIUM STEARATE (UNII: 70097M6I30)  
    CELLULOSE ACETATE (UNII: 3J2P07GVB6)  
    POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
    TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
    LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
    TRIACETIN (UNII: XHX3C3X673)  
    SHELLAC (UNII: 46N107B71O)  
    HYPROMELLOSE 2910 (6 MPA.S) (UNII: 0WZ8WG20P6)  
    PROPYLENE GLYCOL (UNII: 6DC9Q167V3)  
    Product Characteristics
    Coloryellow (pale yellow) Scoreno score
    ShapeROUNDSize7mm
    FlavorImprint Code P5
    Contains    
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 70985-021-01100 in 1 BOTTLE; Type 0: Not a Combination Product10/05/2023
    2NDC: 70985-021-02500 in 1 BOTTLE; Type 0: Not a Combination Product10/05/2023
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA20612110/05/2023
    Labeler - Drug Ocean LLC (080381835)
    Establishment
    NameAddressID/FEIBusiness Operations
    Unique Pharmaceutical Laboratories650434645manufacture(70985-021)
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