Central Nervous System Effects
Oxybutynin is associated with anticholinergic central nervous system (CNS) effects (See Adverse Reactions). A variety of CNS anticholinergic effects have been reported, including hallucinations, agitation, confusion and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly in the first few months after beginning treatment or increasing the dose. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.
Oxybutynin Chloride Tablets should be used with caution in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.
Oxybutynin chloride should be used with caution in the frail elderly, in patients with hepatic or renal impairment, and in patients with myasthenia gravis.
Oxybutynin chloride may aggravate the symptoms of hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, hiatal hernia, tachycardia, hypertension, myasthenia gravis, and prostatic hypertrophy.
Oxybutynin chloride should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention (see CONTRAINDICATIONS).
Oxybutynin chloride should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention (see CONTRAINDICATIONS).
Administration of oxybutynin chloride to patients with ulcerative colitis may suppress intestinal motility to the point of producing a paralytic ileus and precipitate or aggravate toxic megacolon, a serious complication of the disease.
Oxybutynin chloride, like other anticholinergic drugs, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis, and intestinal atony.
Oxybutynin chloride should be used with caution in patients who have gastroesophageal reflux and/or who are concurrently taking drugs (such as bisphosphonates) that can cause or exacerbate esophagitis.
Information for Patients
Patients should be informed that heat prostration (fever and heat stroke due to decreased sweating) can occur when anticholinergics such as oxybutynin chloride are administered in the presence of high environmental temperature.
Because anticholinergic agents such as oxybutynin may produce drowsiness (somnolence), or blurred vision, patients should be advised to exercise caution.
Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents such as oxybutynin.
The concomitant use of oxybutynin with other anticholinergic drugs or with other agents which produce dry mouth, constipation, somnolence (drowsiness), and/or other anticholinergic-like effects may increase the frequency and/or severity of such effects.
Anticholinergic agents may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. This may be of concern for drugs with a narrow therapeutic index.
Mean oxybutynin chloride plasma concentrations were approximately 3-4 fold higher when oxybutynin chloride was administered with ketoconazole, a potent CYP3A4 inhibitor.
Other inhibitors of the cytochrome P450 3A4 enzyme system, such as antimycotic agents (e.g., itraconazole and miconazole) or macrolide antibiotics (e.g., erythromycin and clarithromycin), may alter oxybutynin mean pharmacokinetic parameters (i.e., Cmax and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.
Carcinogenesis, Mutagenesis, Impairment of Fertility
A 24-month study in rats at dosages of oxybutynin chloride of 20, 80, and 160 mg/kg/day showed no evidence of carcinogenicity. These doses are approximately 6, 25, and 50 times the maximum human exposure, based on surface area.
Oxybutynin chloride showed no increase of mutagenic activity when tested in Schizosaccharomyces pompholiciformis, Saccharomyces cerevisiae and Salmonella typhimurium test systems.
Reproduction studies using oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no definite evidence of impaired fertility.
Category B. Reproduction studies using oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no definite evidence of impaired fertility or harm to the animal fetus. The safety of oxybutynin chloride administered to women who are or who may become pregnant has not been established. Therefore, oxybutynin chloride should not be given to pregnant women unless, in the judgment of the physician, the probable clinical benefits outweigh the possible hazards.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when oxybutynin chloride is administered to a nursing woman.
The safety and efficacy of oxybutynin chloride administration have been demonstrated for pediatric patients 5 years of age and older (see DOSAGE AND ADMINISTRATION).
The safety and efficacy of oxybutynin chloride tablets and oxybutynin chloride syrup was studied in 30 and in 26 children, respectively, in a 24-week, open-label trial. Patients were aged 5-15 years, all had symptoms of detrusor overactivity in association with a neurological condition (e.g., spina bifida), all used clean intermittent catheterization, and all were current users of oxybutynin chloride. Study results demonstrated that the administration of oxybutynin chloride was associated with improvement in clinical and urodynamic parameters.
At total daily doses ranging from 5 mg to 15 mg, treatment with oxybutynin chloride tablets was associated with an increase from baseline in mean urine volume per catheterization from 122 mL to 145 mL, an increase from baseline in mean urine volume after morning awakening from 148 mL to 168 mL, and an increase from baseline in the mean percentage of catheterizations without a leaking episode from 43% to 61%. Urodynamic results in these patients were consistent with the clinical results. Treatment with oxybutynin chloride tablets was associated with an increase from baseline in maximum cystometric capacity from 230 mL to 279 mL, a decrease from baseline in mean detrusor pressure at maximum cystometric capacity from 36 cm H2O to 33 cm H2O, and a reduction in the percentage of patients demonstrating uninhibited detrusor contractions (of at least 15 cm H2O) from 39% to 20%.
As there is insufficient clinical data for pediatric patients under age 5, oxybutynin chloride is not recommended for this age group.
Clinical studies of oxybutynin chloride did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between healthy elderly and younger patients; however, a lower initial starting dose of 2.5 mg given 2 or 3 times a day has been recommended for the frail elderly due to a prolongation of the elimination half-life from 2-3 hours to 5 hours.2,3,4 In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.