Elsevier

Urology

Volume 57, Issue 3, March 2001, Pages 414-421
Urology

Adult urology
Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder1,

https://doi.org/10.1016/S0090-4295(00)01113-4Get rights and content

Abstract

Objectives. To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder.

Methods. This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. 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 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (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 comparable 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. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.

Section snippets

Material and methods

This multinational, randomized, double-blind, placebo-controlled study was conducted in 167 centers in Australasia (n = 4), Europe (n = 89), and North America (n = 74). The study was conducted in accordance with the Good Clinical Practice Guidelines and the Declaration of Helsinki. The ethics committees approved the study protocol, and all patients gave written informed consent before the start of the study.

Results

A total of 1529 patients with overactive bladder were randomized into the study. The study population was representative of an expected population of patients with overactive bladder. Thus, most patients (81%) were women and approximately 50% of patients in each treatment group had received previous treatment for overactive bladder, 41% of whom had experienced poor results. The treatment groups were also well matched with regard to demographic and baseline disease characteristics (Table I).

All

Comment

Overactive bladder is a chronic condition that requires long-term treatment to maintain symptom relief. Numerous large, multinational, multicenter studies have confirmed the efficacy of tolterodine IR in treating the symptoms of overactive bladder.8, 9, 10, 11, 12 However, a once-daily administration may be viewed as potentially more convenient by patients, and this could lead to increased compliance.13 This study was the first large, multinational, multicenter, placebo-controlled investigation

Conclusions

At a dosage of 4 mg once daily, the ER formulation of tolterodine produces significant improvements in the symptoms of overactive bladder compared with placebo. The ER formulation was more effective in reducing the incontinence episodes and was better tolerated than the IR formulation, with a lower frequency of dry mouth at all severity levels. The advent of this new, once-daily formulation of tolterodine, combining highly effective relief of symptoms with minimal side effects and maximal

References (24)

  • L Nilvebrant

    The mechanism of action of tolterodine

    Rev Contemp Pharmacother

    (2000)
  • M.M.S Stahl et al.

    Urodynamic and other effects of tolterodinea novel antimuscarinic drug for the treatment of detrusor overactivity

    Neurourol Urodyn

    (1995)
  • Cited by (419)

    • Medical Treatment of Overactive Bladder

      2022, Urologic Clinics of North America
    • Anticholinergic medication: Related dry mouth and effects on the salivary glands

      2021, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
    View all citing articles on Scopus

    This study was sponsored by Pharmacia Corporation.

    1

    A complete list of the members of the Tolterodine Study Group is provided in the Appendix.

    View full text