Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1772
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Ditropan (Tablet)
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Tablets:<br/>Adults: The usual dose is one 5-mg tablet two to three times a day.
The maximum recommended dose is one 5-mg tablet four times a day. A lower
starting dose of 2.5 mg two or three times a day is recommended for the frail
elderly.<br/>Pediatric patients over 5 years of
age: The usual dose is one 5-mg tablet two times a day. The maximum
recommended dose is one 5-mg tablet three times a day.<br/>Syrup:<br/>Adults: The usual dose is one teaspoon (5 mg/5 mL) of syrup two to
three times a day. The maximum recommended dose is one teaspoon (5 mg/5 mL)
of syrup four times a day. A lower starting dose of 2.5 mg two or three times
a day is recommended for the frail elderly.<br/>Pediatric patients over 5 years of
age: The usual dose is one teaspoon (5 mg/5 mL) of syrup two times
a day. The maximum recommended dose is one teaspoon (5 mg/5mL) of syrup three
times a day.
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| dailymed-instance:descripti... |
Each scored biconvex, engraved blue DITROPAN (oxybutynin
chloride) Tablet contains 5 mg of oxybutynin chloride. Each 5 mL of DITROPAN
Syrup contains 5 mg of oxybutynin chloride. Chemically, oxybutynin chloride
is d,l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate hydrochloride.
The empirical formula of oxybutynin chloride is CHNO���HCl.
The structural formula appears below: 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 Tablets
also contain calcium stearate, FD&C Blue #1 Lake, lactose, and microcrystalline
cellulose. DITROPAN Syrup also contains citric acid,
FD&C Green #3, glycerin, methylparaben, flavor, sodium citrate, sorbitol,
sucrose, and water. DITROPAN Tablets and Syrup are for
oral administration. Therapeutic Category: Antispasmodic,
anticholinergic.
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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 chloride increases bladder (vesical) capacity, diminishes
the frequency of uninhibited contractions of the detrusor muscle, and delays
the initial desire to void. Oxybutynin chloride thus decreases urgency and
the frequency of both incontinent episodes and voluntary urination. Antimuscarinic
activity resides predominately in the R-isomer. A metabolite, desethyloxybutynin,
has pharmacological activity similar to that of oxybutynin in in
vitro studies.<br/>Pharmacokinetics:<br/>Absorption: Following oral administration of DITROPAN, oxybutynin is
rapidly absorbed achieving Cwithin an hour, following which
plasma concentration decreases with an effective half-life of approximately
2 to 3 hours. The absolute bioavailability of oxybutynin is reported to be
about 6% (range 1.6 to 10.9%) for both the tablet and syrup. Wide interindividual
variation in pharmacokinetic parameters is evident following oral administration
of oxybutynin. The mean pharmacokinetic parameters
for R- and S-oxybutynin are summarized in Table 1. The plasma concentration-time
profiles for R- and S-oxybutynin are similar in shape; Figure 1 shows the
profile for R-oxybutynin. Figure 1. Mean R-oxybutynin
plasma concentrations following three doses of DITROPAN 5 mg administered
every 8 hours for 1 day in 23 healthy adult volunteers DITROPAN steady-state
pharmacokinetics were also studied in 23 pediatric patients with detrusor
overactivity associated with a neurological condition (e.g., spina bifida).
These pediatric patients were on DITROPAN tablets (n=11) with total daily
dose ranging from 7.5 mg to 15 mg (0.22 to 0.53 mg/kg) or DITROPAN syrup (n=12)
with total daily dose ranging from 5 mg to 22.5 mg (0.26 to 0.75 mg/kg). Overall,
most patients (86.9%) were taking a total daily DITROPAN dose between 10 mg
and 15 mg. Sparse sampling technique was used to obtain serum samples. When
all available data are normalized to an equivalent of 5 mg twicedaily DITROPAN,
the mean pharmacokinetic parameters derived for R- and S-oxybutynin and R-
and S-desethyloxybutynin are summarized in Table 2a (for tablet) and Table
2b (for syrup). The plasma-time concentration profile for R- and S-oxybutynin
are similar in shape; Figure 2 shows the profile for R-oxybutynin when all
available data are normalized to an equivalent of 5 mg twice daily. Figure 2. Mean steady-state
(��SD) R-oxybutynin plasma concentrations following administration of
total daily DITROPAN dose of 5 mg to 30 mg (0.21 mg/kg to 0.77 mg/kg) in children
5���15 years of age.���Plot represents all available data normalized
to the equivalent of DITROPAN 5 mg BID or TID at steady state<br/>Food Effects: Data in the literature suggests that oxybutynin solution
co-administered with food resulted in a slight delay in absorption and an
increase in its bioavailability by 25% (n=18).<br/>Distribution: Plasma concentrations of oxybutynin decline biexponentially
following intravenous or oral administration. The volume of distribution is
193 L after intravenous administration of 5 mg oxybutynin chloride.<br/>Metabolism: Oxybutynin is metabolized primarily by the cytochrome P450
enzyme systems, particularly CYP3A4 found mostly in the liver and gut wall.
Its metabolic products include phenylcyclohexylglycolic acid, which is pharmacologically
inactive, and desethyloxybutynin, which is pharmacologically active.<br/>Excretion: Oxybutynin is extensively metabolized by the liver, with
less than 0.1% of the administered dose excreted unchanged in the urine. Also,
less than 0.1% of the administered dose is excreted as the metabolite desethyloxybutynin.
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DITROPAN (oxybutynin chloride) Tablets are
supplied in bottles of 100 tablets (NDC 17314-9200-1). Blue scored tablets
(5 mg) are engraved with DITROPAN on one side with 92 and 00, separated by
a horizontal score, on the other side. DITROPAN Syrup
(5 mg/5 mL) is supplied in bottles of 16 fluid ounces (473 mL) (NDC 17314-9201-4). Pharmacist:
Dispense in tight, light-resistant container as defined in the USP. Store
at controlled room temperature 59���86��F (15���30��C).
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Central Nervous System Effects: Oxybutynin is associated with anticholinergic central nervous
system (CNS) effects .
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.<br/>General: 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 hypertrophy.<br/>Urinary Retention: DITROPAN should be administered with caution to patients
with clinically significant bladder outflow obstruction because of the risk
of urinary retention .<br/>Gastrointestinal Disorders: DITROPAN should be administered with caution to patients
with gastrointestinal obstructive disorders because of the risk of gastric
retention . 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 the disease. 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.<br/>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.<br/>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. This may be of
concern for drugs with a narrow therapeutic index. Mean
oxybutynin chloride plasma concentrations were approximately 3���4 fold
higher when DITROPAN 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., Cand AUC). The clinical relevance of such potential
interactions is not known. Caution should be used when such drugs are co-administered.<br/>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.<br/>Pregnancy: 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 hazards.<br/>Nursing Mothers: 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.<br/>Pediatric Use: The safety and efficacy of DITROPAN administration have been
demonstrated for pediatric patients 5 years of age and older . The safety and efficacy of DITROPAN Tablets
and DITROPAN Syrup were 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 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 H0
to 33 cm H0, and a reduction in the percentage of patients demonstrating
uninhibited detrusor contractions (of at least 15 cm H0) from
39% to 20%. At total daily doses ranging from 5 mg to
30 mg, treatment with DITROPAN Syrup was associated with an increase from
baseline in mean urine volume per catheterization from 113 mL to 133 mL, an
increase from baseline in mean urine volume after morning awakening from 143
mL to 165 mL, and an increase from baseline in the mean percentage of catheterizations
without a leaking episode from 34% to 63%. Urodynamic results were consistent
with these clinical results. Treatment with DITROPAN Syrup was associated
with an increase from baseline in maximum cystometric capacity from 192 mL
to 294 mL, a decreasefrom baseline in mean detrusor pressure at maximum cystometric
capacity from 46 cm H20 to 37 cm H20, and a reduction in the percentage of
patients demonstrating uninhibited detrusor contractions (of at least 15 cm
H0) from 67% to 28%. As there is insufficient
clinical data for pediatric populations under age 5, DITROPAN is not recommended
for this age group.<br/>Geriatric Use: 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.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.
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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 (e.g., restlessness, tremor, irritability,
convulsions, delirium, hallucinations), flushing, fever, dehydration, cardiac
arrhythmia, vomiting, and urinary retention. Other symptoms may include hypotension
or hypertension, respiratory failure, paralysis, and coma. 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.
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oxybutynin chloride
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Ditropan (Tablet)
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The safety and efficacy of DITROPAN (oxybutynin
chloride) was evaluated in a total of 199 patients in three clinical trials
comparing DITROPAN with DITROPAN XL (see Table 3).
These participants were treated with DITROPAN 5���20 mg/day for up to
6 weeks. Table 3 shows the incidence of adverse events judged by investigators
to be at least possibly related to treatment and reported by at least 5% of
patients. The most common adverse events reported by patients receiving
DITROPAN 5���20 mg/day were the expected side effects of anticholinergic
agents. The incidence of dry mouth was dose-related. In
addition, the following adverse events were reported by 1 to<5% of patients
using DITROPAN (5-20 mg/day) in all studies. Infections
and Infestations: nasopharyngitis, upper respiratory tract infection,
bronchitis, cystitis, fungal infection; Metabolism
and Nutrition Disorders: fluid retention; Psychiatric
Disorders: confusional state; Nervous
System Disorders: dysgeusia, sinus headache; Eye
Disorders: keratoconjunctivitis sicca, eye irritation; Cardiac
Disorders: palpitations, sinus arrhythmia; Vascular
Disorders: flushing; Respiratory, Thoracic
and Mediastinal Disorders: nasal dryness, cough, pharyngolaryngeal
pain, dry throat, sinus congestion, hoarseness, asthma, nasal congestion; Gastrointestinal Disorders: diarrhea, abdominal
pain, loose stools, flatulence, vomiting, abdominal pain upper, dysphagia,
aptyalism, eructation, tongue coated; Skin and
Subcutaneous Tissue Disorders: dry skin, pruritis; Musculoskeletal
and Connective Tissue Disorders: back pain, arthralgia, pain in
extremity, flank pain; Renal and Urinary Disorders
: dysuria, pollakiuria; General Disorders
and Administration Site Conditions: fatigue, edema peripheral, asthenia,
pain, thirst, edema; Investigations:
blood pressure increased, blood glucose increased, blood pressure decreased; Injury, Poisoning, and Procedural Complications:
fall.<br/>Postmarketing Surveillance: Because postmarketing adverse events are reported voluntarily
from a population of uncertain size, it is not always possible to reliably
estimate their frequency or establish a causal relationship to drug exposure.
The following additional adverse events have been reported from worldwide
postmarketing experience with DITROPAN: Psychiatric
Disorders: psychotic disorder, agitation, hallucinations; Nervous System Disorders: convulsions; Eye disorders: cycloplegia, mydriasis; Cardiac Disorders: tachycardia; Gastrointestinal
Disorders: decreased gastrointestinal motility; Skin
and Subcutaneous Tissue Disorders: rash, decreased sweating; Renal and Urinary Disorders: impotence; Reproductive system and breast disorders: Suppression
of lactation.
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DITROPAN (oxybutynin chloride) is indicated
for the relief of symptoms of bladder instability associated with voiding
in patients with uninhibited neurogenic or reflex neurogenic bladder (i.e.,
urgency, frequency, urinary leakage, urge incontinence, dysuria).
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Ditropan
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