Continuing Education Activity
Oxybutynin is an anticholinergic medication that is FDA-approved and indicated in patients with overactive bladder or symptoms of detrusor overactivity, including urinary frequency and urgency. It has been studied and approved for patients over five years of age. It also is indicated in patients with detrusor instability related to neurogenic bladder. Occasionally, oxybutynin indications include treating bladder spasms provoked by indwelling ureteral stents or Foley catheters. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of oxybutynin so providers can direct patient therapy to optimal outcomes where anticholinergic therapy is indicated in patients with overactive bladder.
- Describe the mechanism of action of oxybutynin.
- Identify the approved and off-label indications for using oxybutynin.
- Summarize the adverse event profile and contraindications of oxybutynin.
- Review the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from anticholinergic therapy with oxybutynin.
Oxybutynin is an anticholinergic medication indicated in patients with overactive bladder or symptoms of detrusor overactivity, including urinary frequency and urgency. Animal studies have shown that it has four to ten times the antispasmodic effect of atropine. It also is indicated in patients with detrusor instability related to the neurogenic bladder (e.g., spina bifida). It has been studied and approved for patients over five years of age.
Occasionally, oxybutynin is used to treat bladder spasms provoked by indwelling ureteral stents or Foley catheters. However, this is not an FDA-approved use. It is also used in primary focal hyperhidrosis.
Mechanism of Action
Oxybutynin is an anticholinergic medication with antispasmodic activity against smooth muscle, including the bladder smooth muscle. The active metabolite is N-desethyloxybutynin. It blocks the muscarinic effect of acetylcholine by competitively inhibiting the postganglionic muscarinic 1, 2, and 3 receptors. It causes bladder smooth muscle relaxation, which results in increased bladder capacity and decreased urinary urgency and frequency. It also has been shown to delay the initial desire to void.
Oxybutynin acts by competitive acetylcholine antagonism at postganglionic muscarinic receptors, resulting in the relaxation of bladder smooth muscle. Several dosage forms are approved by the FDA: immediate oral release, oral extended-release, topical gel, and transdermal patch. Oxybutynin is developed for intravesical instillation, and as a rectal suppository, a vaginal preparation is currently under development. Each formulation has different efficacy and adverse-event profiles.
Absorption: Oxybutynin is quickly absorbed following oral administration of oxybutynin chloride immediate-release tablets and has an absolute bioavailability of about 6% (ranges between 1.6 to 10.9%). It achieves Cmax within one hour and has approximately 2 to 3 hours of plasma half-life. The for the tablets.
Food Effects: When co-administered with food, clinical data in the literature shows that oxybutynin solution has a slightly delayed absorption and increased bioavailability by 25%.
Distribution: Oxybutynin has a large volume of distribution (193 L) following intravenous 5 mg oxybutynin chloride administration. In addition, both enantiomers of oxybutynin (R and S) are highly protein-bound (99%).
Metabolism: In the liver, oxybutynin gets metabolized by the cytochrome P450 enzyme systems (mostly via CYP3A4). As a result of metabolism, two metabolites are formed, metabolite phenyl cyclohexyl glycolic acid is inactive, and desethyl oxybutynin is pharmacologically active.
Excretion: Oxybutynin is mainly metabolized in the liver, and less than 0.1% of the administered dose gets excreted unchanged in the urine and less than 0.1% as desethyloxybutynin metabolite.
Oxybutynin can be administered in several ways. The most common is pill or tablet form, which comes as immediate release or long-acting. The dosage starts at 5 mg for both the immediate and long-acting forms. It also can be administered as a syrup, transdermal patch, or gel. The syrup form is formulated as 1 mg/mL, and the same starting and maximum doses are used as the immediate-release tablet. It is distributed in 16-ounce bottles. The long-acting or extended-release tablets contain 5 mg, 10 mg, or 15 mg of oxybutynin chloride. It is intended to be taken as a once-a-day oral medication and uses an osmotic pressure delivery system to release the medication over 24 hours. The oral forms of oxybutynin are absorbed similarly whether the patient is in the fed or fasted state.
The oxybutynin transdermal system or patch delivers the medication continuously over three to four days after application. It contains 36 mg of oxybutynin, making the average daily absorbed dose 3.9 mg. Steady-state concentrations occur during the second application. The patch should be applied to the abdomen, buttock, or hip. Safety in pediatric patients has not been established.
Oxybutynin gel (10%) comes in sachets, and the contents of one sachet should be applied to clean, dry, intact skin on the abdomen, upper arms, or thighs. Steady-state concentrations occur within seven days of continuous dosing. Application sites should be rotated. Safety in pediatric patients has not been established.
Over Active Bladder
- In adults, the typical starting dose is one 5 mg tablet two to three times per day for immediate release. The patient should not exceed four 5 mg tablets a day.
- The recommended starting dose for long-acting or extended-release in adults is 5 mg, once daily, and it should be taken at the same time each day. The dose may be increased by 5 mg, up to 30 mg daily.
- Apply the content of one actuation of the pump or one sachet daily for topical gel formulation.
- Apply one 3.9 mg transdermal patch twice weekly, remove the old patch, and apply the new patch on the same two days of each week. As an OTC product, females are to apply one 3.9 mg patch every fourth day.
- In frail or elderly patients, a starting dose of 2.5 mg two to three times per day is proper dosing for immediate release due to prolonging elimination half-life from 2 to 3 hours to 5 hours.
- The typical starting dose in pediatric patients over five is one 5 mg tablet two to three times per day for immediate release. The maximum dose is 5 mg, three times per day.
- Pediatric patients aged six and older should start at 5 mg long-acting or extended-release, once daily, with a maximum of 20 mg daily.
- The extended-release form should not be given to patients under six or pediatric patients who cannot swallow the tablet whole, as it should not be chewed, crushed, or divided.
- Oxybutynin is category B for pregnant patients. Animal studies have not shown definitive evidence of harm to the fetus, but safety has not been established for women who are pregnant or may become pregnant. There is also no evidence regarding the use of oxybutynin in nursing mothers. When used chronically in breastfeeding women, monitor the infant for possible signs of decreased milk production (e.g., in-satiety, poor weight gain).
Primary Focal Hyperhidrosis
- Oxybutynin IR 2.5 mg is administered once daily and gradually titrated as tolerated between 5 to 10 mg daily in two divided doses.
- Extended-release oxybutynin dose is 5 to 10 mg once daily.
Adverse effects for immediate release oxybutynin include dry mouth (71.4%), dizziness (16.6%), constipation (15.1%), somnolence (14.0%), and nausea (11.6%). Less common side effects include blurred vision (9.6%), urinary hesitation (8.5%), urinary retention (6.0%), and dyspepsia (6.0%). Of note, dry mouth was a dose-related side effect. Oxybutynin hydrochloride has a favorable profile compared to other antimuscarinic drugs concerning increased heart rate adverse effects.
The side effects of extended-release oxybutynin are similar, but rates have been reported as lower than the immediate-release form. These include dry mouth (29% to 61%), constipation (7% to 13%). somnolence (2% to 12%), headache (6% to 10%), diarrhea (7% to 9%), nausea (2% to 9%), blurred vision (1% to 8%), dry eyes (3% to 6%). Again, dry mouth was a dose-related side effect. Adverse events led to the discontinuation of medicine in 6.8% of patients.
Application site reactions were reported in 5.4% of patients for oxybutynin gel and 16.8% for oxybutynin transdermal system (versus 6.1% of patients in the placebo group). Dry mouth was much less common in patients receiving transdermal oxybutynin than the oral forms, reported as 7.5% for the gel and 9.6% for the patch. Adverse effects are often dose-related.
Oxybutynin is contraindicated in patients with urinary retention, bladder obstruction, poorly controlled narrow-angle glaucoma, obstructive gastric disorders, or gastric dysmotility. In addition, it should not be used in patients who have hypersensitivity to the drug or its components.
Cautious use is recommended for elderly or frail patients, those with dementia treated with cholinesterase inhibitors, Parkinson disease, patients with myasthenia gravis, and those with renal or hepatic impairments.
The dose of the extended-release formulation needs to be reduced or stopped if the patient experiences the anticholinergic central nervous system adverse reactions to oxybutynin. Also exercise caution in patients with autonomic neuropathy, with the use of extended-release formulation, as it may aggravate the symptoms of decreased gastric mobility.
Patients should be monitored for anticholinergic side effects related to the central nervous system, including hallucinations, agitation, confusion, and somnolence. This is particularly important in elderly patients and within the first few months of treatment or after increasing the dose of oxybutynin.
Patients should be counseled that increased drowsiness may occur with concomitant alcohol use. Patients should also be counseled that taking oxybutynin in a high-temperature environment may lead to heat prostration, manifesting as fever and heat stroke due to decreased sweating.
Using oxybutynin with other anticholinergic medications can increase the frequency and severity of the above-mentioned adverse effects. In addition, Cytochrome P 450 3A4 inhibitors (antimycotic agents like itraconazole or macrolide antibiotics like erythromycin) may alter oxybutynin pharmacokinetics and should be co-administered with caution.
Immediate care by a medical professional should be sought if an overdose is suspected. Overdose symptoms include central nervous system overactivity, fever, cardiac arrhythmias, vomiting, respiratory failure, paralysis, and coma. Treatment includes supportive care. Activated charcoal may be administered as well as a cathartic agent. Two overdoses of 100 mg ingestions were reported, one in a 13-year-old boy and another in a 34-year-old woman. There was a report of simultaneous alcohol ingestions. Both patients received supportive care, which resulted in complete recovery.
Enhancing Healthcare Team Outcomes
Healthcare workers (including the primary care physicians, physician assistants, and nurse practitioners) who prescribe oxybutynin should be familiar with its adverse effect profile. The adverse reactions of oxybutynin are often dose-related. Patients should be monitored for anticholinergic side effects related to the central nervous system, including hallucinations, agitation, confusion, and somnolence. These adverse reactions are particularly important in elderly patients and within the first few months of treatment or after increasing the dose of oxybutynin.
Pharmacists should perform medication reconciliation and counsel patients on an increased risk of drowsiness with concomitant alcohol use. Patients should also be counseled that taking oxybutynin in a high-temperature environment may lead to heat prostration, manifesting as fever and heat stroke due to decreased sweating. Nursing should verify the patient understanding of medicine and check the dose before administration to the patient. Open communication among interprofessional team members can improve efficacy and safety outcomes for patients treated with oxybutynin. [Level 5]