Oxybutynin Chloride

INDICATIONS AND USAGE Oxybutynin Chloride Syrup 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).

DOSAGE AND ADMINISTRATION Syrup 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. 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/5 mL) of syrup three times a day.

CONTRAINDICATIONS Oxybutynin Chloride Syrup 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. Oxybutynin chloride is also contraindicated in patients who have demonstrated hypersensitivity to the drug substance or other components of the product.

ADVERSE REACTIONS The safety and efficacy of Oxybutynin Chloride Syrup was evaluated in a total of 199 patients in three clinical trials comparing oxybutynin chloride with oxybutynin chloride extended release tablets (see Table 3 ). These participants were treated with oxybutynin chloride 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. Table 3 Incidence (%) of Adverse Events Reported by ≥ 5% of Patients Using Oxybutynin Chloride (5-20 mg/day) Body System Adverse Event Oxybutynin Chloride (5-20 MG/DAY) (N=199) Infections and Infestations Urinary tract infection 6.5% Psychiatric Disorders Insomnia Nervousness 5.5% 6.5% Nervous System Disorders Dizziness Somnolence Headache 16.6% 14.0% 7.5% Eye Disorders Blurred vision 9.6% Gastrointestinal Disorders Dry mouth Constipation Nausea Dyspepsia 71.4% 15.1% 11.6% 6.0% Renal and Urinary Disorders Urinary Hesitation Urinary Retention 8.5% 6.0% The most common adverse events reported by patients receiving oxybutynin chloride 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 oxybutynin chloride (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. 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 oxybutynin chloride: Psychiatric Disorders: psychotic disorder, agitation, hallucinations; memory impairment; Nervous System Disorders: convulsions; Eye disorders: cycloplegia, mydriasis; Cardiac Disorders: tachycardia; QT interval prolongation; 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. General Disorders and Administration Site Conditions: hypersensitivity reactions, including angioedema with airway obstruction, urticaria, and face edema; rare anaphylactic reactions requiring hospitalization for emergency treatment.

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 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., Cmax and AUC). The clinical relevance of such potential interactions is not known. Caution should be used when such drugs are co-administered.

DESCRIPTION Chemically, oxybutynin chloride is d,l (racemic) 4-diethylamino-2-butynyl phenylcyclohexylglycolate hydrochloride. The empirical formula of oxybutynin chloride is C 22 H 31 NO 3 •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. Each 5 mL, for oral administration, contains 5 mg of oxybutynin chloride. In addition, the following inactive ingredients are present: citric acid, FD&C Green #3, raspberry flavor, glycerin, methylparaben, propylene glycol, sodium citrate, sorbitol solution, sucrose, and water. Therapeutic Category: Antispasmodic, anticholinergic. Structure of 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.

HOW SUPPLIED OXYBUTYNIN CHLORIDE SYRUP USP (5 mg/5 mL) is supplied in bottles of one pint (473 mL). OXYBUTYNIN CHLORIDE SYRUP USP (5 mg/5 mL) is a light bluish-green liquid with a characteristic raspberry flavor. NDC 54838-510-80 Pharmacist: Dispense in tight, light-resistant container as defined in the USP. Store at controlled room temperature 59°F to 86°F (15°C to 30°C).