Ditropan Xl Information
Ditropan xl (Oxybutynin) Description
Ditropan xl (Oxybutynin) (oxybutynin chloride) is an antispasmodic, anticholinergic agent. Each Ditropan xl (Oxybutynin) 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) 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) Clinical Studies
Ditropan xl (Oxybutynin) (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) Indications And Usage
Ditropan xl (Oxybutynin) (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) Contraindications
Ditropan xl (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 XL is also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.
Ditropan xl (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 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) 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) 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) 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) 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)
Ditropan xl (Oxybutynin) Overdosage
The continuous release of oxybutynin from Ditropan xl (Oxybutynin) (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) Dosage And Administration
Ditropan xl (Oxybutynin) (oxybutynin chloride) must be swallowed whole with the aid of liquids, and must not be chewed, divided, or crushed.
Ditropan xl (Oxybutynin) may be administered with or without food.
Ditropan xl (Oxybutynin) How Supplied
Ditropan xl (Oxybutynin) (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) Extended Release Tablets are supplied in bottles of 100 tablets.
Ditropan xl (Oxybutynin)
