SIDE EFFECTS
Adverse Events with DITROPAN® XL
The safety and efficacy of DITROPANÒ XL was evaluated
in a total of 580 participants who received DITROPAN®
XL in clinical trials (429 patients, 151 healthy volunteers).
These participants were treated with 5-30 mg/day for up
to 4.5 months. Safety information is provided for 429
patients from three controlled clinical studies and one
open label study (Table 2). The adverse events are reported
regardless of causality.
Table 2 Incidence (%) of Adverse
Events Reported by ³ 5% of Patients Using DITROPANÒ
XL (5-30 mg/day)
|
Body System
|
Adverse Event
|
DITROPANÒ XL
5-30 mg/day (n=429)
|
|
General
|
headache |
9.8
|
| |
asthenia |
6.8
|
| |
pain |
6.8
|
|
Digestive
|
dry mouth
|
60.8
|
| |
constipation
|
13.1
|
| |
diarrhea |
9.1
|
| |
nausea |
8.9
|
| |
dyspepsia
|
6.8
|
|
Nervous
|
somnolence
|
11.9
|
| |
dizziness
|
6.3
|
|
Respiratory
|
rhinitis |
5.6
|
|
Special senses
|
blurred vision
|
7.7
|
| |
dry eyes |
6.1
|
|
Urogenital
|
urinary tract
infection |
5.1
|
The most common adverse events reported by patients receiving
5-30 mg/day DITROPANÒ XL were the expected side effects
of anticholinergic agents. The incidence of dry mouth was
dose-related.
The discontinuation rate for all adverse events was 6.8%.
The most frequent adverse event causing early discontinuation
of study medication was nausea (1.9%), while discontinuation
due to dry mouth was 1.2%.
In addition, the following adverse events were reported
by 2 to < 5% of patients using DITROPANÒ XL
(5-30 mg/day) in all studies. General: abdominal pain,
dry nasal and sinus mucous membranes, accidental injury,
back pain, flu syndrome; Cardiovascular: hypertension,
palpitation, vasodilatation; Digestive: flatulence, gastroesophageal
reflux; Musculoskeletal: arthritis; Nervous: insomnia,
nervousness, confusion; Respiratory: upper respiratory
tract infection, cough, sinusitis, bronchitis, pharyngitis;
Skin: dry skin, rash; Urogenital: impaired urination (hesitancy),
increased post void residual volume, urinary retention,
cystitis.
Adverse Events with Oxybutynin Chloride
Other adverse events have been reported with oxybutynin
chloride: tachycardia, hallucinations, cycloplegia, mydriasis,
impotence, and suppression of lactation.
DRUG INTERACTIONS
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.
Pharmacokinetic studies with patients concomitantly receiving
cytochrome P450 enzyme inhibitors, such as antimycotic
agents (e.g. ketoconazole, itraconazole, and miconazole)
or macrolide antibiotics (e.g. erythromycin and clarithromycin),
have not been performed.
No specific drug-drug interaction studies have been performed
with DITROPAN® XL.
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 with oxybutynin chloride in the
mouse, rat, hamster, and rabbit showed no definite evidence
of impaired fertility.
Pregnancy: Teratogenic Effects
Pregnancy Category B
Reproduction studies with oxybutynin chloride in the
mouse, rat, hamster, and rabbit showed no definite evidence
of impaired fertility or harm to the animal fetus. The
safety of DITROPAN® XL administration to women who
are or who may become pregnant has not been established.
Therefore, DITROPAN® XL should not be given to pregnant
women unless, in the judgment of the physician, the probable
clinical benefits outweigh the possible hazards.
Nursing Mothers
It is not known whether oxybutynin is excreted in human
milk. Because many drugs are excreted in human milk, caution
should be exercised when DITROPAN® XL is administered
to a nursing woman.
Pediatric Use
The safety and efficacy of DITROPAN® XL in pediatric
patients have not been established.
Geriatric Use
The rate and severity of anticholinergic effects reported
by patients less than 65 years old and those 65 years and
older were similar (See CLINICAL PHARMACOLOGY, Pharmacokinetics,
Special Populations: Gender). |
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