Oxybutynin

Abstract: Oxybutynin possesses anticholinergic and spasmolytic properties, which together form the basis for its use as a therapeutic option in patients with overactive detrusor function--either idiopathic detrusor instability (DI) or detrusor hyperreflexia. Of the symptoms of detrusor overactivity, urge incontinence is often the most distressing to the patient. Urge incontinence and other subjective parameters (urinary frequency, urgency) improve in tandem with objective (cystometric) measures (maximum detrusor pressure during filling, volume at first desire to void, maximum bladder capacity) in ambulatory, including elderly, patients treated with oxybutynin. However, on the basis of results of limited investigations, the drug appears ineffective in elderly institutionalised individuals. Relative to other anticholinergic drugs, oxybutynin appears at least as effective as propantheline and similar in efficacy to propiverine in small trials, although these results are not definitive. Further investigation of intravesical oxybutynin may lead to this route becoming an option in patients with pre-existing catheters. Adverse effects--dry mouth, constipation, blurred vision--related to the anticholinergic activity of oxybutynin occur frequently and can be sufficiently troublesome to necessitate treatment discontinuation in up to 25% of patients, depending on the dosage. Increases in residual urine volume suggesting urinary retention (undesirable in patients with idiopathic DI), also can develop in some oxybutynin recipients. In summary, oxybutynin is one of the few drugs proven to be beneficial in some patients with overactive detrusor function. Despite the occurrence of unwanted anticholinergic effects in many patients, and apparent lack of efficacy in the elderly institutionalised population, oxybutynin should be considered for the drug of first choice in patients with detrusor overactivity, including the elderly ambulatory population, when pharmacological therapy is indicated.

Abstract: Objective To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder. Patients and methods A randomized, double-blind, placebo-controlled, parallel group, multinational phase-III study was conducted in urology and gynaecology clinics in the UK, Republic of Ireland and Sweden. The study enrolled 293 patients with urodynamically confirmed bladder overactivity, increased frequency of micturition (≥8 micturitions/24 h) and symptoms of urgency and/or urge incontinence (≥1 episode/24 h). Patients received either tolterodine (2 mg twice daily) or oxybutynin (5 mg three times daily) or placebo. Doses could be reduced, to prevent withdrawal, to 1 mg or 2.5 mg, respectively. The main outcome measures were the mean change from baseline in frequency of micturition/24 h, the number of incontinent episodes/24 h and volume voided per micturition. Results After 12 weeks’ treatment, the mean frequency of micturition decreased by 21% and 19.5% in those receiving tolterodine (n=118) and oxybutynin (n=118), respectively, and by 10.5% in those on placebo (n=57). Among those with urge incontinence at baseline (75% of patients), the mean number of incontinent episodes decreased by 47%, 71% and 19%, respectively, in those receiving tolterodine, oxybutynin and placebo. The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent. There was also a comparable increase in mean volume voided per micturition in the tolterodine (27%) and oxybutynin groups (31%), compared with 7% in the placebo group. Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo. In the oxybutynin group, more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events. Despite dose reduction, the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin (2.5 mg three times daily) than in patients who remained on tolterodine 2 mg twice daily. Conclusion Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity. Tolterodine was better tolerated than oxybutynin, particularly with respect to the frequency and intensity of dry mouth, but had comparable clinical efficacy. The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder.

Abstract: Objective To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder. Patients and Methods The OPERA (Overactive bladder: Performance of Extended Release Agents) trial was a randomized, double-blind, active-control study performed at 71 US study centers from November 21, 2000, to October 18, 2001. Extended-release formulations of oxybutynin at 10 mg/d or tolterodine at 4 mg/d were given for 12 weeks to women with 21 to 60 urge urinary incontinence (UUI) episodes per week and an average of 10 or more voids per 24 hours. Episodes of UUI (primary end point), total (urge and nonurge) incontinence, and micturition were recorded in 24-hour urinary diaries at baseline and at weeks 2, 4, 8, and 12 and compared. Adverse events were also evaluated. Results Improvements in weekly UUI episodes were similar for the 790 women who received extended-release formulations of oxybutynin (n=391) or tolterodine (n=399). Oxybutynin was significantly more effective than tolterodine in reducing micturition frequency ( P =.003), and 23.0% of women taking oxybutynin reported no episodes of urinary incontinence compared with 16.8% of women taking tolterodine ( P =.03). Dry mouth, usually mild, was more common with oxybutynin ( P =.02). Adverse events were generally mild and occurred at low rates, with both groups having similar discontinuation of treatment due to adverse events. Conclusions Reductions in weekly UUI and total incontinence episodes were similar with extended-release formulations of oxybutynin and tolterodine. In the oxybutynin group, micturition frequency was significantly lower, and the percentage of women reporting no urinary incontinence episodes was significantly higher compared with the tolterodine group. Dry mouth was more common with oxybutynin, but tolerability was otherwise comparable, including adverse events involving the central nervous system.