Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety and efficacy of DITROPAN XL® (oxybutynin chloride) were 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 reactions 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).
Table 3 : Incidence (%) of Adverse Reactions Reported by ≥ 5% of Patients Using DITROPAN XL® (530 mg/day) and % of Corresponding Adverse Reactions in Two Fixed-Dose (10 mg/day) Studies
|Body System||Adverse Reactions||DITROPAN XL® 5-30 mg/day
|DITROPAN XL® 10 mg/day
|Special senses||blurred vision||8||1|
|Urogenital||urinary tract infection||5||5|
The most common adverse reactions 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 reactions 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 reactions causing early discontinuation of study medication was nausea (1.9%), while discontinuation due to dry mouth was 1.2%.
In addition, the following adverse reactions were reported by ≥ 1 to < 5% of all patients who received DITROPAN XL® in the 6 adjustable and fixed-dose efficacy and safety studies. Psychiatric disorders: depression, nervousness, insomnia, confusional state; Nervous System Disorders: dysgeusia; Cardiac disorders: palpitations; Vascular disorders: hypertension; Respiratory, thoracic and mediastinal disorders: nasal dryness, cough, oropharyngeal pain, dry throat; Gastrointestinal Disorders: gastroesophageal reflux disease, abdominal pain, flatulence, vomiting; Skin and subcutaneous tissue disorders: dry skin, pruritus; Renal and urinary disorders: urinary retention, urinary hesitation, dysuria; General disorders and administration site conditions: fatigue, edema peripheral, chest pain.
The following adverse reactions were reported by < 1% of DITROPAN XL®-treated patients and at a higher incidence than placebo in clinical trials: Metabolism and Nutrition Disorders: anorexia, fluid retention; Vascular disorders: hot flush; Respiratory, thoracic and mediastinal disorders: dysphonia; Gastrointestinal Disorders: dysphagia, frequent bowel movements; General disorders and administration site conditions: chest discomfort, thirst.
The following additional adverse drug reactions have been reported from worldwide postmarketing experience with DITROPAN XL®. 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.
Psychiatric Disorders: psychotic disorder, agitation, hallucinations, memory impairment; Nervous System Disorders: convulsions; Eye Disorders: glaucoma; Cardiac Disorders: arrhythmia, tachycardia, QT interval prolongation; Vascular Disorders: flushing; Skin and Subcutaneous Tissue Disorders: rash; Renal and Urinary Disorders: impotence; 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; Injury, poisoning and procedural complications: fall.
Additional adverse events reported with some other oxybutynin chloride formulations include: cycloplegia, mydriasis, and suppression of lactation.