Oxybutynin


Article Author:
Jennifer Dwyer


Article Editor:
Chad LaGrange


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Cynthia Oster


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Tehmina Warsi


Updated:
3/2/2019 6:11:55 PM

Indications

Oxybutynin is an anticholinergic medication that is 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 neurogenic bladder. It has been studied in and approved for patients over 5 years of age. These are FDA-approved indications.  

Occasionally, oxybutynin is used to treat bladder spasms provoked by indwelling ureteral stents or Foley catheters. However, this is not an FDA-approved use.[1][2][3][4]

Mechanism of Action

Oxybutynin is an anticholinergic medication that has antispasmodic activity against smooth muscle, including 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. This 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.[5][6][7][8]

Administration

Oxybutynin can be administered in a number of 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.

In adults, the typical starting dose is one, 5 mg tablet two to three times per day for the immediate release.  The patient should not exceed four, 5 mg tablets a day. In frail or elderly patients, a starting dose of 2.5 mg is reasonable. In pediatric patients over the age of five, the typical starting dose is one 5 mg tablet two to three times per day for the immediate release. The maximum dose is 5 mg, three times per day.

The syrup form is formulated as 1 mg/mL, so 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 recommended starting dose 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 a maximum of 30 mg daily. Pediatric patients age six and older should start at 5 mg, once daily, with a maximum dose of 20 mg daily. The extended-release form should not be given to patients under the age of six or in pediatric patients who cannot swallow the tablet whole as it should not be chewed, crushed, or divided.

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. It should be applied to 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.

Adverse Effects

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.[9][10]

The side effects associated with 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 discontinuation in 6.8% of patients.

Application site reactions for oxybutynin gel were reported in 5.4% of patients and for oxybutynin transdermal system in 16.8% of patients (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.

Contraindications

Oxybutynin is contraindicated in patients with urinary retention, poorly controlled narrow-angle glaucoma, and obstructive gastric disorders or gastric dysmotility. 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, patients with myasthenia gravis, and those with renal or hepatic impairments. 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 or may become pregnant.

There is also no evidence regarding the use of oxybutynin in nursing mothers.

Monitoring

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 also should be counseled that taking oxybutynin in a high-temperature environment may lead to heat prostration, which can manifest 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. Cytochrome P450 3A4 inhibitors (antimycotic agents like itraconazole or macrolide antibiotics like erythromycin) may alter oxybutynin pharmacokinetics and should be co-administered with caution.

Toxicity

Immediate care by a medical professional should be sought if an overdose is suspected. Symptoms of overdose 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 physician and nurse practitioner) who prescribe oxybutynin should be familiar with its adverse effect profile. The adverse effects are often dose-related. 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 also should be counseled that taking oxybutynin in a high-temperature environment may lead to heat prostration, which can manifest as fever and heat stroke due to decreased sweating


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Oxybutynin - Questions

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Which of the following medications can manage overactive bladder?



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Which of the following medications can be used in patients with detrusor instability?



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Which correctly describes oxybutynin?



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Which of the following is not an FDA approved indication for oxybutynin?



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What is the most commonly reported adverse effect of immediate release oral oxybutynin?



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Which of the following patients should not receive oxybutynin?



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Which of the following is not an appropriate dosing regimen?



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Which of the following is true regarding the safety profile of oxybutynin?



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Oxybutynin - References

References

Williams G,Hodson EM,Craig JC, Interventions for primary vesicoureteric reflux. The Cochrane database of systematic reviews. 2019 Feb 20;     [PubMed]
Löfling L,Sundström A,Kieler H,Bahmanyar S,Linder M, Exposure to antimuscarinic medications for treatment of overactive bladder and risk of lung cancer and colon cancer. Clinical epidemiology. 2019;     [PubMed]
Cetinel B,Onal B,Gultekin MH,Guzelsoy M,Turegun FA,Dincer M, Which antimuscarinic agents used in the treatment of overactive bladder increase heart rate? a prospective randomized clinical trial. International urology and nephrology. 2019 Feb 6;     [PubMed]
Thomas LH,Coupe J,Cross LD,Tan AL,Watkins CL, Interventions for treating urinary incontinence after stroke in adults. The Cochrane database of systematic reviews. 2019 Feb 1;     [PubMed]
Zur E, Topical Treatment of Primary Focal Hyperhidrosis, Part 1. International journal of pharmaceutical compounding. 2019 Jan-Feb;     [PubMed]
Hur M,Park SK,Yoon HK,Yoo S,Lee HC,Kim WH,Kim JT,Ku JH,Bahk JH, Comparative effectiveness of interventions for managing postoperative catheter-related bladder discomfort: a systematic review and network meta-analysis. Journal of anesthesia. 2019 Jan 2;     [PubMed]
Herbison P,McKenzie JE, Which anticholinergic is best for people with overactive bladders? A network meta-analysis. Neurourology and urodynamics. 2018 Dec 21;     [PubMed]
Tian Y,Wen Y,Sun J,Zhao L,Xiong Z,Qin F, Simultaneous quantification of oxybutynin and its active metabolite N-desethyl oxybutynin in rat plasma by ultra-high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study of oxybutynin transdermal patch. Biomedical chromatography : BMC. 2018 Dec 7;     [PubMed]
Vouri SM,Schootman M,Strope SA,Xian H,Olsen MA, Antimuscarinic use and discontinuation in an older adult population. Archives of gerontology and geriatrics. 2019 Jan - Feb;     [PubMed]
Vozmediano-Chicharro R,Madurga B,Blasco P, Efficacy of Transdermal Oxybutynin in the Treatment of Overactive Bladder Syndrome: Does It Make Sense Using It in 2017? Advances in urology. 2018;     [PubMed]

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