Oxybutynin Chloride

Pronunciation: (OX-i-BUE-ti-nin KLOR-ide)Class: Anticholinergic

Trade Names:Ditropan- Tablets 5 mg- Syrup 5 mg/5 mL

Trade Names:Ditropan XL- Tablets, ER 5 mg- Tablets, ER 10 mg- Tablets, ER 15 mg

Trade Names:Gelnique- Gel 10%

Trade Names:Oxytrol- Transdermal system, topical 36 mg of oxybutynin delivering 3.9 mg of oxybutynin/day.

Apo-Oxybutynin (Canada)Gen-Oxybutynin (Canada)Nu-Oxybutynin (Canada)PMS-Oxybutynin (Canada)Uromax (Canada)

Pharmacology

Increases bladder capacity, diminishes frequency of uninhibited contractions of detrusor muscle, and delays initial desire to void.

Pharmacokinetics

Absorption

ER

Following oral administration of the oxybutynin ER tablet, plasma levels rise for 4 to 6 h; thereafter, steady levels are maintained for up to 24 h. Steady-state levels are achieved by day 3 of repeated ER dosing.

Immediate-release tablet and syrup

Rapidly absorbed following oral administration, reaching the C _max within 1 h. Bioavailability is approximately 6%.

Topical gel

Transported across intact skin into the systemic circulation by passive diffusion across the stratum corneum. Steady-state concentrations are achieved within 7 days of continuous dosing.

Transdermal system

Following application of the first 3.9 mg/day system, plasma levels increase for approximately 24 to 48 h, reaching C _max of 3 to 4 ng/mL.

Distribution

Plasma concentrations of oxybutynin decline biexponentially following IV or oral administration.

Widely distributed to body tissues. The Vd was estimated to be 193 L after IV administration of oxybutynin chloride 5 mg.

Metabolism

Extensively metabolized by the liver, primarily by the CYP3A4 isozyme in the liver and gut wall. Transdermal administration bypasses the first-pass GI and hepatic metabolism.

Elimination

Less than 0.1% excreted unchanged in the urine.

Special Populations

Renal Function Impairment

No experience with use in patients with renal function impairment.

Hepatic Function Impairment

No experience with use in patients with hepatic function impairment.

Elderly

No differences in pharmacokinetics in elderly patients compared with younger patients.

Gender

No differences in pharmacokinetics based on gender.

Race

Available data suggest that there are no differences in the pharmacokinetics based on race in healthy volunteers. The effect of race on the pharmacokinetics of the topical gel has not been studied.

Showering Topical gel

Showering 1 h after application does not affect the overall systemic exposure to oxybutynin.

Sunscreen Topical gel

Concurrent application of sunscreen before or after application does not affect systemic exposure to oxybutynin.

Indications and Usage

Treatment of symptoms of bladder instability associated with voiding in patients with uninhibited and reflex neurogenic bladder (eg, urinary leakage, dysuria) (immediate-release tablet and syrup). Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency (ER tablet, topical gel, transdermal system); symptoms of detrusor over activity associated with neurological conditions (eg, spina bifida) in children 6 yr of age and older (ER tablet).

Unlabeled Uses

Hyperhidrosis.

Contraindications

Gastric retention; uncontrolled narrow-angle glaucoma; urinary retention; hypersensitivity to any component of the product.

ER tablet, immediate-release tablet, and syrup

Other severe decreased GI motility conditions.

Dosage and Administration

Immediate-release tablet or syrupAdults

PO 5 mg 2 to 3 times daily (max, 5 mg 4 times daily).

Children older than 5 yr of age

PO 5 mg twice daily (max, 5 mg 3 times daily).

Topical GelAdults

Topical gel Apply contents of 1 sachet once daily to dry, intact skin on the abdomen, upper arms/shoulder, or thighs.

ERAdults

PO 5 to 10 mg once daily adjusted in 5 mg increments at weekly intervals (max, 30 mg/day).

Children 6 yr of age and older

PO ER 5 mg once daily at approximately the same time. Adjust dose in 5 mg increments to achieve a balance of efficacy and tolerability (max, 20 mg/day).

Transdermal systemAdults

Transdermal 3.9 mg/day applied twice/wk (every 3 or 4 days) to dry, intact skin on abdomen, hip, or buttock, selecting a new application site with each system and avoiding using the same site within 7 days.

General Advice

• Transdermal system
• Remove patch from foil pouch, remove plastic strips covering adhesive layer, and immediately apply to dry, intact skin on the abdomen, buttock, or hip.
• Rotate application sites to avoid reapplication to same site within 7 days.
• To discard used patch, fold used patch, place in foil pouch from new patch, and discard in trash.

• Topical gel
• Rotate application site.
• Application should not be made to the same site on consecutive days.
• Apply immediately after the sachet is opened and contents expelled.
• Hands should be washed immediately after application.

Storage/Stability

Store at 59° to 86° F. Protect from moisture and humidity. Do not store patches outside foil pouch.

Drug Interactions

Anticholinergic drugs (eg, amantadine)

Increased risk of anticholinergic adverse reactions.

Beta-blockers (eg, atenolol)

Atenolol plasma levels may be elevated, increasing the risk of adverse reactions.

Digoxin

Increased plasma levels of slow-dissolution oral tablets may be increased.

Haloperidol

Worsening of schizophrenic symptoms; tardive dyskinesia; decreased serum haloperidol concentrations, reducing therapeutic effect.

Inhibitors of CYP3A4 (eg, azole antifungal agents [eg, itraconazole, ketoconazole], macrolide antibiotics [clarithromycin, erythromycin])

Oxybutynin plasma concentrations may be elevated. Coadminister with caution.

Phenothiazines (eg, chlorpromazine)

Decreased therapeutic effects of phenothiazines; increased incidence of anticholinergic adverse reactions.

Potassium chloride

Arrest or delay of potassium chloride tablet passage through the GI tract as a result of decreased GI motility.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

ER tablets

Hypertension, increased BP, palpitations (1% to less than 5%); arrhythmia, tachycardia (postmarketing).

Immediate-release tablets and syrup

Decreased and increased BP, palpitations, sinus arrhythmia (1% to 5%); tachycardia (postmarketing).

CNS

ER tablets

Somnolence (12%); headache (10%); asthenia (7%); dizziness (6%); confusional state, depression, dysgeusia, fatigue, insomnia, nervousness (1% to less than 5%); agitation, convulsions, hallucinations, psychotic disorder (postmarketing).

Immediate-release tablets and syrup

Dizziness (17%); somnolence (14%); headache (8%); nervousness (7%); insomnia (6%); asthenia, confusional state, dysgeusia, fatigue, sinus headache (1% to less than 5%); agitation, convulsions, hallucination, psychotic disorder (postmarketing).

Topical gel

Dizziness (3%); fatigue, headache (2%).

Transdermal system

Fatigue, headache, somnolence (more than 1%); dizziness (postmarketing).

Dermatologic

ER tablets

Dry skin, pruritus (1% to less than 5%); flushing, rash (postmarketing).

Immediate-release tablets and syrup

Dry skin, flushing, pruritus (1% to less than 5%); decreased sweating, rash (postmarketing).

Topical gel

Pruritus (1%).

Transdermal system

Flushing, rash (greater than 1%).

EENT

ER tablets

Blurred vision (8%); dry eyes, rhinitis (6%); dry throat, nasal dryness, nasopharyngitis, pharyngolaryngeal pain (1% to less than 5%).

Immediate-release tablets and syrup

Blurred vision (10%); dry throat, eye irritation, keratoconjunctivitis sicca, nasal congestion, nasal dryness, nasopharyngitis, pharyngolaryngeal pain (1% to less than 5%); cycloplegia, mydriasis (postmarketing).

Topical gel

Nasopharyngitis (3%).

Transdermal system

Abnormal vision (3%).

GI

ER tablets

Dry mouth (61%); constipation (13%); diarrhea, nausea (9%); dyspepsia (7%); abdominal pain, flatulence, gastroesophageal reflux disease, loose stools, vomiting (1% to less than 5%).

Immediate-release tablets and syrup

Dry mouth (71%); constipation (15%); nausea (12%); dyspepsia (6%); abdominal pain, decreased saliva secretion, diarrhea, dysphagia, eructation, flatulence, loose stools, tongue coating, upper abdominal pain, vomiting (1% to less than 5%); decrease GI motility (postmarketing).

Topical gel

Dry mouth (8%); viral gastroenteritis (2%); constipation (1%).

Transdermal system

Dry mouth (10%); constipation, diarrhea (3%); abdominal pain, flatulence, nausea (greater than 1%).

Genitourinary

ER tablets

Dysuria, UTI (5%); urinary hesitancy, urinary retention (1% to less than 5%); impotence (postmarketing).

Immediate-release tablets and syrup

Urinary hesitancy (9%); UTI (7%); urinary retention (6%); dysuria, pollakiuria (1% to less than 5%); impotence, suppression of lactation (postmarketing).

Topical gel

UTI (7%).

Transdermal system

Dysuria (2%).

Local

Topical gel

Application-site reactions including anesthesia, dermatitis, erythema, irritation, pain, papules, and pruritus (5%).

Transdermal system

Application-site pruritus (17%); application-site erythema (8%); application-site vesicles (4%); application-site macules, application-site rash (3%); application-site burning (greater than 1%).

Metabolic-Nutritional

Immediate-release tablets and syrup

Fluid retention, increased blood glucose, thirst (1% to less than 5%).

Musculoskeletal

ER tablets

Arthralgia, back pain, extremity pain (1% to less than 5%).

Immediate-release tablets and syrup

Arthralgia, back pain, extremity pain, flank pain (1% to less than 5%).

Transdermal system

Back pain (more than 1%).

Respiratory

ER tablets

Bronchitis, cough, sinusitis, upper respiratory tract infection (1% to less than 5%).

Immediate-release tablets and syrup

Asthma, bronchitis, cough, hoarseness, sinus congestion, UTI (1% to less than 5%).

Topical gel

Upper respiratory tract infection (5%).

Miscellaneous

ER tablets

Pain (7%); chest pain, cystitis, fall, peripheral edema (1% to less than 5%).

Immediate-release tablets and syrup

Cystitis, edema, fall, fungal infections, pain, peripheral edema (1% to less than 5%).

Precautions

Monitor Monitor patients for signs of anticholinergic CNS effects, especially during the first few months of therapy or after dose increases.

Pregnancy

Category B .

Lactation

Undetermined.

Children

Immediate release tablets and syrup

Safety and efficacy not established in children younger than 5 yr of age.

ER

Safety and efficacy not established in children younger than 6 yr of age.

Topical gel, transdermal system

Safety and efficacy not established.

Hypersensitivity

Patients developing skin hypersensitivity to oxybutynin topical gel should discontinue treatment.

Special Risk Patients

Use with caution in elderly patients and in patients with renal or hepatic function impairment or autonomic neuropathy. Use with caution in elderly patients, and in patients with hepatic or renal function impairment, GI obstruction, bladder outflow obstruction, ulcerative colitis, intestinal atony, and myasthenia gravis, and in patients with preexisting dementia who are receiving cholinesterase inhibitors.

Anticholinergic effects

Use cautiously with phenothiazines or other drugs with anticholinergic properties because adverse reactions will be additive.

Cardiac and other effects

May aggravate symptoms of hyperthyroidism, coronary heart disease, CHF, cardiac arrhythmias, tachycardia, hypertension, hiatal hernia, and prostatic hypertrophy.

CNS effects

CNS anticholinergic effects (eg, agitation, confusion, hallucination, somnolence) can occur.

Diarrhea

Diarrhea may be an early symptom of intestinal obstruction in which oxybutynin is contraindicated.

Flammable gel

The topical gel is alcohol-based and flammable. Patients should avoid open fire or smoking until gel is dry.

GI disorders

Administration to patients with ulcerative colitis may suppress GI motility and produce paralytic ileus, precipitating or aggravating toxic megacolon. Use with caution.

Heat prostration

Heat prostration may occur when exposed to high environmental temperature.

Skin transference

Transfer of oxybutynin topical gel to another person can occur when vigorous skin-to-skin contact is made with the application site.

Urinary retention

Because risk may be increased, use with caution.

Overdosage

Symptoms

Agitation, cardiac arrhythmia, CNS excitation, coma, dehydration, dilated pupils, disorientation, dry skin, flushing, fever, memory loss, nausea, tachycardia, respiratory depression, stupor, urinary retention, vomiting.

Patient Information

• Instruct patient to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Teach patient to use bladder massage to empty bladder.
• Advise patient to use caution in hot weather to reduce risk of heat stroke.
• Advise patient that drug may cause drowsiness or dizziness, and to use caution while driving or performing other tasks requiring mental alertness.
• Advise patient to take oxybutynin ER tablet whole with liquids and not to chew, divide, or crush.
• Inform patient not to be concerned if noticing a tablet in the stool; the tablet shell is eliminated from the body but the drug is released from the tablet at a controlled rate.

• Transdermal system
• Advise patient to review the patient information leaflet that comes with each prescription before using the first time and with each refill.
• Ensure that patient understands how to store, apply, and discard patches.
• Advise patient that new patch is applied twice/wk (eg, every 3 to 4 days) and to rotate application sites to avoid reapplication to the same site within 7 days.
• Advise patient that if patch comes off before scheduled replacement, to discard and apply new patch to new application site and establish new reapplication schedule.
• Advise patient to notify health care provider if application-site reactions occur and are bothersome or occur with each application.

• Topical gel
• Advise patients that this product is alcohol-based and to avoid open fire or smoking until gel has dried.
• Advise patients not to apply gel to areas of the skin that have been treated with oils, lotions, or powder because the absorption of the product through the skin may be affected. However, the product may be used with sunscreen.
• Advise patients to contact their health care provider if continued itching, rash, or redness occurs.
• Advise patients that the approved application sites for the product are abdomen, upper arms/shoulder, and thigh.
• Advise patients to avoid contact with eyes, nose, open sores, recently shaved skin, and skin with rashes or other areas not approved for application of the product.
• Inform patients that it is recommended that the approved application site be changed with each dose.
• Instruct patients to wash the application site and their hands with soap and water before applying product.
• Instruct patients to avoid bathing, swimming, showering, exercising or immersing the application site in water for 1 h after application.
• Instruct patients that the application site may be covered with clothing once the gel has dried.
• Advise patients that if the gel gets in their eyes, to rinse their eyes immediately with warm, clean water to flush out any gel and to seek medical attention if needed.

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