Ditropan Information
Ditropan (Oxybutynin) Description
Each scored biconvex, engraved blue Ditropan (Oxybutynin) (oxybutynin chloride) Tablet 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 (Oxybutynin) Tablets also contain calcium stearate, FD&C Blue #1 Lake, lactose, and microcrystalline cellulose.
Ditropan (Oxybutynin) Tablets are for oral administration.
Therapeutic Category: Antispasmodic, anticholinergic.
Ditropan (Oxybutynin) 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 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 studies.
Ditropan (Oxybutynin) Clinical Studies
Ditropan (Oxybutynin) was well tolerated in patients administered the drug in controlled studies of 30 days' duration and in uncontrolled studies in which some of the patients received the drug for 2 years.
Ditropan (Oxybutynin) Indications And Usage
Ditropan (Oxybutynin) (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).
Ditropan (Oxybutynin) Contraindications
Ditropan (Oxybutynin) (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 (Oxybutynin) is also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.
Ditropan (Oxybutynin) 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 (Oxybutynin) should be used with caution in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.
Ditropan (Oxybutynin) (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 (Oxybutynin) may aggravate the symptoms of hyperthyroidism, coronary heart disease, congestive heart failure, cardiac arrhythmias, hiatal hernia, tachycardia, hypertension, myasthenia gravis, and prostatic hypertrophy.
Ditropan (Oxybutynin) should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention (see).
Administration of Ditropan (Oxybutynin) 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 (Oxybutynin) , 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 (Oxybutynin) 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.
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 Ditropan (Oxybutynin) 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 using oxybutynin chloride in the hamster, rabbit, rat, and mouse have shown no definite evidence of impaired fertility.
The safety and efficacy of Ditropan (Oxybutynin) administration have been demonstrated for pediatric patients 5 years of age and older (see).
The safety and efficacy of Ditropan (Oxybutynin) Tablets were studied in 30 children 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 (Oxybutynin) was associated with improvement in clinical and urodynamic parameters.
At total daily doses ranging from 5 mg to 15 mg, treatment with Ditropan (Oxybutynin) 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 (Oxybutynin) 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%.
As there is insufficient clinical data for pediatric populations under age 5, Ditropan (Oxybutynin) is not recommended for this age group.
Ditropan (Oxybutynin) Adverse Reactions
The safety and efficacy of Ditropan (Oxybutynin) (oxybutynin chloride) was evaluated in a total of 199 patients in three clinical trials. These participants were treated with Ditropan (Oxybutynin) 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 (Oxybutynin) 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
Ditropan (Oxybutynin) Overdosage
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.
Ditropan (Oxybutynin) Dosage And Administration
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.
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.
Ditropan (Oxybutynin) How Supplied
Ditropan (Oxybutynin) (oxybutynin chloride) Tablets are supplied in bottles of 100 tablets (NDC 17314-9200-1). Blue scored tablets (5 mg) are engraved with Ditropan (Oxybutynin) on one side with 92 and 00, separated by a horizontal score, on the other side.
Pharmacist: Dispense in tight, light-resistant container as defined in the USP.
Store at controlled room temperature 59–86°F (15–30°C).
Ditropan (Oxybutynin) References
Manufactured by sanofi-aventis U.S. LLC, Kansas City, MO 64137.
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633-20-616-4
Ditropan (Oxybutynin) Principal Display Panel - Tablet Bottle
