Oxybutynin - Drug Monograph

Introduction

Oxybutynin is an anticholinergic medication primarily used to manage overactive bladder (OAB) symptoms. As a muscarinic receptor antagonist, it represents a cornerstone therapy for urinary incontinence, urgency, and frequency. First approved by the FDA in 1975, oxybutynin remains one of the most prescribed medications for bladder dysfunction, available in multiple formulations including immediate-release tablets, extended-release tablets, transdermal patches, and topical gel.

Mechanism of Action

Oxybutynin exerts its therapeutic effects through competitive inhibition of muscarinic acetylcholine receptors, particularly the M1 and M3 subtypes. In the detrusor muscle of the bladder, antagonism of M3 receptors prevents acetylcholine-induced contraction, resulting in:

• Reduced bladder muscle spasms
• Increased bladder capacity
• Decreased urinary frequency and urgency
• Diminished involuntary bladder contractions

The drug also exhibits local anesthetic properties and direct antispasmodic effects on smooth muscle, though these contribute minimally to its clinical efficacy in OAB management.

Indications

• Overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency
• Neurogenic bladder dysfunction (e.g., in patients with spinal cord injuries or multiple sclerosis)

• Nocturnal enuresis in children (typically ≥6 years old)
• Hyperhidrosis (excessive sweating)
• Pediatric neurogenic bladder

Dosage and Administration

• Immediate-release tablets: 5 mg 2-3 times daily (max 5 mg 4 times daily)
• Extended-release tablets: 5-10 mg once daily (max 30 mg daily)
• Transdermal patch: Apply one patch twice weekly (every 3-4 days)
• Topical gel: 1 sachet (100 mg/g, 1 g oxybutynin) applied once daily

Initiate with lower doses due to increased sensitivity to anticholinergic effects

• Immediate-release: 5 mg twice daily (max 5 mg 3 times daily)
• Extended-release: 5 mg once daily (max 20 mg daily)

No specific dosage adjustment required

Use with caution; consider dose reduction

Pharmacokinetics

Well absorbed orally but undergoes extensive first-pass metabolism (bioavailability ~6% for immediate-release) Extended-release formulations provide more consistent plasma concentrations Transdermal administration bypasses first-pass metabolism

Volume of distribution: ~193 L Protein binding: Approximately 90% Crosses blood-brain barrier and placenta

Extensively metabolized hepatically via CYP3A4 to active metabolite N-desethyloxybutynin

Half-life: 2-3 hours (immediate-release); 12-13 hours (extended-release) Primarily excreted renally (≤0.1% unchanged) Dialyzability: Unlikely due to extensive protein binding

Contraindications

• Known hypersensitivity to oxybutynin or any component of the formulation
• Urinary retention
• Gastric retention
• Uncontrolled narrow-angle glaucoma
• Myasthenia gravis
• Obstructive gastrointestinal conditions (e.g., paralytic ileus, intestinal atony)
• Severe ulcerative colitis or toxic megacolon

Warnings and Precautions

May cause drowsiness, dizziness, or blurred vision; caution patients about driving or operating machinery

Reduced sweating can lead to heat stroke in hot environments

Increased risk of cognitive impairment, delirium, and falls

Category B - Use only if clearly needed

Monitor for paradoxical agitation and central nervous system effects

Metabolism may be impaired; monitor for increased adverse effects

May mask symptoms of UTI; evaluate for infection if symptoms worsen

Drug Interactions

Ketoconazole, itraconazole, clarithromycin - may increase oxybutynin concentrations

Increased anticholinergic adverse effects (e.g., with tricyclic antidepressants, antihistamines)

May antagonize gastrointestinal effects

May enhance sedative effects

Adverse Effects

• Dry mouth (61%)
• Constipation (13%)
• Somnolence (12%)
• blurred vision (8%)
• Dizziness (6%)

• Nausea
• Fatigue
• Headache
• Urinary retention
• Abdominal pain
• Diarrhea

• Angioedema
• Anaphylactic reactions
• QT prolongation
• Cognitive impairment
• Delirium
• Hyperthermia
• Glaucoma exacerbation

Monitoring Parameters

• Symptom improvement (voiding diary parameters)
• Adverse effects (particularly anticholinergic effects)
• Cognitive function in elderly patients
• Intraocular pressure in patients with glaucoma risk factors
• Residual urine volume in patients with voiding dysfunction
• Hepatic function in patients with liver disease
• Signs of urinary retention

Patient Education

• Take with food to reduce gastrointestinal upset
• Immediate-release tablets may cause more dry mouth than extended-release formulations
• Transdermal patch: Apply to dry, intact skin on abdomen, hip, or buttock; rotate application sites
• Topical gel: Apply to clean, dry, intact skin on abdomen, upper arms, or thighs; allow to dry before dressing
• Report immediately: Difficulty urinating, eye pain, skin rash, or swelling
• Use sugar-free candy or gum for dry mouth relief
• Maintain adequate fluid intake to prevent constipation
• Avoid excessive heat exposure due to reduced sweating capacity
• Do not abruptly discontinue without medical supervision
• Inform all healthcare providers about oxybutynin use

References

1. Drugs.com. Oxybutynin Professional Monograph. 2023 2. Micromedex Solutions. Oxybutynin Drug Information. IBM Watson Health 3. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Oxybutynin 4. Gormley EA, et al. Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline. J Urol. 2019 5. Novara G, et al. Systematic Review and Meta-analysis of Anticholinergic Drugs for Overactive Bladder. Eur Urol. 2008 6. FDA Prescribing Information: Ditropan, Oxytrol, Gelnique 7. Abrams P, et al. Review of Overactive Bladder and Antimuscarinics. Neurourol Urodyn. 2010