Ditropan Xl Information
Ditropan xl (Oxybutynin chloride) Description
Ditropan xl (Oxybutynin chloride) is an
antispasmodic, anticholinergic agent. Each Ditropan xl (Oxybutynin chloride) Extended Release Tablet
contains 5 mg, 10 mg, or 15 mg of oxybutynin chloride USP, formulated as a
once-a-day controlled-release tablet for oral administration. Oxybutynin chloride
is administered as a racemate of R- and S-enantiomers.
Chemically,
oxybutynin chloride is d,l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate
hydrochloride. The empirical formula of oxybutynin chloride is CHNO•
HCl.
Its structural formula is:
Oxybutynin chloride is
a white crystalline solid with a molecular weight of 393.9. It is readily
soluble in water and acids, but relatively insoluble in alkalis.
DITROPAN
XL also contains the following inert ingredients: cellulose acetate, hypromellose,
lactose, magnesium stearate, polyethylene glycol, polyethylene oxide, synthetic
iron oxides, titanium dioxide, polysorbate 80, sodium chloride, and butylated
hydroxytoluene.
Ditropan xl (Oxybutynin chloride) Clinical Pharmacology
Oxybutynin chloride exerts a direct antispasmodic effect
on smooth muscle and inhibits the muscarinic action of acetylcholine on smooth
muscle. Oxybutynin chloride exhibits only one-fifth of the anticholinergic
activity of atropine on the rabbit detrusor muscle, but four to ten times
the antispasmodic activity. No blocking effects occur at skeletal neuromuscular
junctions or autonomic ganglia (antinicotinic effects).
Oxybutynin
chloride relaxes bladder smooth muscle. In patients with conditions characterized
by involuntary bladder contractions, cystometric studies have demonstrated
that oxybutynin increases bladder (vesical) capacity, diminishes the frequency
of uninhibited contractions of the detrusor muscle, and delays the initial
desire to void. Oxybutynin thus decreases urgency and the frequency of both
incontinent episodes and voluntary urination.
Antimuscarinic
activity resides predominantly in the R-isomer. A metabolite, desethyloxybutynin,
has pharmacological activity similar to that of oxybutynin in studies.
Ditropan xl (Oxybutynin chloride) Clinical Studies
Ditropan xl (Oxybutynin chloride) was evaluated
for the treatment of patients with overactive bladder with symptoms of urge
urinary incontinence, urgency, and frequency in three controlled studies and
one open label study. The majority of patients were Caucasian (89.0%) and
female (91.9%) with a mean age of 59 years (range, 18 to 98 years). Entry
criteria required that patients have urge or mixed incontinence (with a predominance
of urge) as evidenced by ≥ 6 urge incontinence episodes per week and≥ 10 micturitions per day. Study 1 was a fixed dose escalation design,
whereas the other studies used a dose adjustment design in which each patient's
final dose was adjusted to a balance between improvement of incontinence symptoms
and tolerability of side effects. Controlled studies included patients known
to be responsive to oxybutynin or other anticholinergic medications, and these
patients were maintained on a final dose for up to 2 weeks.
The
efficacy results for the three controlled trials are presented in the following
tables and figures.
Ditropan xl (Oxybutynin chloride) Indications And Usage
Ditropan xl (Oxybutynin chloride) is a once-daily
controlled-release tablet indicated for the treatment of overactive bladder
with symptoms of urge urinary incontinence, urgency, and frequency.
DITROPAN
XL is also indicated in the treatment of pediatric patients aged 6 years and
older with symptoms of detrusor overactivity associated with a neurological
condition (e.g., spina bifida).
Ditropan xl (Oxybutynin chloride) Contraindications
Ditropan xl (Oxybutynin chloride) is contraindicated
in patients with urinary retention, gastric retention and other severe decreased
gastrointestinal motility conditions, uncontrolled narrow-angle glaucoma and
in patients who are at risk for these conditions.
DITROPAN
XL is also contraindicated in patients who have demonstrated hypersensitivity
to the drug substance or other components of the product.
Ditropan xl (Oxybutynin chloride) Precautions
Oxybutynin is associated with anticholinergic central nervous
system (CNS) effects (See ).
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
XL should be used with caution in patients with preexisting dementia treated
with cholinesterase inhibitors due to the risk of aggravation of symptoms.
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.
Patients should be informed
that Ditropan xl (Oxybutynin chloride) should be swallowed whole with the aid of liquids. Patients
should not chew, divide, or crush tablets. The medication is contained within
a nonabsorbable shell designed to release the drug at a controlled rate. The
tablet shell is eliminated from the body; patients should not be concerned
if they occasionally notice in their stool something that looks like a tablet.
DITROPAN
XL should be taken at approximately the same time each day.
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 2 fold higher
when Ditropan xl (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., C and AUC). The clinical relevance of such
potential interactions is not known. Caution should be used when such drugs
are co-administered.
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 , and test systems.
Reproduction studies
with oxybutynin chloride in the mouse, rat, hamster, and rabbit showed no
definite evidence of impaired fertility.
The safety and efficacy of Ditropan xl (Oxybutynin chloride) were studied in 60
children in a 24-week, open-label trial. Patients were aged 6-15 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
administration of Ditropan xl (Oxybutynin chloride) 5 to 20 mg/day was associated with an increase
from baseline in mean urine volume per catheterization from 108 mL to 136
mL, an increase from baseline in mean urine volume after morning awakening
from 148 mL to 189 mL, and an increase from baseline in the mean percentage
of catheterizations without a leaking episode from 34% to 51%.
Urodynamic
results were consistent with clinical results. Administration of DITROPAN
XL resulted in an increase from baseline in mean maximum cystometric capacity
from 185 mL to 254 mL, a decrease from baseline in mean detrusor pressure
at maximum cystometric capacity from 44 cm HO to 33 cm HO,
and a reduction in the percentage of patients demonstrating uninhibited detrusor
contractions (of at least 15 cm HO) from 60% to 28%.
DITROPAN
XL is not recommended in pediatric patients who can not swallow the tablet
whole without chewing, dividing, or crushing, or in children under the age
of 6 (See ).
Ditropan xl (Oxybutynin chloride)
Ditropan xl (Oxybutynin chloride) Overdosage
The continuous release of oxybutynin from Ditropan xl (Oxybutynin chloride) (oxybutynin
chloride) should be considered in the treatment of overdosage. Patients should
be monitored for at least 24 hours. Treatment should be symptomatic and supportive.
Activated charcoal as well as a cathartic may be administered.
Overdosage
with oxybutynin chloride has been associated with anticholinergic effects
including central nervous system excitation, flushing, fever, dehydration,
cardiac arrhythmia, vomiting, and urinary retention.
Ingestion
of 100 mg oxybutynin chloride in association with alcohol has been reported
in a 13-year-old boy who experienced memory loss, and a 34-year-old woman
who developed stupor, followed by disorientation and agitation on awakening,
dilated pupils, dry skin, cardiac arrhythmia, and retention of urine. Both
patients fully recovered with symptomatic treatment.
Ditropan xl (Oxybutynin chloride) Dosage And Administration
Ditropan xl (Oxybutynin chloride) must be
swallowed whole with the aid of liquids, and must not be chewed, divided,
or crushed.
Ditropan xl (Oxybutynin chloride) may be administered with or
without food.
Ditropan xl (Oxybutynin chloride) How Supplied
Ditropan xl (Oxybutynin chloride) Extended
Release Tablets are available in three dosage strengths, 5 mg (pale yellow),
10 mg (pink), and 15 mg (gray) and are imprinted with "5 XL", "10 XL", or
"15 XL". Ditropan xl (Oxybutynin chloride) Extended Release Tablets are supplied in bottles of 100
tablets.
Ditropan xl (Oxybutynin chloride)
