Tolterodine once-daily: Superior efficacy and tolerability in the treatment of the overactive bladder

Objectives. To evaluate the efficacy and tolerability of a new extended-rel ease (ER), once-daily, capsule formulation of tolterodine, relative to plac ebo and the existing immediate-release (IR), twice-daily, tablet formulatio n, for treatment of the overactive bladder. Methods, This was a double-blind, multicenter, randomized, placebo-controll ed trial. One thousand five hundred twenty-nine patients (81% women) with u rinary frequency (eight or more micturitions every 24 hours) and urge incon tinence (five or more episodes per week) were randomized to oral therapy wi th tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice dail y (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at th e end of the treatment period on the basis of the micturition diary variabl es. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals . Results. Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 m g twice daily (P = 0.0005) both significantly reduced the mean number of ur ge incontinence episodes per week compared with placebo. The median reducti on in these episodes as a percentage of the baseline values was 71% for tol terodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulatio n was 18% more effective than the IR formulation (P < 0.05). Treatment with both formulations of tolterodine was also associated with statistically si gnificant improvements in all other micturition diary variables compared wi th placebo. For both formulations, the mean decreases in micturition freque ncy (P < 0.0079) and pad usage (P < 0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P < 0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comp arable for the two active groups and the placebo group. No safety concerns were noted. Conclusions. Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodin e ER demonstrated an improved efficacy for reducing urge incontinence episo des and a lower frequency of dry mouth compared with the existing IR twice- daily formulation. UROLOGY 57: 414-421, 2001, (C) 2001, Elsevier Science In c.