Oxybutynin

Overview

Oxybutynin (Ditropan®, Oxytrol®) is a genitourinary smooth muscle relaxant that may be useful in dogs and cats for the management of urinary bladder disorders associated with detrusor muscle instability or hyperreflexia.

Oxybutynin is considered a urinary antispasmodic and exerts both antimuscarinic (atropine-like) and spasmolytic (papaverine-like) effects. Its smooth muscle–relaxing activity is most pronounced in the detrusor muscle of the urinary bladder and in the small and large intestine, and it has no appreciable effect on vascular smooth muscle, skeletal muscle or autonomic ganglia.

Mechanism of Action (MOA): Oxybutynin produces direct antimuscarinic and spasmolytic effects on smooth muscle. It increases bladder capacity, reduces uninhibited detrusor contractions, and delays the urge to void; these effects were characterized in people with neurogenic bladders, and the drug’s effect on detrusor relaxation in dogs is not well reported.

Indications

Oxybutynin may be used as adjunctive therapy for urinary bladder disorders associated with detrusor muscle instability or hyperreflexia in dogs and cats.

• Detrusor hyperreflexia (dogs): Adjunctive treatment of refractory urinary incontinence associated with detrusor hyperreflexia, also described as overactive bladder.
• Detrusor instability (cats): Adjunctive therapy for FeLV-associated detrusor instability.
• Urge incontinence: Oxybutynin may be considered as symptomatic therapy in patients with urge incontinence, severe or persistent signs, or lower urinary tract disease that cannot be treated, to reduce the force and frequency of uncontrolled detrusor contractions.
• When to use it: In dogs, detrusor instability is treated at the per-kilogram dose in the table below, and a therapeutic trial is suggested where standard treatment for urethral sphincter mechanism incompetence has not worked and the pattern of urination is consistent with detrusor instability. Because documenting detrusor instability is difficult when confirmatory testing is unavailable, empirical treatment with continued monitoring of the clinical signs is reasonable.

Dosage (Reference)

Dog

In dogs, oxybutynin is used for refractory urinary incontinence associated with detrusor hyperreflexia.

Cat

In cats, oxybutynin is used for refractory urinary incontinence associated with detrusor hyperreflexia.

Warnings & Precautions

Due to its antimuscarinic effects, oxybutynin should be used cautiously in patients with conditions that may be worsened by reduced gastrointestinal motility, urinary retention, or other anticholinergic effects.

• Hypersensitivity: Contraindicated in patients with known hypersensitivity to oxybutynin or any component of the product.
• Gastrointestinal disorders: Use only when benefits outweigh risks in patients with obstructive GI tract disease, gastric retention, or conditions associated with decreased intestinal motility.
• Gastroesophageal disease: Use cautiously in patients with gastroesophageal reflux or hiatal hernia.
• Severe ulcerative colitis: Use only when benefits outweigh potential risks.
• Glaucoma: Avoid oxybutynin in patients with urinary retention, gastrointestinal obstruction, gastric retention, severe gastrointestinal hypomotility, or uncontrolled narrow-angle glaucoma. Other forms of glaucoma and cardiac disease—particularly tachyarrhythmias or congestive heart failure—require individualized risk–benefit assessment and close monitoring rather than blanket exclusion.
• Cardiac disease: Use oxybutynin cautiously in animals with cardiac disease, particularly tachyarrhythmias, mitral stenosis, or congestive heart failure, because its antimuscarinic effects may increase heart rate and worsen cardiac dysfunction. Use only when anticipated benefits outweigh risks, with appropriate cardiovascular monitoring.
• Myasthenia gravis: Use only when benefits outweigh risks.
• Hyperthyroidism: Use cautiously in affected patients.
• Prostatic hypertrophy: Should only be used when the benefits outweigh the risks.
• Urinary tract obstruction: Use cautiously in patients with urinary retention or other obstructive uropathies.
• Hepatic impairment: Use with caution in patients with liver dysfunction.
• Pregnancy: Safety has not been firmly established, although studies in a variety of laboratory animals have shown no teratogenic effect. Because safety has not been established in animals, this drug should only be used when the maternal benefits outweigh the potential risks to the offspring.
• Lactation: It is not known whether oxybutynin is excreted in milk. The drug may inhibit lactation, although no problems in nursing offspring have been documented.
• Heat exposure: Human product labeling warns that heat prostration – fever or heat stroke due to decreased sweating – can occur when oxybutynin is given at high environmental temperatures.
• Strength of the evidence: Animal data are limited, and a number of the contraindications listed here are reported in people rather than in animals. Results of clinical studies in animals are not available, and the doses used in dogs and cats are based on extrapolation from experience in people or on anecdotal experience in animals.
• Hypotension: Use with caution in patients with hypotension.

Drug Interactions

Most clinically relevant interactions with oxybutynin are related to additive anticholinergic effects, increased sedation, or altered drug concentrations. The interactions listed below have been reported or are theoretical, and unless otherwise noted concurrent use is not necessarily contraindicated – weigh the potential risks and monitor as appropriate.

• Amantadine: May increase the anticholinergic adverse effects of oxybutynin.
• Anticholinergic agents (e.g., atropine, propantheline, scopolamine, glycopyrrolate, antihistamines, tricyclic antidepressants): May intensify the anticholinergic effects of oxybutynin; isopropamide, hyoscyamine, disopyramide and procainamide belong to the same group.
• Azole antifungals (e.g., ketoconazole): May increase oxybutynin concentrations.
• Benzodiazepines (e.g., diazepam, midazolam): May exacerbate the sedating effects of oxybutynin.
• Beta-blockers (e.g., atenolol): Oxybutynin may increase atenolol bioavailability.
• CNS depressants (e.g., methocarbamol, trazodone): May enhance the sedating effects of oxybutynin.
• Macrolide antibiotics (e.g., erythromycin, clarithromycin): May increase oxybutynin concentrations.
• Opioids (e.g., buprenorphine, hydrocodone, morphine): May exacerbate the anticholinergic and sedating effects of oxybutynin.
• Desmopressin: Seizures have been reported in people when oxybutynin and desmopressin were given together.
• Metoclopramide: May antagonize the effect of metoclopramide on gastrointestinal motility.

Side Effects & Overdose

Side Effects

Adverse effects reported in dogs and cats are primarily related to the anticholinergic properties of oxybutynin.

• Diarrhea: Reported in small animals receiving oxybutynin.
• Constipation: Has been reported in small animals, and can occur with routine use.
• Urinary retention: Can occur secondary to its antimuscarinic effects.
• Hypersalivation: Reported in small animals.
• Sedation: May occur during treatment.
• Dry mouth or eyes: Potential anticholinergic effect.
• Tachycardia: May occur in some patients.
• Anorexia: Reported as a potential adverse effect.
• Vomiting: May occur during treatment.
• Weakness: Has been reported as a possible adverse effect.
• Mydriasis: May occur due to anticholinergic activity.
• Most common effects: Drowsiness or sleepiness, dry mouth and constipation are the most common side effects. Diarrhea and hypersalivation are also possible, and animals should have access to fresh water at all times.
• Nausea: May occur alongside vomiting and constipation, in keeping with the anticholinergic action.
• Other effects reported in people: Skin reactions, palpitations, confusion, hallucinations, agitation and somnolence have been reported in people. Human labeling advises watching for central effects particularly in the first few months of treatment or after a dose increase, and considering a dose reduction or stopping the drug if they occur.

Overdose

Oxybutynin overdose may produce severe neurologic, cardiovascular, and gastrointestinal effects. Massive overdoses can be life-threatening.

• CNS effects: Restlessness, excitement, and seizures may occur.
• Cardiovascular effects: Hyper- or hypotension, tachycardia, circulatory failure.
• Gastrointestinal effects: Nausea and vomiting may occur.
• Fever: Elevated body temperature may develop.
• Severe toxicity: Paralysis, coma, respiratory failure, and death may occur following massive overdoses.
• Treatment: Management includes limiting gastrointestinal absorption and providing supportive care.
• Physostigmine: IV physostigmine may be useful in overdose management.
• Plasma exchange: Therapeutic plasma exchange may be required in severe overdoses associated with paralysis or coma; oxybutynin is highly protein bound.
• Poison control: For a known or suspected overdose, consult a 24-hour poison control center that provides veterinary-specific advice.

Key Notes

Practical clinical points for the use of oxybutynin in dogs and cats:

• Primary action: Oxybutynin is classified as a urinary antispasmodic with both antimuscarinic and direct smooth muscle–relaxing properties.
• Target tissue: Its spasmolytic effects are most pronounced on the detrusor muscle of the urinary bladder.
• Bladder effects: In people with neurogenic bladders, oxybutynin increases bladder capacity and reduces uninhibited detrusor contractions.
• Formulations: Regular tablets and oral syrup are the formulations for which veterinary dosage recommendations are available.
• Extended-release products: No dosage recommendations for dogs or cats were identified for sustained-release tablets or transdermal gels/patches.
• Duration of action: In humans, the duration of action is reported to be approximately 6–10 hours after a dose.
• When it may not work: It increases urine retention by decreasing bladder spasms, so it may not be effective for incontinence caused by poor urethral sphincter tone. Where that is the cause, phenylpropanolamine and estrogens such as estriol are preferred.
• Extra-label use: There is no veterinary-licensed oxybutynin product; every regimen in dogs and cats is extra-label use of a human medicine.
• Monitoring: Monitor oxybutynin treatment by assessing urinary incontinence, voiding frequency, and ability to empty the bladder, together with adverse effects such as drowsiness, dry mouth, constipation, and urinary retention. Clinical improvement guides assessment of an empirical trial; no specific routine laboratory monitoring protocol is established.
• Pharmacokinetics: Rapidly and well absorbed from the gastrointestinal tract. Its elimination is not well documented, but it is apparently metabolized in the liver and excreted in the urine. It is highly protein bound.
• Secondary pharmacologic effects: Laboratory-animal studies also showed moderate antihistaminic, local anesthetic, mild analgesic, very weak mydriatic and antisialagogue (saliva-reducing) effects. Hypersalivation has been reported in small animals, while dry mouth or eyes are reported in people and may potentially occur in animals.
• Storage: Store tablets and oral solution in tight, light-resistant containers at 20 to 25°C; excursions between 15 and 30°C are permitted.