|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Special Alerts
Transdermal Patches: Risk of Burns During MRI - March 2009
The U.S. Food and Drug Administration (FDA) has issued a public health advisory regarding the risk of burns associated with the use of transdermal medication patches containing aluminum or other metals during MRI screening. The package labeling for certain metal-containing patches includes a warning related to the risk of burns if the patches are not removed prior to MRI procedures. However, not all transdermal medication patches with metallic backings have this warning in the labeling. Although metal materials are present in certain patches, it may not be visible. The FDA is currently reviewing the components of all transdermal medication systems to ensure that proper warnings are present in the labeling of those patches that do contain metal materials. In the interim, the FDA recommends that healthcare professionals who refer patients to have an MRI procedure should identify patients who are wearing a transdermal medication patch prior to the scan. Those patients who are wearing a transdermal medication patch should be advised on the proper removal of the patch prior to the procedure as well as reapplication following the scan.
Additional information can be found at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm111493.htm
Medication Safety Issues
Sound-alike/look-alike issues:
Oxybutynin may be confused with OxyContin®
Ditropan® may be confused with Detrol®, diazepam, Diprivan®, dithranol
Transdermal patch may contain conducting metal (eg, aluminum); remove patch prior to MRI.
Pronunciation
(oks i BYOO ti nin)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes gel, transdermal patch
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Antispasmodic for neurogenic bladder (urgency, frequency, leakage, urge incontinence, dysuria); extended release formulation also indicated for treatment of symptoms associated with detrusor overactivity due to a neurological condition (eg, spina bifida)
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. There are no adequate and well-controlled studies in pregnant women; use during pregnancy only if clearly needed.
Lactation
Excretion in breast milk unknown/use caution
Breast-Feeding Considerations
Suppression of lactation has been reported.
Contraindications
Hypersensitivity to oxybutynin or any component of the formulation; patients with or at risk for uncontrolled narrow-angle glaucoma, urinary retention, gastric retention or conditions with severely decreased GI motility
Warnings/Precautions
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (eg, agitation, confusion, hallucinations, somnolence) which may require dose reduction or discontinuation of therapy.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Heat prostration: May increase the risk of heat prostration.
Disease-related concerns:
• Autonomic neuropathy: Use with caution in patients with autonomic neuropathy; may exacerbate condition.
• Cardiovascular disease: Use with caution in patients with CAD, heart failure, hypertension, and/or cardiac arrhythmias; may exacerbate condition.
• Dementia: Use with caution in patients with dementia treated with cholinesterase inhibitors; may aggravate symptoms of disease.
• Gastrointestinal disorders: Use with caution in patients with ulcerative colitis, intestinal atony, gastroesophageal reflux or with medications that may exacerbate esophagitis (eg, bisphosphonates). May decrease GI motility; in patients with ulcerative colitis, use may increase risk of paralytic ileus or toxic megacolon.
• Glaucoma: Use with caution in patients with treated angle-closure glaucoma; may exacerbate condition; use is contraindicated with uncontrolled narrow-angle glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment; due to limited experience.
• Hiatal hernia: Use with caution in patients with hiatal hernia.
• Hyperthyroidism: Use with caution in patients with hyperthyroidism; may exacerbate condition.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; may exacerbate condition.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture; may cause urinary retention.
• Renal impairment: Use with caution in patients with renal impairment; due to limited experience. Use caution with bladder outflow obstruction; may increase risk of urinary retention.
Special populations:
• Elderly: Use with caution in the elderly due to anticholinergic activity (eg, confusion, constipation, blurred vision, and tachycardia).
Dosage form specific issues:
• Extended release formulation: The extended release formulation consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction (rare).
• Topical gel: To minimize transferring medication to others, cover treatment area with clothing after gel has dried. Discontinue use if skin irritation occurs. Contains ethanol; do not expose to open flame or smoking until gel has dried.
• Transdermal patch: May contain conducting metal (eg, aluminum); remove patch prior to MRI.
Adverse Reactions
Oral:
>10%:
Central nervous system: Dizziness (4% to 17%), somnolence (2% to 14%)
Gastrointestinal: Xerostomia (29% to 71%; dose related), constipation (7% to 15%), nausea (2% to 12%)
5% to 10%:
Central nervous system: Headache (6% to 10%), pain (1% to 7%), nervousness (1% to 7%), insomnia (1% to 6%)
Gastrointestinal: Diarrhea (1% to 9%), dyspepsia (5% to 7%)
Genitourinary: Urinary hesitation (9%), urinary tract infection (5% to 7%), urinary retention (6%)
Neuromuscular & skeletal: Weakness (3% to 7%)
Ocular: Blurred vision (1% to 10%), dry eyes (3% to 6%)
Respiratory: Rhinitis (2% to 6%)
1% to <5%: Abdominal pain, aptyalism, arrhythmia, arthralgia, asthma, back pain, bronchitis, chest pain, confusion, cough, cystitis, depression, dry skin, dry throat, dysgeusia, dysphagia, dysuria, edema, eructation, extremity pain, eye irritation, fatigue, flank pain, flatulence, fluid retention, flushing, fungal infection, gastrointestinal reflux disease, hoarseness, hyperglycemia, hyper-/hypotension, keratoconjunctivitis sicca, loose stools, nasal congestion, nasal dryness, nasopharyngitis, palpitation, peripheral edema, pharyngolaryngeal pain, pollakiuria, pruritus, seizure, sinus congestion, sinus headache, sinusitis, thirst, tongue coated, upper respiratory tract infection, vomiting
Postmarketing and/or case reports: Agitation, cycloplegia, GI motility decreased, hallucination, impotence, lactation suppression, memory impairment, mydriasis, psychotic disorder, QTc prolongation, rash, sweating decreased, tachycardia
Topical gel:
1% to 10%:
Central nervous system: Dizziness (2% to 3%), fatigue (2%), headache (2%)
Dermatologic: Pruritus (1%)
Gastrointestinal: Xerostomia (7% to 8%), gastroenteritis (2%), constipation (1%)
Genitourinary: Urinary tract infection (7%)
Local: Application site reaction (5%; includes anesthesia, dermatitis, erythema, irritation, pain, papules, pruritus)
Respiratory: Nasopharyngitis (3%)
Transdermal:
>10%: Local: Application site reaction (17%), pruritus (14%)
1% to 10%:
Gastrointestinal: Xerostomia (4% to 10%), diarrhea (3%), constipation (3%)
Genitourinary: Dysuria (2%)
Local: Erythema (6% to 8%), vesicles (3%), rash (3%)
Ocular: Vision changes (3%)
Postmarketing and/or case reports: Cardiac arrhythmia, cycloplegia, hallucinations, lactation suppressed, myocarditis, impotence, seizure, sweating decreased, tachycardia
Metabolism/Transport Effects
Substrate of CYP3A4 (minor); Inhibits CYP2C8 (weak), 2D6 (weak), 3A4 (weak)
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Cannabinoids: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoids. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Risk D: Consider therapy modification
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Secretin: Anticholinergic Agents may diminish the stimulatory effect of Secretin. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Ethanol: Use ethanol with caution (may increase CNS depression and toxicity). Watch for sedation.
Storage
Immediate release: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Protect syrup from light.
Extended release: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and humidity.
Gel sachet, transdermal patch: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture and humidity. Keel gel away from open flame. Keep patch in sealed pouch. Throw away used sachets or patches where children and pets cannot reach.
Mechanism of Action
Direct antispasmodic effect on smooth muscle, also inhibits the action of acetylcholine on smooth muscle (exhibits 1/5 the anticholinergic activity of atropine, but is 4-10 times the antispasmodic activity); does not block effects at skeletal muscle or at autonomic ganglia; increases bladder capacity, decreases uninhibited contractions, and delays desire to void, therefore, decreases urgency and frequency
Pharmacodynamics/Kinetics
Onset of action: Oral: 30-60 minutes
Peak effect: 3-6 hours
Duration: 6-10 hours (up to 24 hours for extended release oral formulation)
Absorption: Oral: Rapid and well absorbed; Transdermal: High
Distribution: I.V.: Vd: 193 L
Metabolism: Hepatic via CYP3A4; Oral: High first-pass metabolism; forms active and inactive metabolites
Bioavailability: Oral: ~6%
Half-life elimination: I.V.: ~2 hours (parent drug), 7-8 hours (metabolites); Oral: ~2-3 hours
Time to peak, serum: Oral: Immediate release: ~60 minutes; Extended release: 4-6 hours; Transdermal: 24-48 hours
Excretion: Urine, as metabolites and unchanged drug (<0.1%)
Dosage
Oral:
Children:
1-5 years (unlabeled use): 0.2 mg/kg/dose 2-4 times/day
>5 years: 5 mg twice daily, up to 5 mg 3 times/day maximum
>6 years: Extended release: 5 mg once daily; adjust dose in 5 mg increments; maximum dose: 20 mg/day
Adults: 5 mg 2-3 times/day up to 5 mg 4 times/day maximum
Extended release: Initial: 5-10 mg once daily, adjust dose in 5 mg increments at weekly intervals; maximum: 30 mg daily
Elderly: Regular release: Initial dose: 2.5 mg 2-3 times/day; increase as needed to 5 mg 2-3 times/day
Topical gel: Adults: Apply contents of 1 sachet (100 mg/g) once daily
Transdermal: Adults: Apply one 3.9 mg/day patch twice weekly (every 3-4 days)
Note: Should be discontinued periodically to determine whether the patient can manage without the drug and to minimize resistance to the drug
Administration: Oral
Immediate release tablets and solution should be administered on an empty stomach with water. Extended release tablets may be taken with or without food and must be swallowed whole with liquid; do not crush, divide, or chew; take at approximately the same time each day.
Administration: Topical
Topical gel: For topical use only. Apply to clean, dry, intact skin on abdomen, thighs, or upper arms/shoulders. Rotate site; do not apply to same site on consecutive days. Wash hands after use. Cover treated area with clothing after gel has dried to prevent transfer of medication to others. Do not bathe, shower, or swim until 1 hour after gel applied.
Administration: Other
Transdermal: Apply to clean, dry skin on abdomen, hip, or buttock. Select a new site for each new system (avoid reapplication to same site within 7 days).
Monitoring Parameters
Incontinence episodes, postvoid residual (PVR)
Test Interactions
May suppress the wheal and flare reactions to skin test antigens.
Dietary Considerations
Food causes a slight delay in the absorption of the oral solution and bioavailability is increased by ~25%. Absorption of the extended release tablet is not affected by food.
Patient Education
Take prescribed oral dose preferably on an empty stomach, 1 hour before or 2 hours after meals. Swallow extended-release tablets whole; do not chew or crush. You may experience dizziness, lightheadedness, or drowsiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth or changes in appetite (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help); constipation (increased exercise, fluids, fruit, fiber, or stool softener may help); decreased sexual ability (reversible with discontinuance of drug); or decreased sweating (use caution in hot weather, avoid extreme exercise or activity). Use alcohol with caution; may increase drowsiness. Report rapid heartbeat, palpitations, or chest pain; difficulty voiding; or vision changes. Breast-feeding precaution: Consult prescriber if breast-feeding.
Geriatric Considerations
Caution should be used in the elderly due to anticholinergic activity (eg, confusion, constipation, blurred vision, and tachycardia). Start with lower doses. Transdermal dosage form may have less potential for these effects. Oxybutynin may cause memory problems in the elderly. A study of 12 healthy volunteers with an average age of 69 showed cognitive decline while taking the drug (J Am Geriatr Soc, 1998, L46:8-13). Studies using transdermal dosage form did not reveal any differences in safety or efficacy between elderly and younger adults.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia and changes in salivation (normal salivary flow resumes upon discontinuation), and taste perversion.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Drowsiness is common; may cause insomnia or dizziness
Mental Health: Effects on Psychiatric Treatment
Concurrent use with psychotropics may produce additive sedation and anticholinergic side effects (dry mouth)
Nursing: Physical Assessment/Monitoring
Assess other prescriptions, OTC medications, or herbal products patient may be taking for interactions. Assess voiding pattern, incontinent episodes, frequency, urgency, distention, and urinary retention prior to beginning therapy and periodically with long-term use. Assess knowledge/teach patient appropriate use, possible side effects, and symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gel, topical, as chloride:
Gelnique™: 10% (1 g) [contains ethanol]
Syrup, as chloride: 5 mg/5 mL (473 mL)
Tablet, as chloride: 5 mg
Ditropan®: 5 mg
Tablet, extended release, as chloride: 5 mg, 10 mg, 15 mg
Ditropan XL®: 5 mg, 10 mg, 15 mg
Transdermal system:
Oxytrol®: 3.9 mg/day (8s) [39 cm2; total oxybutynin 36 mg]
Pricing: U.S. (www.drugstore.com)
Gel (Gelnique)
10% (30): $129.98
Patch, twice-weekly (Oxytrol)
3.9 mg/24 hrs (8): $148.83
Syrup (Oxybutynin Chloride)
5 mg/5 mL (120): $24.99
Tablet, 24-hour (Ditropan XL)
5 mg (30): $117.73
10 mg (30): $115.37
15 mg (30): $121.52
Tablet, 24-hour (Oxybutynin Chloride)
5 mg (100): $289.98
10 mg (100): $292.00
15 mg (100): $299.99
Tablets (Ditropan)
5 mg (60): $62.99
Tablets (Oxybutynin Chloride)
5 mg (60): $13.99
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
|
