Oxybutynin

ANTUROL (oxybutynin) gel 3% is a muscarinic receptor antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency [see Clinical Studies].

Oxybutynin is a prescription medication used to treat overactive bladder.  Oxybutynin belongs to a group of drugs called antispasmodics, which help to relax the bladder muscle. 

This medication comes in tablet (immediate and extended release forms), gel, liquid (syrup) or transdermal (patch) form, and is taken up to 4 times daily, with or without food.  It is also available over-the-counter, in a patch formulation.  Do not chew, divide, or break the extended release form of this medication (ditropan XL tablets).  Swallow tablets whole.

Common side effects of oxybutynin include dry mouth, constipation, and nausea.  Oxybutynin can also cause blurred vision, drowsiness, and dizziness.  Do not drive or operate heavy machinery until you know how oxybutynin affects you.

Serious side effects have been reported with oxybutynin.  See the "oxybutynin precautions" section.  Common side effects of oxybutynin include the following:

Oral (immediate release or XL tablet, liquid):

• Dry mouth
• Dizziness
• Drowsiness
• Constipation
• Nausea
• Blurred vision

Topical gel:

• Reaction at application site (redness, itching, irritation, pain, rash)
• May also experience side effects listed for the oral formulation

Transdermal:

• Localized redness and swelling, itching
• Diarrhea
• May also experience side effects listed for the oral formulation

This is not a complete list of oxybutynin side effects.  Ask your doctor or pharmacist for more information.  Tell your doctor if you have any side effect that bothers you or that does not go away.  Call your doctor for medical advice about side effects.  You may report side effects to the FDA at 1-800-FDA-1088.

Take this medication exactly as prescribed by your doctor.  Follow the directions on your prescription label carefully. 

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Oral (immediate release, extended release)

The recommended dose of oxybutynin for the treatment of overactive bladder is one 5 mg tablet two to three times a day.  The maximum recommended dose is one 5 mg tablet four times a day.

The recommended dose of Ditropan XL (oxybutynin chloride) for the treatment of overactive bladder is 5 to 10 mg once daily initially, followed by increases in the dosage by 5 mg at weekly intervals.  The maximum recommended dose is 30 mg once daily.

Topical:

The recommended dose of Gelnique 3% (oxybutynin) for the treatment of overactive bladder is 3 pumps (84 mg) once daily.  The recommended dose of Gelnique 10% (oxybutynin) for the treatment of overactive bladder is 1 sachet (100 mg/g) once daily.

Transdermal:

The recommended dose of Oxytrol (oxybutynin) is one 3.9 mg/day patch twice weekly (every 3-4 days).

In the U.S.

• Ditropan
• Ditropan XL

Available Dosage Forms:

• Tablet, Extended Release
• Tablet
• Syrup

Therapeutic Class: Urinary Antispasmodic

Pharmacologic Class: Oxybutynin

Each scored Oxybutynin chloride tablet contains 5 mg of Oxybutynin chloride. Chemically, Oxybutynin chloride is d,l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate hydrochloride. The empirical formula of Oxybutynin chloride is C22H31NO3•HCl. The structural formula appears below:

Oxybutynin chloride is a white crystalline solid with a molecular weight of 393.95. It is readily soluble in water and acids, but relatively insoluble in alkalis.

Oxybutynin Chloride Tablets also contain: FD&C Blue #1 aluminum lake, magnesium stearate, microcrystalline cellulose, and pregelatinized starch.

Oxybutynin Chloride Tablets are for oral administration.

Therapeutic Category: Antispasmodic, anticholinergic.

Central Nervous System Effects

Oxybutynin is associated with anticholinergic central nervous system (CNS) effects (see ADVERSE REACTIONS). 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. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

Oxybutynin chloride should be used with caution in patients with pre-existing dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

General

Oxybutynin chloride should be used with caution in the frail elderly, in patients with hepatic or renal impairment, and in patients with myasthenia gravis.

Oxybutynin chloride may aggravate the symptoms of hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, hiatal hernia, tachycardia, hypertension, myasthenia gravis, and prostatic hypertrophy.

Urinary Retention

Oxybutynin chloride should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention (see CONTRAINDICATIONS).

Gastrointestinal Disorders

Oxybutynin chloride should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention (see CONTRAINDICATIONS).

Administration of Oxybutynin chloride to patients with ulcerative colitis may suppress intestinal motility to the point of producing a paralytic ileus and precipitate or aggravate toxic megacolon, a serious complication of the disease.

Oxybutynin chloride, 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 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.

Information for Patients

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 edema of the tongue, edema of the laryngopharynx, or difficulty breathing.

Patients should be informed that heat prostration (fever and heat stroke due to decreased sweating) can occur when anticholinergics such as Oxybutynin chloride are administered in the presence of high environmental temperature.

Because anticholinergic agents such as Oxybutynin may produce drowsiness (somnolence), or blurred vision, patients should be advised to exercise caution.

Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as Oxybutynin.

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.

Mean Oxybutynin chloride plasma concentrations were approximately 3 to 4 fold higher when Oxybutynin chloride 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., Cmax and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.

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 surface area.

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

Reproduction studies using Oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no definite evidence of impaired fertility.

Pregnancy

Reproduction studies using Oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no definite evidence of impaired fertility or harm to the animal fetus. The safety of Oxybutynin chloride administered to women who are or who may become pregnant has not been established. Therefore, Oxybutynin chloride should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Oxybutynin chloride is administered to a nursing woman.

Pediatric Use

The safety and efficacy of Oxybutynin chloride administration have been demonstrated for pediatric patients 5 years of age and older (see DOSAGE AND ADMINISTRATION).

The safety and efficacy of Oxybutynin chloride tablets were studied in 30 children in a 24-week, open-label trial. Patients were aged 5 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. Study results demonstrated that the administration of Oxybutynin chloride was associated with improvement in clinical and urodynamic parameters.

At total daily doses ranging from 5 mg to 15 mg, treatment with Oxybutynin chloride tablets was associated with an increase from baseline in mean urine volume per catheterization from 122 mL to 145 mL, an increase from baseline in mean urine volume after morning awakening from 148 mL to 168 mL, and an increase from baseline in the mean percentage of catheterizations without a leaking episode from 43% to 61%. Urodynamic results in these patients were consistent with the clinical results. Treatment with Oxybutynin chloride tablets was associated with an increase from baseline in maximum cystometric capacity from 230 mL to 279 mL, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 36 cm H2O to 33 cm H2O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H2O) from 39% to 20%.

As there is insufficient clinical data for pediatric populations under age 5, Oxybutynin chloride is not recommended for this age group.

Geriatric Use

Clinical studies of Oxybutynin chloride did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between healthy elderly and younger patients; however, a lower initial starting dose of 2.5 mg given 2 or 3 times a day has been recommended for the frail elderly due to a prolongation of the elimination half-life from 2 to 3 hours to 5 hours.2,3,4 In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Overactive bladder:

Oral:

Immediate release: 5 mg 2 to 3 times daily; maximum: 5 mg 4 times daily

Extended release: Initial: 5 to 10 mg once daily, adjust dose in 5 mg increments at weekly intervals; maximum: 30 mg once daily

Topical gel: Apply contents of 1 sachet (100 mg/g) or 1 actuation of the pump (100 mg/g) once daily.

Transdermal: Apply one 3.9 mg/day patch twice weekly (every 3 to 4 days)

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied); use with caution.

Oral:

>10%:

Central nervous system: Dizziness (5% to 17%), drowsiness (6% to 14%)

Gastrointestinal: Xerostomia (35% to 71%; dose related), constipation (9% to 15%), nausea (5% to 12%)

1% to 10%:

Cardiovascular: Cardiac arrhythmia (sinus; 1% to <5%), decreased blood pressure (1% to <5%), edema (1% to <5%), flushing (1% to <5%), hypertension (1% to <5%), palpitations (1% to <5%), peripheral edema (1% to <5%)

Central nervous system: Headache (8%), nervousness (7%), insomnia (3% to 6%), confusion (1% to <5%), falling (1% to 5%), fatigue (1% to <5%), flank pain (1% to <5%), pain (1% to <5%)

Dermatologic: Pruritus (1% to <5%), xeroderma (1% to <5%)

Endocrine & metabolic: Fluid retention (1% to <5%), hyperglycemia (1% to <5%), increased thirst (1% to <5%)

Gastrointestinal: Diarrhea (1% to 8%), dyspepsia (5% to 6%), abdominal pain (1% to <5%), dysphagia (1% to <5%), eructation (1% to <5%), flatulence (1% to <5%), unpleasant taste (1% to <5%), vomiting (1% to <5%), gastroesophageal reflux disease (≤1%)

Genitourinary: Urinary hesitancy (2% to 9%), urinary tract infection (7%), urinary retention (1% to 6%), cystitis (1% to <5%), dysuria (1% to <5%), pollakiuria (1% to <5%)

Infection: Fungal infection (1% to <5%)

Neuromuscular & skeletal: Arthralgia (1% to <5%), back pain (1% to <5%), limb pain (1% to <5%), weakness (1% to <5%)

Ophthalmic: Blurred vision (4% to 10%), eye irritation (1% to <5%), keratoconjunctivitis sicca (1% to <5%), xerophthalmia (3%)

Respiratory: Asthma (1% to <5%), bronchitis (1% to <5%), cough (1% to <5%), dry throat (1% to <5%), hoarseness (1% to <5%), nasal congestion (1% to <5%), dry nose (1% to <5%), nasopharyngitis (1% to <5%), pharyngolaryngeal pain (1% to <5%), sinus congestion (1% to <5%), upper respiratory tract infection (1% to <5%)

Topical gel:

>10%:

Gastrointestinal: Xerostomia (8% to 12%)

Local: Application site reaction (6% to 14%; includes anesthesia, irritation, pain, papules)

1% to 10%:

Central nervous system: Dizziness (3%), fatigue (2%), headache (2%)

Dermatologic: Pruritus (1%)

Gastrointestinal: Constipation (1%)

Genitourinary: Urinary tract infection (7%)

Local: Application site erythema (4%), application site rash (3%), application site pruritus (2% to 3%), application site dermatitis (2%)

Ophthalmic: Blurred vision (<2%), xerophthalmia (<2%)

Respiratory: Nasopharyngitis (3%)

Transdermal:

>10%: Local: Application site pruritus (14% to 17%)

1% to 10%:

Gastrointestinal: Xerostomia (4% to 10%), constipation (3%), diarrhea (3%)

Genitourinary: Dysuria (2%)

Local: Application site erythema (6% to 8%), application site vesicles (3%), application site rash (3%)

Ophthalmic: Visual disturbance (3%)

Postmarketing and/or case reports (Limited to important or life-threatening): Anaphylaxis, anorexia, cycloplegia, decreased gastrointestinal motility, glaucoma, hallucination, hypersensitivity reaction, impotence, suppressed lactation, memory impairment, mydriasis, psychotic reaction, prolonged Q-T interval on ECG, seizure, tachycardia

Incontinence episodes, postvoid residual (PVR), anticholinergic reactions.

Adverse events were not observed in animal reproduction studies.

This medication may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Oxybutynin can decrease perspiration and you may be more prone to heat stroke.

Commonly reported side effects of oxybutynin include: constipation, drowsiness, and local pruritus. Other side effects include: urinary tract infection, blurred vision, dizziness, dyspepsia, headache, nausea, rhinitis, and xerophthalmia. See below for a comprehensive list of adverse effects.

• Peak concentrations are reached within half to one hour. Effects of immediate release oxybutynin tablets are relatively short-lived but may last up to eight hours.
• Immediate-release oxybutynin is usually taken three to four times daily unless it is just used for night-time urinary incontinence when one dose is taken at night. An extended-release tablet (Ditropan XL) and a patch which is placed on the skin (Oxytrol) are also available.

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