OXYBUTYNIN CHLORIDE EXTENDED RELEASE

Main information

  • Trade name:
  • OXYBUTYNIN CHLORIDE EXTENDED RELEASE- oxybutynin chloride tablet, extended release
  • Composition:
  • OXYBUTYNIN CHLORIDE 5 mg
  • Administration route:
  • ORAL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • OXYBUTYNIN CHLORIDE  EXTENDED RELEASE- oxybutynin chloride tablet, extended release
    United States
  • Language:
  • English

Therapeutic information

  • Therapeutic indications:
  • 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 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. Pregnancy Category B. There are no adequate and well-controlled studies using Oxybutynin chloride extended-releas
  • Product summary:
  • Oxybutynin chloride extended-release tablets 5 mg are round, biconvex, white coated tablets imprinted in black ink with "270" on one side and "KU" on the other side. They are supplied as follows: Bottles of 30 Tablets               NDC 62175-270-32 Bottles of 100 Tablets             NDC 62175-270-37 Bottles of 500 Tablets             NDC 62175-270-41 Bottles of 1000 Tablets           NDC 62175-270-43 Oxybutynin chloride extended-release tablets 10 mg are round, biconvex, white coated tablets imprinted in black ink with "271" on one side and "KU" on the other side. They are supplied as follows: Bottles of 30 Tablets               NDC 62175-271-32 Bottles of 100 Tablets             NDC 62175-271-37 Bottles of 500 Tablets             NDC 62175-271-41 Bottles of 1000 Tablets           NDC 62175-271-43 Oxybutynin chloride extended-release tablets 15 mg are round, biconvex, white coated tablets imprinted in black ink with "272" on one side and "KU" on the other side. They are supplied as follows: Bottles of 30 Tablets               NDC 62175-272-32 Bottles of 100 Tablets             NDC 62175-272-37 Bottles of 500 Tablets             NDC 62175-272-41 Bottles of 1000 Tablets           NDC 62175-272-43 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.

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Authorization number:
  • 43353-285-30, 43353-285-53, 43353-285-60
  • Last update:
  • 26-05-2019

Summary of Product characteristics: dosage, interactions, side effects

OXYBUTYNIN CHLORIDE EXTENDED RELEASE- oxybutynin chloride tablet, extended

release

Aphena Pharma Solutions - Tennessee, LLC

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use Oxybutynin chloride extended-release

tablets safely and effectively. See full prescribing information for Oxybutynin chloride extended-release

tablets.

Oxybutynin chloride extended-release tablets for oral use

Initial U.S. Approval: 1975

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. (1)

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). (1)

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)

Adults: Start with 5 mg or 10 mg, once daily at approximately the same time every day. Dose should not exceed 30 mg

per day. ( 2.1)

Pediatric patients (6 years of age or older): Start with 5 mg, once daily at approximately the same time every day.

Dose should not exceed 20 mg per day. ( 2.2)

DOSAGE FORMS AND STRENGTHS

Extended release tablets 5 mg, 10 mg and 15 mg (3)

CONTRAINDICATIONS

Urinary retention (4)

Gastric Retention (4)

Uncontrolled narrow angle glaucoma (4)

Known hypersensitivity to Oxybutynin chloride extended-release tablets, oxybutynin or any component of Oxybutynin

chloride extended-release tablets (4)

WARNINGS AND PRECAUTIONS

Angioedema: Angioedema has been reported with oxybutynin. If symptoms of angioedema occur,

discontinue Oxybutynin chloride extended-release tablets immediately and initiate appropriate therapy. ( 5.1)

Central Nervous System (CNS) effects: CNS effects have been reported with oxybutynin. If patient experiences

anticholinergic CNS effects, consider dose adjustment or discontinuation of Oxybutynin chloride extended-release

tablets. ( 5.2)

Use with caution due to aggravation of symptoms:

Pre-existing dementia in patients treated with cholinesterase inhibitors (5.2),

Parkinson's disease (5.2),

Myasthenia gravis (5.3), and

Decreased gastrointestinal motility in patients with autonomic neuropathy. (5.4)

Urinary Retention: Use with caution in patients with clinically significant bladder outflow obstruction because of the risk

of urinary retention (5.5)

Gastrointestinal Adverse Reactions: Use with caution in patients with gastrointestinal obstructive disorders or

decreased intestinal motility due to risk of gastric retention. Use with caution in patients with gastroesophageal reflux or

in patients concurrently taking drugs that can exacerbate esophagitis. (5.6)

ADVERSE REACTIONS

The most common (incidence ≥5%) adverse reactions were dry mouth, constipation, diarrhea, headache, somnolence, and

dizziness. (6)

To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-

800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Co-administration with other anticholinergic drugs may increase the frequency and/or severity of anticholinergic-like

effects. (7)

Co-administration with strong cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole) increases the systemic

exposure of oxybutynin. (7)

USE IN SPECIFIC POPULATIONS

Pediatric Use: 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 years. (8.4)

Renal or Hepatic Impairment: There have been no studies conducted in patients with renal or hepatic impairment. ( 8.6,

8.7)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 10/2016

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Adults

2.2 Pediatric Patients Aged 6 Years of Age and Older

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Angioedema

5.2 Central Nervous System Effects

5.3 Worsening of Symptoms of Myasthenia Gravis

5.4 Worsening of Symptoms of Decreased Gastrointestinal Motility in Patients with Autonomic

Neuropathy

5.5 Urinary Retention

5.6 Gastrointestinal Adverse Reactions

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Storage

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

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 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 are available as 5, 10 and 15 mg tablets for oral use:

5 mg: White, round, biconvex tablet with "270" printed on one side and "KU" printed on the other side

with black ink.

10 mg: White, round, biconvex tablet with "271" printed on one side and "KU" printed on the other side

with black ink.

15 mg: White, round, biconvex tablet with "272" printed on one side and "KU" printed on the other side

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.

Sections or subsections omitted from the full prescribing information are not listed.

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.

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 affect 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 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 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 chloride extended-release

tablets

5 to 30 mg/day

n = 774

%

Oxybutynin chloride IR

5 to 20 mg/day

n = 199

%

Psychiatric Disorders

Insomnia

Nervous System Disorders

Headache

Somnolence

14.1

Dizziness

16.6

Dysgeusia

Eye Disorders

Vision blurred

Dry eye

Respiratory, Thoracic and Mediastinal Disorders

Cough

Oropharyngeal pain

Dry throat

Nasal dryness

Gastrointestinal Disorders

Dry mouth

34.9

72.4

Constipation

15.1

Diarrhea

Dyspepsia

Nausea

11.6

Abdominal pain

Vomiting

*

Flatulence

Gastro-esophageal reflux

disease

Skin and Subcutaneous Tissue Disorders

Dry skin

Pruritus

Renal and Urinary Disorders

Dysuria

Urinary hesitation

Urinary retention

General Disorders and Administration Site Conditions

Fatigue

Investigations

Residual urine volume

The discontinuation rate due to adverse reactions was 4.4% with Oxybutynin chloride extended-release

tablets compared to 0% with Oxybutynin chloride 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; 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.

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

IR = immediate release

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

volume increased.

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., C

and 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

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 6–15 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

O to 33 cm H

O, and a reduction in the percentage of patients demonstrating

uninhibited detrusor contractions (of at least 15 cm H

O) 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. Activated charcoal as well as 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

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 also contain the following inert ingredients: lactose,

mannitol, dextrose, tartaric acid, colloidal silicon dioxide, magnesium stearate, cellulose acetate,

polyethylene glycol, titanium dioxide, triacetin, black iron oxide, propylene glycol, hypromellose.

System Components and Performance

Oxybutynin chloride extended-release tablets 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 core surrounded by a semipermeable membrane. The

unitary tablet core is composed of the drug and excipients (including the osmotically active

components). There is a precision-laser drilled orifice in the semipermeable membrane on the 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 osmotic components to

expand. This expansion pushes the 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 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.

USP Drug Release Test 3.

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 vitro studies.

12.2 Pharmacodynamics

In patients with conditions characterized by involuntary bladder contractions, cystometric studies have

demonstrated that oxybutynin increases bladder (vesical) capacity, diminishes the frequency of

uninhibited contractions of the detrusor muscle, and delays the initial desire to void.

12.3 Pharmacokinetics

Absorption

Following the first dose of Oxybutynin chloride extended-release tablets, oxybutynin plasma

concentrations rise for 4 to 6 hours; thereafter steady concentrations are maintained for up to 24 hours,

minimizing fluctuations between peak and trough concentrations associated with oxybutynin.

The relative bioavailabilities of R- and S-oxybutynin from Oxybutynin chloride extended-release

tablets are 156% and 187%, respectively, compared with oxybutynin. The mean pharmacokinetic

parameters for R- and S-oxybutynin are summarized in Table 2. The plasma concentration-time profiles

for R- and S-oxybutynin are similar in shape; Figure 1 shows the profile for R-oxybutynin.

Table 2: Mean (SD) R- and S-Oxybutynin

Pharmacokinetic Parameters Following a Single

Dose of Oxybutynin chloride extended-release

tablets 10 mg (n=43)

Parameters (units)

R-Oxybutynin S-Oxybutynin

(ng/mL)

(0.6)

(1.0)

12.7

(5.4)

11.8 (5.3)

13.2

(6.2)

12.4 (6.1)

(ng·h/mL) 18.4

(10.3)

34.2 (16.9)

(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

Daily

R-Oxybutynin S-Oxybutynin R- Desethyloxybutynin S- Desethyloxybutynin

(0–48)

(ng/mL)

0.7 ± 0.4

1.3 ± 0.8

7.8 ± 3.7

4.2 ± 2.3

AUC (ng·h/mL) 12.8 ± 7.0

23.7 ± 14.4

125.1 ± 66.7

73.6 ± 47.7

Figure 2: Mean steady state (± SD) R-oxybutynin plasma concentrations following administration

of 5 to 20 mg Oxybutynin chloride extended-release tablets once daily in children aged 5–15. 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 (C

and 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

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 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 and figures.

Number of Urge Urinary Incontinence Episodes Per Week

Study 1

n

Oxybutynin chloride extended-release

tablets

n

Placebo

Mean Baseline

15.9

20.9

Mean (SD) Change from Baseline

-15.8 (8.9)

-7.6

(8.6)

95% Confidence Interval for

Difference

(-13.6, -2.8)

(Oxybutynin chloride extended-release tablets- Placebo)

Study 2

n

Oxybutynin chloride extended-release

tablets

n oxybutynin

Mean Baseline

27.6

23.0

Mean (SD) Change from Baseline

-17.6 (11.9)

-19.4

(11.9)

95% Confidence Interval for

Difference

(-2.8, 6.5)

(Oxybutynin chloride extended-release tablets- oxybutynin)

Study 3

n

Oxybutynin chloride extended-release

tablets

n

oxybutynin

Mean Baseline

18.9

19.5

Mean (SD) Change from Baseline

-14.5 (8.7)

115 -13.8 (8.6)

95% Confidence Interval for

Difference

(-3.0, 1.6)

(Oxybutynin chloride extended-release tablets- oxybutynin)

Covariate adjusted mean with missing observations set to baseline values

The difference between Oxybutynin chloride extended-release tabletsand placebo was statistically significant.

Covariate adjusted mean with missing observations set to baseline values

Covariate adjusted mean with missing observations set to baseline values

The difference between Oxybutynin chloride extended-release tabletsand oxybutynin fulfilled the criteria for

comparable efficacy.

16 HOW SUPPLIED/STORAGE AND HANDLING

Oxybutynin chloride extended-release tablets 5 mg are round, biconvex, white coated tablets imprinted

in black ink with "270" on one side and "KU" on the other side.

They are supplied as follows:

Bottles of 30 Tablets NDC 62175-270-32

Bottles of 100 Tablets NDC 62175-270-37

Bottles of 500 Tablets NDC 62175-270-41

Bottles of 1000 Tablets NDC 62175-270-43

Oxybutynin chloride extended-release tablets 10 mg are round, biconvex, white coated tablets imprinted

in black ink with "271" on one side and "KU" on the other side.

They are supplied as follows:

Bottles of 30 Tablets NDC 62175-271-32

Bottles of 100 Tablets NDC 62175-271-37

Bottles of 500 Tablets NDC 62175-271-41

Bottles of 1000 Tablets NDC 62175-271-43

Oxybutynin chloride extended-release tablets 15 mg are round, biconvex, white coated tablets imprinted

in black ink with "272" on one side and "KU" on the other side.

They are supplied as follows:

Bottles of 30 Tablets NDC 62175-272-32

Bottles of 100 Tablets NDC 62175-272-37

Bottles of 500 Tablets NDC 62175-272-41

Bottles of 1000 Tablets NDC 62175-272-43

16.1 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.

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 1-844-834-0530.

Distributed by:

Kremers Urban Pharmaceuticals Inc.,

a subsidiary of Lannett Company, Inc.

Seymour, IN 47274

Made in the USA

CIA72763K

Rev. 10/2016

Repackaging Information

Please reference the How Supplied section listed above for a description of individual tablets. This

drug product has been received by Aphena Pharma - TN in a manufacturer or distributor packaged

configuration and repackaged in full compliance with all applicable cGMP regulations. The package

configurations available from Aphena are listed below:

Count

5 mg

43353-285-30

43353-285-53

43353-285-60

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-

resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by:

Cookeville, TN 38506

20171020JH

PRINCIPAL DISPLAY PANEL - 5 mg

NDC 43353-285 - Oxybutynin Chloride ER 5mg - Rx Only

OXYBUTYNIN CHLORIDE EXTENDED RELEASE

oxybutynin chloride tablet, extended release

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:43353-28 5(NDC:6 2175-270 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

O XYBUTYNIN CHLO RIDE (UNII: L9 F3D9 RENQ) (OXYBUTYNIN - UNII:K9 P6 MC70 9 2)

OXYBUTYNIN CHLORIDE

5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

ANHYDRO US LACTO SE (UNII: 3SY5LH9 PMK)

LACTO SE MO NO HYDRATE (UNII: EWQ57Q8 I5X)

MANNITO L (UNII: 3OWL53L36 A)

ANHYDRO US DEXTRO SE (UNII: 5SL0 G7R0 OK)

Aphena Pharma Solutions - Tennessee, LLC

TARTARIC ACID (UNII: W48 8 8 I119 H)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE ACETATE (UNII: 3J2P0 7GVB6 )

PO LYETHYLENE GLYCO L 4 0 0 (UNII: B6 9 78 9 4SGQ)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

HYPRO MELLO SE 2 2 0 8 ( 10 0 MPA.S) (UNII: B1QE5P712K)

TRIACETIN (UNII: XHX3C3X6 73)

Product Characteristics

Color

white

S core

no sco re

S hap e

ROUND

S iz e

Flavor

Imprint Code

KU;270

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:43353-28 5-30

30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/0 2/20 17

2

NDC:43353-28 5-53

6 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/0 2/20 17

3

NDC:43353-28 5-6 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/0 2/20 17

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 50 3

0 3/0 1/20 0 9

Labeler -

Aphena Pharma Solutions - T ennessee, LLC (128385585)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Aphena Pharma So lutio ns - Tennessee, LLC

128 38 558 5

REPACK(43353-28 5)

Revised: 10/2017