NDC 70518-2331 Oxybutynin

Oxybutynin

NDC Product Code 70518-2331

NDC Code: 70518-2331

Proprietary Name: Oxybutynin 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 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.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE TO OFF-WHITE)
Shape: ROUND (C48348)
Size(s):
7 MM
Imprint(s):
256
Score: 1

NDC Code Structure

  • 70518 - Remedyrepack Inc.

NDC 70518-2331-0

Package Description: 90 TABLET, FILM COATED, EXTENDED RELEASE in 1 BOTTLE, PLASTIC

NDC Product Information

Oxybutynin with NDC 70518-2331 is a a human prescription drug product labeled by Remedyrepack Inc.. The generic name of Oxybutynin is oxybutynin. The product's dosage form is tablet, film coated, extended release and is administered via oral form.

Labeler Name: Remedyrepack Inc.

Dosage Form: Tablet, Film Coated, Extended Release - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a thin layer of a water-insoluble or water-soluble polymer; the tablet is formulated in such manner as to make the contained medicament available over an extended period of time following ingestion.

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 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.

  • ALGINIC ACID (UNII: 8C3Z4148WZ)
  • HYDROGENATED CASTOR OIL (UNII: ZF94AP8MEY)
  • HYPROMELLOSES (UNII: 3NXW29V3WO)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • METHACRYLIC ACID (UNII: 1CS02G8656)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • POVIDONE (UNII: FZ989GH94E)
  • TALC (UNII: 7SEV7J4R1U)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)

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.

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: Remedyrepack Inc.
Labeler Code: 70518
FDA Application Number: ANDA202332 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: 09-30-2019 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: 12-31-2020 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 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

Other

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).

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, USP are available as 5 mg, 10 mg and 15 mg tablets for oral use: Oxybutynin chloride extended-release tablets USP, 5 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "255" and plain on other side. Oxybutynin chloride extended-release tablets USP, 10 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "256" and plain on other side. Oxybutynin chloride extended-release tablets USP, 15 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "257" and plain on other side.

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.

The concomitant use of oxybutynin with other anticholinergic drugs or with other agents which produce dry mouth, constipation, somnolence (drowsiness), and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects. Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. This may be of concern for drugs with a narrow therapeutic index. Anticholinergic agents may also antagonize the effects of prokinetic agents, such as metoclopramide.Mean oxybutynin chloride plasma concentrations were approximately 2 fold higher when oxybutynin chloride extended-release 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. Cmax and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are coadministered.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.Please address medical inquiries to, MedicalAffairs@zydususa.com or Tel.: 1-877-993-8779This product's package insert may have been updated. For current package insert, please visit www.zydususa.comManufactured by:Cadila Healthcare LimitedAhmedabad, India.Distributed by:Zydus Pharmaceuticals (USA) Inc.Pennington, NJ 08534Rev.: 08/19

2.1 Adults

The recommended starting dose of oxybutynin chloride extended-release tablet is 5 mg 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 are 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).

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 symptom aggravation.

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, Oxybutynin chloride extended-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 -treated Adult Subjects in Five Double-blind, Controlled Clinical Trials of Oxybutynin chloride   


 2 The bundled term residual urine volume consists of the preferred terms residual urine volume and    


    residual urine volume increased.    System/Organ Class    Preferred Term Oxybutynin chloride extended-release tablets 5 to 30 mg/day n = 774 % Oxybutynin chloride immediate- release tablets 5 to 20 mg/day n = 199%  


Psychiatric Disorders Insomnia


3


5.5


Nervous System Disorders Headache


7.5


8


Somnolence


5.6


14.1


Dizziness


5


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


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


Nausea


4.5


11.6


Abdominal pain


1.6


2


Vomiting


1.3


1.5


Flatulence


1.2


2.5


Gastro-esophageal reflux disease


1


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


Urinary hesitation


1.9


8.5


Urinary retention


1.2


3


General Disorders and Administration Site Conditions Fatigue


2.6


3


I


nvestigations Residual urine volume


2 2.3


3.5


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 -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, QT interval prolongation;


Vascular Disorders: flushing, hypertension; S


kin 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.

8.1 Pregnancy

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

The safety and efficacy of oxybutynin chloride extended-release tablets were studied in 60 children in a 24 week, open-label, non-randomized trial. Patients were aged 6 to 15 years, all had symptoms of detrusor overactivity in association with a neurological condition (e.g. spina bifida), all used clean intermittent catheterization, and all were current users of oxybutynin chloride extended-release tablets. 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 H2O to 33 cm H2O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H2O) from 60% to 28%. The pharmacokinetics of oxybutynin chloride 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  are an antispasmodic, muscarinic antagonist. Each oxybutynin chloride Extended-release tablets 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, USP is a white crystalline, practically odorless powder with a molecular weight of 393.95. It is freely soluble in water and in alcohol, very soluble in methanol and in chloroform, soluble in acetone, slightly soluble in ether and very slightly soluble in hexane.Oxybutynin chloride extended-release tablet, USP also contains the following inactive ingredients: alginic acid, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, methacrylic acid copolymer dispersion, microcrystalline cellulose, povidone, talc and triethyl citrate.The product complies the USP Dissolution Test 8System Components and Performance Oxybutynin chloride extended-release tablet 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.

12.1 Mechanism Of Action

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


in vitro studies.

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

Absorption Following the first dose of oxybutynin chloride extended-release tablets,oxybutynin plasma concentrations rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours, minimizing fluctuations between peak and trough concentrations associated with oxybutynin. The relative bioavailabilities of R-and S-oxybutynin from oxybutynin chloride extended-release tabletsare 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 (0.6)


1.8 (1)


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 to 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 1Mean R-oxybutynin plasma concentrations following a single dose of oxybutynin chloride extended-release tablets10 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 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 Parameters (units) 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


5


5


5


AUC


(ng•h/mL)


12.8 ± 7


23.7 ± 14.4


125.1 ± 66.7


73.6 ± 47.7


Figure 2Mean steady state (± SD) R-oxybutynin plasma concentrations following administration of  5 to 20 mg oxybutynin chloride extended-release tablets  once daily in children aged 5 to 15. Plot represents all available data normalized to an equivalent of oxybutynin chloride extended-release tablets  5 mg once daily.Food Effects The rate and extent of absorption and metabolism of oxybutynin are similar under fed and fasted conditions. 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 (Cmax 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 to15 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  .

13.1 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 normalizationof body surface area.Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Sacchar omyces 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  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%) and female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry criteria required that patients have urge or mixed incontinence (with a predominance of urge) as evidenced by ≥ 6 urge incontinence episodes per week and ≥ 10 micturitions per day. Study 1 was a fixed-dose escalation design, whereas the other two studies used a dose-adjustment design in which each patient's final dose was adjusted to a balance between improvement of incontinence symptoms and tolerability of side effects. All three studies included patients known to be responsive to oxybutynin or other anticholinergic medications, and these patients were maintained on a final dose for up to 2 weeks. The efficacy results for the three controlled trials are presented in the following tables and figures.

16 How Supplied/Storage And Handling

Oxybutynin Chloride Extended-release Tablets USP, 5 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "255" and plain on other side and are supplied as follows:NDC 68382-255-06 in bottle of 30 tablets with child-resistant closureNDC 68382-255-14 in bottle of 60 tablets with child-resistant closureNDC 68382-255-16 in bottle of 90 tablets with child-resistant closureNDC 68382-255-01 in bottle of 100 tabletsNDC 68382-255-05 in bottle of 500 tabletsNDC 68382-255-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tabletsOxybutynin Chloride Extended-release Tablets USP, 10 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "256" and plain on other side and are supplied as follows:NDC 68382-256-06 in bottle of 30 tablets with child-resistant closureNDC 68382-256-14 in bottle of 60 tablets with child-resistant closureNDC 68382-256-16 in bottle of 90 tablets with child-resistant closureNDC 68382-256-01 in bottle of 100 tabletsNDC 68382-256-05 in bottle of 500 tabletsNDC 68382-256-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tabletsOxybutynin Chloride Extended-release Tablets USP, 15 mg are white to off-white, round, beveled-edged, biconvex, coated-tablets debossed on one side with "257" and plain on other side and are supplied as follows:NDC 68382-257-06 in bottle of 30 tablets with child-resistant closureNDC 68382-257-14 in bottle of 60 tablets with child-resistant closureNDC 68382-257-16 in bottle of 90 tablets with child-resistant closureNDC 68382-257-01 in bottle of 100 tabletsNDC 68382-257-05 in bottle of 500 tabletsNDC 68382-257-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tabletsStorageStore at 20° to 25°C (68° to 77°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 hydrated polymer system of the tablet is not rigid and is expected to be broken up by normal peristalsis in the GI tract. The biologically inert components of the tablet may occasionally remain intact during GI transit and will be eliminated in the feces as a soft, hydrated mass. Oxybutynin chloride extended-release tablets should be taken at approximately the same time each day.

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