NDC 72888-031 Oxybutynin Chloride

Oxybutynin Chloride

NDC Product Code 72888-031

NDC CODE: 72888-031

Proprietary Name: Oxybutynin Chloride What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Oxybutynin Chloride What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This is a long-acting form of oxybutynin that is used to treat overactive bladder and urinary conditions. It relaxes the muscles in the bladder to help decrease problems of urgency and frequent urination. Oxybutynin belongs to a class of drugs known as antispasmodics. This medication is also used to treat children 6 years of age and older who have an overactive bladder due to certain nerve disorders (e.g., spina bifida).

Product Characteristics

Color(s):
PINK (C48328 - LIGHT PINK TO PINK)
Shape: ROUND (C48348)
Size(s):
7 MM
8 MM
Imprint(s):
UPARROWHEAD13
UPARROWHEAD14
Score: 1

NDC Code Structure

  • 72888 - Advagen Pharma Limited

NDC 72888-031-01

Package Description: 100 TABLET, EXTENDED RELEASE in 1 BOTTLE

NDC Product Information

Oxybutynin Chloride with NDC 72888-031 is a a human prescription drug product labeled by Advagen Pharma Limited. The generic name of Oxybutynin Chloride is oxybutynin chloride. The product's dosage form is tablet, extended release and is administered via oral form.

Labeler Name: Advagen Pharma Limited

Dosage Form: Tablet, Extended Release - A solid dosage form containing a drug which allows at least a reduction in dosing frequency as compared to that drug presented in conventional dosage form.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Oxybutynin Chloride Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • OXYBUTYNIN CHLORIDE 10 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • CORN OIL (UNII: 8470G57WFM)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • METHACRYLIC ACID (UNII: 1CS02G8656)
  • ETHYL ACRYLATE (UNII: 71E6178C9T)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TALC (UNII: 7SEV7J4R1U)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • ISOPROPYL ALCOHOL (UNII: ND2M416302)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • SHELLAC (UNII: 46N107B71O)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • CORN OIL (UNII: 8470G57WFM)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • METHACRYLIC ACID (UNII: 1CS02G8656)
  • ETHYL ACRYLATE (UNII: 71E6178C9T)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TALC (UNII: 7SEV7J4R1U)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • ISOPROPYL ALCOHOL (UNII: ND2M416302)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • SHELLAC (UNII: 46N107B71O)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • AMMONIA (UNII: 5138Q19F1X)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cholinergic Muscarinic Antagonist - [EPC] (Established Pharmacologic Class)
  • Cholinergic Muscarinic Antagonists - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Advagen Pharma Limited
Labeler Code: 72888
FDA Application Number: ANDA214415 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 10-27-2020 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Oxybutynin Chloride Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Oxybutynin chloride extended-release tablets is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.Oxybutynin chloride extended-release tablets is 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 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 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 are available as 5,10 and 15 mg tablets for oral use:5 mg: Light pink to pink, round, film-coated tablets, imprinted with ‘Λ13’ in black ink on one side and plain on the other side.10 mg: Light pink to pink, round, film-coated tablets, imprinted with ‘Λ14’ in black ink on one side and plain on the other side.15 mg: White to off-white, round, film-coated tablets, imprinted with ‘Λ15’ in black ink on one side and plain on the other side.

4 Contraindications

Oxybutynin chloride extended-release tablets is contraindicated in patients with urinary retention, gastric retention and other severe decreased gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma.Oxybutynin chloride extended-release tablets is 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.

5.1 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.

6.1 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, Ditropan 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 release5 to 20 mg/day


n=199


%


Psychiatric Disorders  Insomnia3.05.5Nervous System Disorders  Headache7.58.0  Somnolence5.614.1  Dizziness5.016.6  Dysgeusia1.61.5 Eye Disorders  Vision blurred4.39.6  Dry eye3.12.5Respiratory, Thoracic and Mediastinal Disorders  Cough1.93.0  Oropharyngeal pain1.91.5  Dry throat1.72.5  Nasal dryness1.74.5Gastrointestinal Disorders  Dry mouth34.972.4  Constipation8.715.1  Diarrhea7.96.5  Dyspepsia4.56.0  Nausea4.511.6  Abdominal pain1.62.0  Vomiting1.31.5  Flatulence1.22.5  Gastro-esophageal reflux disease1.00.5Skin and Subcutaneous Tissue Disorders  Dry skin1.82.5  Pruritus1.31.5Renal and Urinary Disorders  Dysuria1.92.0  Urinary hesitation1.98.5  Urinary retention1.23.0General Disorders and Administration Site Conditions  Fatigue2.63.0Investigations  Residual urine volume


The bundled term residual urine volume consists of the preferred terms residual urine volume and residual urine volume increased.2.33.5The 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. 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 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.

Other

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 SummaryBased on animal data, oxybutynin is predicted to have a low probability of increasing the risk of adverse developmental effects above background risk.

Animal DataReproduction studies with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no evidence of impaired fertility or harm to the animal fetus.

System Components and PerformanceOxybutynin chloride extended-release tablets, USP uses an enteric coated hydrophilic hydrogel matrix to deliver oxybutynin chloride at controlled rate over approximately 24 hours by diffusion mechanism. The system comprises of a core, which contains the drug, rate controlling hydrogel and other excipients. The core is surrounded by a partially or complete pH dependent membrane. Hence, when the drug reaches the acidic medium, in stomach minimal drug release will occur and when it reaches an environment of pH 5.5 and above, the outer membrane will be dissolved exposing the inner core. This inner core will partially hydrate to form a gel layer and the drug release will occur via diffusion mechanism from a gel layer and subsequently through gel erosion.Meets USP Dissolution Method 4. FDA approved acceptance criteria differs from the USP acceptance criteria.

AbsorptionFollowing 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-OxybutyninC


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 5-15 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 DailyR-OxybutyninS-OxybutyninR- DesethyloxybutyninS- DesethyloxybutyninC


max (ng/mL)


0.7 ± 0.41.3 ± 0.87.8 ± 3.74.2 ± 2.3T


max (h)


5.05.05.05.0AUC (ng∙h/mL)12.8 ± 7.023.7 ± 14.4125.1 ± 66.773.6 ± 47.7Figure 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 tablets 5 mg once daily.

Food EffectsThe rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions.

DistributionOxybutynin 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.

MetabolismOxybutynin 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.

ExcretionOxybutynin 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 ProportionalityPharmacokinetic parameters of oxybutynin and desethyloxybutynin (Cmax and AUC) following administration of 5-20 mg of oxybutynin chloride extended-release tablets are dose proportional.

Use in Specific Populationss

PediatricThe 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).

GenderThere are no significant differences in the pharmacokinetics of oxybutynin in healthy male and female volunteers following administration of oxybutynin chloride extended-release tablets.

RaceAvailable 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.

Distributed by:


Advagen Pharma Ltd


666 Plainsboro Road


Suite 605


Plainsboro, NJ 08536, USA.


Manufactured by:


Rubicon Research Private Limited


Ambernath, Dist: Thane, 421506 India.

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 is 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 6-15 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 extended-release tablets, USP is an antispasmodic, muscarinic antagonist. Each oxybutynin chloride extended-release tablets, 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


22H


31NO


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 also contains the following inert ingredients: Hypromellose, Hydrogenated Vegetable Oil, Microcrystalline Cellulose, Lactose Monohydrate, Povidone, Colloidal Silicon Dioxide, Magnesium Stearate, Methacrylic Acid and ethyl acrylate co-polymer dispersion, Triethyl Citrate, Talc, Titanium dioxide, Polyethylene glycol/Macrogol, Iron Oxide Yellow non-irradiated, Isopropyl alcohol and Iron Red Oxide non-irradiated. The ink contains shellac glaze (modified), Black Iron Oxide non-irradiated, N-Butyl alcohol, propylene glycol and ammonium hydroxide.

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.

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.

14 Clinical Studies

Oxybutynin chloride extended-release tablets was 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


5Table 4: Number of Urge Urinary Incontinence Episodes Per Week (Study 1)Study 1nOxybutynin ERnPlacebo Mean Baseline3415.91620.9Mean (SD) Change from Baseline


Covariate adjusted mean with missing observations set to baseline values34-15.8 (8.9)16-7.6 (8.6)95% Confidence Interval for Difference(-13.6, -2.8)


The difference between Oxybutynin ER and placebo was statistically significant.(Oxybutynin ER - Placebo)Figure 3: Mean Change (±SD) in Urge Urinary Incontinence Episodes Per Week from Baseline (Study 1)Table 5: Number of Urge Urinary Incontinence Episodes Per Week (Study 2)Study 2nOxybutynin ERnoxybutyninMean Baseline5327.65223.0Mean (SD) Change from Baseline


Covariate adjusted mean with missing observations set to baseline values53-17.6 (11.9)52-19.4 (11.9)95% Confidence Interval for Difference(-2.8, 6.5)(Oxybutynin ER - oxybutynin)Figure 4: Mean Change (±SD) in Urge Urinary Incontinence Episodes Per Week from Baseline (Study 2)Table 6: Number of Urge Urinary Incontinence Episodes Per Week (Study 3)Study 3nOxybutynin ERnoxybutyninMean Baseline11118.911519.5Mean (SD) Change from Baseline


Covariate adjusted mean with missing observations set to baseline values111-14.5 (8.7)115-13.8 (8.6)95% Confidence Interval for Difference(-3.0, 1.6)


The difference between Oxybutynin Chloride Extended Release Tablets and oxybutynin fulfilled the criteria for comparable efficacy.(Oxybutynin ER - oxybutynin)Figure 5: Mean Change (±SD) in Urge Urinary Incontinence Episodes Per Week from Baseline (Study 3)

16 How Supplied/Storage And Handling

Oxybutynin chloride extended-release tablets, USP are available in three dosage strengths, 5 mg (light pink to pink), 10 mg (light pink to pink) and 15 mg (white to off-white) and imprinted on one side with ‘Λ13’ or ‘Λ14’ or ‘Λ15’ with black ink. Oxybutynin chloride extended-release tablets, USP are supplied in bottles of 100 tablets.5 mg                   100 count bottle                  NDC 72888-030-0110 mg                 100 count bottle                  NDC 72888-031-0115 mg                 100 count bottle                  NDC 72888-033-01

Storage And Handling

StorageStore 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 constipationHeat 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.For more information call Advagen Pharma Ltd, at 888-413-0949.All trademarks are the property of their respective owners.

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