Angioedema of the face, lips, tongue and/or larynx has been
reported with oxybutynin. In some cases, angioedema occurred after the first
dose. Angioedema associated with upper airway swelling may be life-threatening.
If involvement of the tongue, hypopharynx, or larynx occurs, oxybutynin should
be promptly discontinued and appropriate therapy and/or measures necessary to
ensure a patent airway should be promptly provided.
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.
DITROPAN should be used with caution in patients with
preexisting dementia treated with cholinesterase inhibitors due to the risk of
aggravation of symptoms.
DITROPAN® (oxybutynin chloride) should be
used with caution in the frail elderly, in patients with hepatic or renal
impairment, and in patients with myasthenia gravis.
DITROPAN may aggravate the symptoms of hyperthyroidism,
coronary heart disease, congestive heart failure, cardiac arrhythmias, hiatal
hernia, tachycardia, hypertension, myasthenia gravis, and prostatic
DITROPAN should be administered with caution to patients
with clinically significant bladder outflow obstruction because of the risk of
urinary retention (see CONTRAINDICATIONS).
DITROPAN should be administered with caution to patients
with gastrointestinal obstructive disorders because of the risk of gastric
retention (see CONTRAINDICATIONS).
Administration of DITROPAN 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
DITROPAN, 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.
DITROPAN 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.
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
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
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 DITROPAN administered
to women who are or who may become pregnant has not been established.
Therefore, DITROPAN should not be given to pregnant women unless, in the
judgment of the physician, the probable clinical benefits outweigh the possible
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
DITROPAN is administered to a nursing woman.
The safety and efficacy of DITROPAN administration have been
demonstrated for pediatric patients 5 years of age and older (see DOSAGE AND
The safety and efficacy of DITROPAN Tablets were studied in
30 children in a 24week, 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 DITROPAN was associated with improvement in clinical
and urodynamic parameters.
At total daily doses ranging from 5 mg to 15 mg, treatment
with DITROPAN 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 DITROPAN 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
populations under age 5, DITROPAN is not recommended for this age group.
Clinical studies of DITROPAN 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
2. Hughes KM et al. Measurement of oxybutynin and its
N-desethyl metabolite in plasma, and its application to pharmacokinetic studies
in young, elderly and frail elderly volunteers. Xenobiotica. 1992; 22 (7):
3. Ouslander J et al. Pharmacokinetics and Clinical Effects
of Oxybutynin in Geriatric Patients. J. Urol. 1988; 140: 47-50.
4. Yarker Y et al. Oxybutynin: A review of its
Pharmacodynamic and Pharmacokinetic Properties, and its Therapeutic Use in
Detrusor Instability. Drugs & Aging. 1995; 6(3): 243-262.