Tolterodine: A Review of its Use in the Treatment of Overactive Bladder


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Abstract

Tolterodine is a competitive muscarinic receptor antagonist that shows in vivo selectivity for the bladder over the salivary glands compared with oxybutinin.Results of randomised double-blind placebo-controlled studies indicate that tolterodine 4 mg/day (administered as immediate-release tablets 2mg twice daily or extended-release capsules 4mg daily) is superior to placebo in improving micturition diary variables in patients with overactive bladder. Moreover, tolterodine 2mg twice daily is as effective as oxybutynin 5mg 3 times daily. Maximum treatment effects with both drugs occurred after 5 to 8 weeks of treatment and improvements were maintained during long term treatment for up to 24 months.In a pooled analysis of four 12-week studies, equivalent and significant reductions in micturition frequency (−2.3 and −2.0 vs −1.4, p < 0.001) and the incidence of urge incontinence episodes (−1.6 and −1.8 vs −1.1, p < 0.05) were reported for tolterodine 2mg twice daily and oxybutynin 5mg 3 times daily compared with placebo. Functional bladder capacity was also significantly increased.Improvements in patient perceptions of their urgency symptoms and of problems caused by their bladder condition were significantly greater during treatment with tolterodine than with placebo.Tolterodine was generally well tolerated in clinical trials of up to 24 months' duration. Dry mouth was the most frequent adverse event. The incidence (40 vs 78%, p < 0.001) and intensity of this event was lower with tolterodine 2mg twice daily than oxybutynin 5mg 3 times daily. Additionally, a 23% lower incidence of dry mouth was reported with once daily extended-release tolterodine capsules than with twice daily immediate-release tablets (p < 0.02). The incidence of adverse CNS events with tolterodine was low and similar to that of placebo. Tolterodine was well tolerated in elderly patients and no serious tolerability concerns were identified.ConclusionsTolterodine is the first antimuscarinic agent to be specifically developed for the treatment of overactive bladder. The functional selectivity of tolterodine for the bladder translates into good efficacy and tolerability in patients, including the elderly, with overactive bladder. Tolterodine is as effective as oxybutynin in improving micturition diary variables but is associated with a significantly lower incidence and intensity of dry mouth. This favourable tolerability profile, together with sustained clinical efficacy during long term treatment, places tolterodine as a valuable treatment for the symptoms of overactive bladder.

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