Adverse Events with DITROPAN XL

The safety and efficacy of DITROPAN XL® (oxybutynin chloride) was evaluated in a total of 580 participants who received DITROPAN XL in 4 clinical trials (429 patients) and four pharmacokinetic studies (151 healthy volunteers). The 429 patients were treated with 5-30 mg/day for up to 4.5 months. Three of the 4 clinical trials allowed dose adjustments based on efficacy and adverse events and one was a fixed dose escalation design. Safety information is provided for 429 patients from these three controlled clinical studies and one open label study in the first column of Table 3 below.

Adverse events from two additional fixed dose, active controlled, 12 week treatment duration, postmarketing studies, in which 576 patients were treated with DITROPAN XL 10 mg/day, are also listed in Table 3 (second column). The adverse events are reported regardless of causality.

Table 3: Incidence (%) of Adverse Events Reported by ≥ 5% of Patients Using DITROPAN XL (5-30 mg/day) and % of Corresponding Adverse Events in Two Fixed Dose (10mg/day) Studies

The most common adverse events reported by the 429 patients receiving 5-30 mg/day DITROPAN XL were the expected side effects of anticholinergic agents. The incidence of dry mouth was dose-related.

The discontinuation rate for all adverse events was 6.8% in the 429 patients from the 4 studies of efficacy and safety who received 5-30 mg/day. The most frequent adverse event causing early discontinuation of study medication was nausea (1.9%), while discontinuation due to dry mouth was 1.2%.

In addition, the following adverse events were reported by ≥ 1 to < 5% of all patients who received DITROPAN XL in the 6 adjustable and fixed dose efficacy and safety studies. Infections and infestations: nasopharyngitis, upper respiratory tract infection, sinusitis, bronchitis, cystitis;Psychiatric disorders: insomnia, depression, nervousness, confusional state; Nervous System Disorders: dysgeusia; Cardiac disorders: palpitations; Vascular disorders: hypertension; Respiratory, thoracic and mediastinal disorders: nasal dryness, cough, pharyngolaryngeal pain, dry throat; Gastrointestinal Disorders: gastroesophageal reflux disease, abdominal pain, loose stools, flatulence, vomiting; Skin and subcutaneous tissue disorders: dry skin, pruritis; Musculoskeletal and connective tissue disorders: back pain, arthralgia, pain in extremity; Renal and urinary disorders: urinary retention, urinary hesitation, dysuria; General disorders and administration site conditions: fatigue, edema peripheral, asthenia, chest pain; Investigations: blood pressure increased.

Postmarketing Surveillance

Because postmarketing reactions 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 drug reactions have been reported from worldwide postmarketing experience with DITROPAN XL:Psychiatric Disorders: psychotic disorder, agitation, hallucinations; Nervous System Disorders: convulsions; Cardiac Disorders: arrhythmia; tachycardia; Vascular Disorders: flushing; Skin and Subcutaneous Tissue Disorders: rash; Renal and Urinary Disorders: impotence; Injury, poisoning and procedural complications: fall.

Additional adverse events reported with some other oxybutynin chloride formulations include: cycloplegia, mydriasis, and suppression of lactation.

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 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.

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