tolterodine-tartrate and Urinary-Incontinence

To present a systematic review assessing the efficacy and safety of mirabegron for overactive bladder (OAB).. A literature search was performed using the Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded. The literature reviewed included meta-analyses, randomized and nonrandomized prospective studies. We utilized mean difference (MD) to measure the mean number of incontinence episodes and the mean number of micturitions, and OAB questionnaire (OAB-q) and odds ratio (OR) to measure adverse events rates. We used the Cochrane Collaboration's Review Manager 5.1 software for statistical analysis.. We identified six publications that strictly met our eligibility criteria. Meta-analysis of extractable data showed that mirabegron was more effective than placebo in treating OAB despite different drug dosages in the efficacy end points: mean number of incontinence episodes per 24 h (MD -0.54; 95% CI -0.63, -0.45; p = 0.001), mean number of micturitions per 24 h (MD -0.55; 95% CI -0.63, -0.47; p = 0.001), OAB-q (MD -4.49; 95% CI -6.27, -2.71; p = 0.001) and adverse events (OR 0.99; 95% CI 0.83, 1.19; p = 0.92). When compared to tolterodine, mirabegron was more effective in terms of mean number of incontinence episodes per 24 h (MD -0.25; 95% CI -0.43, -0.06; p = 0.009). However, there were no differences between mirabegron and tolterodine in mean number of micturitions per 24 h (MD -0.17; 95% CI -0.35, 0.01; p = 0.07) and OAB-q (MD -1.09; 95% CI -2.51, 0.33; p = 0.13). Mirabegron also had a lower adverse reaction rate (OR 0.9; 95% CI 0.8, 1.0; p = 0.04).. In this diverse population, mirabegron was an effective and safe pharmacologic therapy for OAB.

Topics: Acetanilides; Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Odds Ratio; Phenylpropanolamine; Prospective Studies; Research Design; Software; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To examine pooled efficacy data from three, large phase III studies comparing mirabegron (50 and 100 mg) with placebo, and pooled safety data including additional mirabegron 25 mg and tolterodine extended release (ER) 4 mg results.. This prespecified pooled analysis of three randomised, double-blind, placebo-controlled, 12-week studies, evaluated efficacy and safety of once-daily mirabegron 25 mg (safety analysis), 50 or 100 mg (efficacy and safety analyses) and tolterodine ER 4 mg (safety analysis) for the treatment of symptoms of overactive bladder (OAB). Co-primary efficacy measures were change from baseline to Final Visit in the mean number of incontinence episodes/24 h and mean number of micturitions/24 h. Key secondary efficacy end-points included mean number of urgency episodes/24 h and mean volume voided/micturitions, while other end-points included patient-reported outcomes according to the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) and responder analyses [dry rate (posttreatment), ≥ 50% reduction in incontinence episodes/24 h, ≤ 8 micturitions/24 h (post hoc analysis)]. The safety analysis included adverse event (AE) reporting, laboratory assessments, ECG, postvoid residual volume and vital signs (blood pressure, pulse rate).. Mirabegron (50 and 100 mg once daily) demonstrated statistically significant improvements compared with placebo for the co-primary end-points, key secondary efficacy variables, TS-VAS and responder analyses (all comparisons p < 0.05). Mirabegron is well tolerated and demonstrates a good safety profile. The most common AEs (≥ 3%) included hypertension, nasopharyngitis and urinary tract infection (UTI); the incidence of hypertensive events and UTIs decreased with increasing dose. For mirabegron, the incidence of the bothersome antimuscarinic AE, dry mouth, was at placebo level and of a lesser magnitude than tolterodine.. The efficacy and safety of mirabegron are demonstrated in this large pooled clinical trial dataset in patients with OAB.

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents; Young Adult

Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments.. To compare the effects of different anticholinergic drugs for overactive bladder symptoms.. We searched the Cochrane Incontinence Group Specialised Trials Register (searched 8 March 2011) and reference lists of relevant articles.. Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug.. Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook.. Eighty six trials, 70 parallel and 16 cross-over designs were included (31,249 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analyses. Twenty nine collected quality of life data (the primary outcome measure) using validated measures, but only fifteen reported useable data.Tolterodine versus oxybutynin: There were no statistically significant differences for quality of life, patient reported cure or improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events with tolterodine (Risk Ratio (RR) 0.52, 95% confidence interval (CI) 0.40 to 0.66, data from eight trials), and less risk of dry mouth (RR 0.65, 95% CI 0.60 to 0.71, data from ten trials).Solifenacin versus tolterodine: There were statistically significant differences for quality of life (standardised mean difference (SMD) -0.12, 95% CI -0.23 to -0.01, data from three trials), patient reported cure/improvement (RR 1.25, 95% CI 1.13 to 1.39, data from two trials), leakage episodes in 24 hours (weighted mean difference (WMD) -0.30, 95% CI -0.53 to -0.08, data from four studies) and urgency episodes in 24 hours (WMD -0.43, 95% CI -0.74 to -0.13, data from four trials), all favouring solifenacin. There was no difference in withdrawals due to adverse events and dry mouth, but after sensitivity analysis the dry mouth (RR 0.69, 95% CI 0.51 to 0.94) was statistically significantly lower with solifenacin when compared to Immediate Release (IR) tolterodine.Fesoterodine versus extended release tolterodine: Three trials contributed to the meta analyses. There were statistically significant differences for quality of life (SMD -0.20, 95% CI -0.27 to -0.14), patient reported cure/improvement (RR 1.11, 95% CI 1.06 to 1.16), leakage episodes (WMD -0.19, 95% CI -0.30 to -0.09), frequency (WMD -0.27, 95% CI -0.47 to -0.06) and urgency episodes (WMD -0.44, 95% CI -0.72 to -0.16) in 24 hours, all favouring fesoterodine, but those taking fesoterodine had higher risk of withdrawal due to adverse events (RR 1.45, 95% CI 1.07 to 1.98) and higher risk of dry mouth (RR 1.80, 95% CI 1.58 to 2.05) at 12 weeks.Different doses of tolterodine: The standard recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effects of 1 mg, 2 mg and 4 mg doses were similar for leakage. Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective, with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth.Between solifenacin and immediate release tolterodine, solifenacin might be preferred for better efficacy and less risk of dry mouth. Solifenacin 5 mg once daily is the usual starting dose, this could be increased to 10 mg once daily for better efficacy but with increased risk of dry mouth.Between fesoterodine and extended release tolterodine, fesoterodine might be preferred for superior efficacy but has higher risk of withdrawal due to adverse events and higher risk of dry mouth.There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Topics: Adult; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Phenylpropanolamine; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

Urinary incontinence (UI) in women adversely affects quality of life.. To conduct a systematic literature review of drugs for urgency UI in women.. MEDLINE, the Cochrane Central Register of Controlled Trials, SCIRUS, and Google Scholar were searched for articles published from 1966 to November 2011.. Randomized, controlled trials (RCTs) reported in English.. Rates of outcomes and risk of bias were extracted by using a standardized form to pool absolute risk differences and calculate the number of attributable events per 1000 patients treated, with 95% CIs.. 94 RCTs were eligible. Pooled analyses showed that among drugs for urgency UI, per 1000 treated women, continence was restored in 130 with fesoterodine (CI, 58 to 202), 85 with tolterodine (CI, 40 to 129), 114 with oxybutynin (CI, 64 to 163), 107 with solifenacin (CI, 58 to 156), and 114 with trospium (CI, 83 to 144). Rates of treatment discontinuation due to adverse effects were 31 per 1000 treated with fesoterodine (CI, 10 to 56), 63 with oxybutynin (CI, 12 to 127), 18 with trospium (CI, 4 to 33), and 13 with solifenacin (CI, 1 to 26). The studies' inconsistent definitions of reduction in UI and quality of life hampered synthesis of evidence.. Evidence for quality-of-life improvements and comparative effectiveness with drugs was limited, and evidence for the effects of race, baseline severity of UI, and comorbid conditions on treatment success was insufficient.. Overall, drugs for urgency UI showed similar small benefit. Therapeutic choices should consider the harms profile. Evidence for long-term adherence and safety of treatments is lacking.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Comparative Effectiveness Research; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quality of Life; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs).. The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse events, pharmacokinetics, tolerability" in combination with "darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.". Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Chronic Disease; Cresols; Drug Combinations; Female; Humans; Imidazoles; Mandelic Acids; Muscarinic Antagonists; Nocturia; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

The epidemiology and treatment of mixed incontinence has received relatively little attention. However, mixed incontinence--defined as the combination of stress and urge incontinence accounts for approximately 33% of all cases of incontinence in women. The condition often responds poorly to treatment, either pharmacologic or surgical. Potential pharmacologic approaches for mixed incontinence include antimuscarinic agents, estrogen replacement therapy (for postmenopausal women), and dopamine, serotonin, or norepinephrine reuptake inhibitors. In a large-scale, multinational, placebo-controlled, clinical trial, the antimuscarinic agent tolterodine significantly reduced incontinence episodes in women with mixed symptoms. The benefits of tolterodine continued to increase during the 8 weeks of the trial and extended to additional end points, including frequency, urgency, and urge incontinence. A limited number of studies have examined the use of estrogen for mixed incontinence and have produced conflicting results. Duloxetine oxalate, a combined serotonin/norepinephrine reuptake inhibitor, has shown great promise in animal studies, as well as in phase 2 and 3 clinical trials. This agent is the first to demonstrate efficacy as a sole therapy for stress incontinence and has exhibited favorable effects on bladder capacity, suggesting possible benefits in mixed incontinence. Only five studies (two of which were conducted during the 1980s) have specifically examined the use of surgery for the treatment of mixed incontinence; the cure rates reported have varied. The current body of information supports use of an antimuscarinic agent as initial therapy for mixed incontinence, although long-term trials are needed to shed more light on the duration of benefit.

Topics: Adrenergic Uptake Inhibitors; Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Duloxetine Hydrochloride; Estrogens; Female; Humans; Muscarinic Antagonists; Phenylpropanolamine; Selective Serotonin Reuptake Inhibitors; Thiophenes; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urinary Incontinence, Urge

Overactive bladder (OAB) is a common problem. Affected individuals suffer decreased quality of life and productivity. The mainstay of pharmacological treatment of OAB is antimuscarinic agents. Tolterodine was the first antimuscarinic drug designed specifically for treating OAB. Compared with the immediate-release (IR) drug, once-daily tolterodine extended-release (ER) releases the drug in a steady but constant manner lowering peak and trough drug levels. This translates to more constant serum concentrations and theoretically better patient tolerability. The dry mouth rate for the ER formulation has been reported to be lower than for the IR formulation. Recent literature strongly supports the efficacy and safety of tolterodine ER in carefully selected older men with OAB symptoms. Tolterodine ER is well tolerated and withdrawal rates are similar to those in placebo. Fesoterodine is a new antimuscarinic that shares the same active metabolite as tolterodine and may provide less pharmacokinetic variability. We support tolterodine ER for treating for OAB. It has proven efficacy and tolerability.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Drug Administration Schedule; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Urinary incontinence in women is a common problem that adversely affects quality of life.. To synthesize evidence of management of urinary incontinence in women.. MEDLINE, CINAHL, and the Cochrane Library.. 96 randomized, controlled trials (RCTs) and 3 systematic reviews published in English from 1990 through May 2007.. Using standardized protocols, reviewers abstracted cases of continence, improvement of urinary incontinence, and prevalence of urinary incontinence to calculate risk difference.. Compared with regular care, pelvic floor muscle training plus bladder training resolved urinary incontinence (pooled risk difference, 0.13 [95% CI, 0.07 to 0.20]). Pelvic floor muscle training alone resolved or improved urinary incontinence compared with regular care, although the effect size was inconsistent across studies. Different injectable bulking agents and medical devices were associated with similar continence and improvement rates. Electrical stimulation failed to resolve urinary incontinence. Oral hormone administration increased rates of urinary incontinence compared with placebo in most RCTs (1243 women). Transdermal or vaginal estrogen resulted in inconsistent improvement of urinary incontinence. Adrenergic drugs did not resolve or improve urinary incontinence. Oxybutynin or tolterodine resolved urinary incontinence compared with placebo (pooled risk difference, 0.18 [CI, 0.13 to 0.22]). Duloxetine compared with placebo improved (pooled risk difference, 0.11 [CI, 0.07 to 0.14]) but did not resolve urinary incontinence, with no significant dose-response association.. Inconsistent measurements of outcomes limited the findings. Predictors of better effect have not been identified in RCTs.. Moderate levels of evidence suggest that pelvic floor muscle training and bladder training resolved urinary incontinence in women. Anticholinergic drugs resolved urinary incontinence, with similar effects from oxybutynin or tolterodine. Duloxetine improved but did not resolve urinary incontinence. The effects of electrostimulation, medical devices, injectable bulking agents, and local estrogen therapy were inconsistent.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Collagen; Cresols; Duloxetine Hydrochloride; Electric Stimulation Therapy; Estrogen Replacement Therapy; Exercise Therapy; Female; Humans; Magnetics; Mandelic Acids; Pelvic Floor; Pessaries; Phenylpropanolamine; Randomized Controlled Trials as Topic; Thiophenes; Tolterodine Tartrate; Urinary Incontinence

Mixed incontinence remains a complex clinical problem for urogynaecologists and generalists alike, as research for new treatments and interventions tend to focus on single-symptom groups. Those with mixed symptoms form a diverse group, which is difficult to study precisely. Recent studies, however, have aimed to classify the subgroups within this heterogeneous group so that the response to treatment can be determined with greater accuracy. This review aims to evaluate these advances and place the research in a clinical context.. The main developments have occurred with the acknowledgement of the large number of patients with these symptoms, the assessment of patients and attempts to classify symptom predominant types. Responses following pharmacological and surgical treatment have also improved.. There is greater awareness of the prevalence of mixed urinary incontinence, which has a large impact on the quality of life of women, irrespective of their desire to seek medical help. Tools are available to identify different subgroups within the sphere of mixed urinary incontinence, and, once accurately assessed, patients can expect good outcomes from treatment. Further collaboration between units will lead to more consistent information being published.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Benzhydryl Compounds; Combined Modality Therapy; Cresols; Duloxetine Hydrochloride; Female; Humans; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Severity of Illness Index; Thiophenes; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urodynamics; Urologic Surgical Procedures

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Overactive bladder (OAB) is a chronic syndrome with debilitating symptoms that negatively affect health-related quality of life. Although anticholinergic agents have been first-line treatment for OAB for many years, the efficacious pharmacologic management of this condition has been compromised by concerns regarding tolerability. Anticholinergic agents prevent involuntary contractions of the bladder detrusor muscle by preventing acetylcholine from binding to the M2 and M3 muscarinic receptor subtypes. Anticholinergics are not tissue specific, and their use for treatment of OAB has been associated with side effects such as dry mouth, constipation, and blurred vision. Recent studies with extended-release formulations and newly developed receptor subtype-specific anticholinergic agents demonstrate that side effects are typically mild to moderate and generally tolerable, seldom leading to patient withdrawal. By incorporating patient-initiated dose adjustment into the protocol, the primary care physician can effectively manage adverse events associated with OAB without compromising efficacy. Recent dose-adjustment data with extended-release oxybutynin suggest that, given some control in the process, patients are willing to tolerate certain side effects in exchange for symptom relief.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Overactive bladder is a common and distressing problem. Standard therapy is directed towards modifying the detrusor motor sensitivity and response via anticholinergic medication. Currently available medications are reviewed and alternative targets for treatment are presented.

Topics: Acetylcholine; Amines; Animals; Anticonvulsants; Benzhydryl Compounds; Cresols; Cyclohexanecarboxylic Acids; Drug Evaluation, Preclinical; Gabapentin; gamma-Aminobutyric Acid; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Product Surveillance, Postmarketing; Quinuclidines; Randomized Controlled Trials as Topic; Receptor, Muscarinic M3; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

Overactive bladder is a syndrome characterised by urinary urgency, with or without urge incontinence, and usually with frequency and nocturia. It affects millions of people of all ages worldwide and causes significant morbidity, especially in terms of health-related quality of life. It poses a huge economic burden on health resources. Managing such patients involves a thorough history, physical examination and the use of pertinent investigations before the initiation of treatment. Therapy consists of lifestyle changes, bladder training, anticholinergics, second-line agents such as resiniferatoxin instillation or botulinum toxin injections into the bladder in refractory cases and, finally, in intractable cases, surgery. In the first part of this review of pharmacotherapy for the treatment of this condition, the focus is on the pathophysiological factors potentially involved in overactive bladder and covers the wide range of currently available first-line anticholinergic agents. Treatment algorithms are suggested on the basis of current literature.

Topics: Administration, Cutaneous; Administration, Intravesical; Administration, Oral; Algorithms; Animals; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Models, Animal; Phenylpropanolamine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To determine if there is a significant difference in outcomes of clinical trials funded by industry or not of antimuscarinic medications used to treat overactive bladder (OAB) symptoms and detrusor overactivity (DOA).. A Medline search was conducted from January 1966 to June 2003 to identify human clinical trials of oxybutynin and tolterodine published in English. Randomized controlled trials on subjects aged > or = 16 years who were being treated with oxybutynin or tolterodine for OAB symptoms or DOA; 24 studies were identified. The endpoints assessed were OAB symptoms or changes in uninhibited detrusor contractions on cystometrography. The outcome variables were dichotomized as 'improvement' or 'no improvement'. Odds ratios and 95% confidence intervals were calculated for each study based on data derived or extracted from tables and figures.. Meta-analysis showed no significant difference in the outcomes trails funded by industry or not. Trials were then reviewed to determine their adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines for randomized trials.. Clinical trials are important for clinicians when selecting medical therapies. In this analysis we found no difference in outcomes when comparing studies funded by industry or not for tolterodine and oxybutynin. The quality of all trials would be improved by close adherence to the CONSORT guidelines for randomized clinical trials.

Topics: Benzhydryl Compounds; Cresols; Drug Industry; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Research Support as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Primary care physicians must initiate a discussion of overactive bladder and urinary incontinence with their patients who are at risk. A stepwise approach to evaluation and diagnosis and the use of systematic evaluation and treatment algorithms suitable to the primary care setting will improve identification and effective management of the incontinent patient.

Topics: Algorithms; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Imipramine; Mandelic Acids; Phenylpropanolamine; Primary Health Care; Tolterodine Tartrate; Urinary Incontinence; Urinary Incontinence, Stress

Overactive bladder (OAB) is a prevalent condition. Numerous clinical trials have demonstrated the efficacy and safety of immediate release tolterodine in the treatment of OAB in different patient populations. This review details the characteristics, clinical efficacy and safety of extended release (ER) tolterodine. This formulation yields a flatter serum concentration profile and provides clinically meaningful symptom improvement as early as week 1 of treatment. Tolterodine ER is effective in diverse patient populations with varying levels of symptom severity, and efficacy is maintained with long-term treatment. Tolterodine is an effective, safe, and convenient treatment option for long-term relief of OAB symptoms.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Urinary incontinence is caused by an overactive bladder, leading to symptoms of urgency, frequency, and incontinence. Urge incontinence occurs predominantly in women as they age.. This article reviews the current primary literature concerning the efficacy and tolerability of the anticholinergic agent trospium chloride (TCl) in the treatment of overactive bladder with symptoms of urge incontinence, urgency, and frequency. The pharmacokinetics of TCl are also reviewed.. Pertinent articles in English were identified through a search of MEDLINE (1966-present), EMBASE Drugs & Pharmacology (1980-third quarter 2004), Current Contents/Clinical Medicine (week 42, 2003-week 41, 2004), Cochrane Database of Systematic Reviews, MICROMEDEX Healthcare Series, and International Pharmaceutical Abstracts (1970-present). The search terms were overactive bladder, urinary incontinence, trospium, randomized controlled clinical trial, oxybutynin, tolterodine, scopolamine, imipramine, desipramine, and propantheline.. TCl, a quaternary amine, exhibits high solubility in water but low oral bioavailability (9.6%) and poor central nervous system penetration. Approximately 80% of the absorbed fraction is renally eliminated as unchanged drug via active tubular secretion, with approximately 15% hepatically metabolized into a spiroalcohol and hydrolysis/oxidation products. In 3 placebo-controlled studies, patients who received TCl had an increase in maximum bladder filling capacity and bladder compliance, with a reduction in maximum cystometric capacity (P < 0.005); however, only 1 of these studies showed an increase in bladder compliance, with reductions in maximum detrusor pressure (P < 0.001), number of voids/d (P < or = 0.001), and incontinence episodes/d (P < or = 0.001). In another placebo-controlled study, TCl reduced the number of voids/d and incontinence episodes/d (both, P < or = 0.001). In 2 double-blind studies, TCl and oxybutynin were similarly effective in significantly increasing maximum cystometric capacity and bladder compliance, and in significantly reducing maximum detrusor pressure compared with baseline (all, P < 0.001); there were no significant differences between the 2 treatments at end point. In a third double-blind study comparing TCl and tolterodine with placebo, only TCl significantly reduced the frequency of micturitions/d (P = 0.01). Commonly reported adverse effects in patients receiving TCl included dry mouth, constipation, and headache.. In the 7 studies reviewed, TCl was effective and well tolerated in patients with urge incontinence caused by idiopathic detrusor muscle overactivity or neurogenic detrusor overactivity resulting from spinal cord injury. However, this agent was associated with anticholinergic adverse effects similar to those of other anticholinergic agents; careful monitoring of tolerability is required.

Topics: Aging; Area Under Curve; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Female; Humans; Liver Failure; Male; Mandelic Acids; Metabolic Clearance Rate; Nortropanes; Phenylpropanolamine; Randomized Controlled Trials as Topic; Renal Insufficiency; Tolterodine Tartrate; Urinary Incontinence

Topics: Aged; Behavior Therapy; Benzhydryl Compounds; Cresols; Exercise Therapy; Female; Humans; Male; Mandelic Acids; Mass Screening; Medical History Taking; Middle Aged; Muscarinic Antagonists; Nurse Practitioners; Nurse's Role; Nursing Assessment; Pelvic Floor; Phenylpropanolamine; Physical Examination; Prevalence; Risk Factors; Tolterodine Tartrate; United States; Urinalysis; Urinary Incontinence; Urodynamics

Around 16% to 45% of adults have overactive bladder symptoms (urgency with frequency and/or urge incontinence - 'overactive bladder syndrome'). Anticholinergic drugs are common treatments.. To compare the effects of different anticholinergic drugs for overactive bladder symptoms.. We searched the Cochrane Incontinence Group specialised trials register (searched 17 January 2002) and reference lists of relevant articles. A search for full publications of abstracts identified in January 2002 was completed in July 2003.. Randomised trials in adults with overactive bladder symptoms or detrusor overactivity that compared one anticholinergic drug with another, or two doses of the same drug.. Two authors independently assessed eligibility, trial quality and extracted data. Data were processed as described in the Cochrane Reviewers' Handbook.. Forty nine trials, 39 parallel and 10 cross-over designs were included (11,332 adults). Most trials were described as double-blind, but were variable in other aspects of quality. Crossover studies did not present data in a way that could be included in the meta-analysis.Four trials collected quality of life data (the primary outcome measure) using validated measures; none reported useable data. Oxybutynin versus tolterodine: There were no statistically significant differences for patient perceive improvement, leakage episodes or voids in 24 hours, but fewer withdrawals due to adverse events (RR 0.57, 95% CI 0.43 to 0.75), and less risk of dry mouth (RR 0.60, 95% CI 0.54 to 0.66), with tolterodine. Different doses tolterodine: The usual recommended starting dose (2 mg twice daily) was compared with two lower (0.5 mg and 1 mg twice daily), and one higher dose (4 mg twice daily). The effect of 1 mg, 2 mg and 4 mg doses was similar for leakage episodes and micturitions in 24 hours, with greater risk of dry mouth with 2 and 4 mg doses.Extended versus immediate release preparations of oxybutynin and/or tolterodine: There were no statistically significant differences for cure/improvement, leakage episodes or micturitions in 24 hours, or withdrawals due to adverse events, but there were few data. Overall, extended release preparations had less risk of dry mouth. One extended release preparation versus another: There was less risk of dry mouth with oral extended release tolterodine than oxybutynin (RR 0.75, 95% CI 0.59 to 0.95), but no difference between transdermal oxybutynin and oral extended release tolterodine although some people withdrew due to skin reaction at the trandermal patch site.. Where the prescribing choice is between oral immediate release oxybutynin or tolterodine, tolterodine might be preferred for reduced risk of dry mouth. With tolterodine, 2 mg twice daily is the usual starting dose, but a 1 mg twice daily dose might be equally effective with less risk of dry mouth. If extended release preparations of oxybutynin or tolterodine are available, these might be preferred to immediate release preparations because there is less risk of dry mouth. There is little or no evidence available about quality of life, costs, or long-term outcome in these studies. There were insufficient data from trials of other anticholinergic drugs to draw any conclusions.

Topics: Adult; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Humans; Mandelic Acids; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence

Overactive bladder is a common condition, with recent findings estimating the prevalence in adults at about 15%. Symptoms, including urinary urgency, high voiding frequency and urge incontinence, have been shown to decrease patients' quality of life. Given its high prevalence, the economic burden of overactive bladder is also substantial, with a recent estimate placing the annual cost in the US at 9.1 billion US dollars (year 2000 values). The objective of this review is to provide a critical appraisal of published economic evaluations of pharmacological and non-pharmacological treatments for overactive bladder. Published economic evaluations of treatments for overactive bladder have focused entirely on pharmacological treatments -- mainly on the two most commonly used drugs, oxybutynin and tolterodine, each of which is available in immediate- and extended-release formulations. Ten economic evaluations (more than half are cost-effectiveness studies) have been published. Modelling with decision trees or Markov models has been the predominant method. Evaluations comparing drug therapy with no treatment have concluded that drug therapy is cost effective. Analyses comparing the formulations of oxybutynin and tolterodine have produced highly inconsistent results, largely due to the sources of data employed for effectiveness and treatment discontinuation rates. There are no evaluations of drugs relative to non-pharmacological treatment, and there are other significant gaps in the economic evaluations of treatment to date. These include gaps resulting from a lack of reliable data on the performance of these drugs in real-world settings, particularly data on long-term persistence with treatment. A more definitive pharmacoeconomic comparison of oxybutynin and tolterodine formulations, incorporating all available clinical data, and other treatment options would help direct treatment.

Topics: Benzhydryl Compounds; Cost of Illness; Cresols; Female; Humans; Male; Mandelic Acids; Markov Chains; Middle Aged; Models, Economic; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Tolterodine Tartrate; United States; Urinary Incontinence

The combination of an alpha1-blocker with an anticholinergic is a new and promising therapeutic approach for bladder outlet obstruction and detrusor overactivity. Both placebo-controlled and comparative studies have demonstrated that the addition of an anticholinergic in the conventional treatment of patients with bladder outlet obstruction is safe, as the likelihood of acute urinary retention is low. Although the pathophysiology of detrusor overactivity is unknown and most probably multifactorial, it is not expected that the voiding phase is influenced by regular doses of anticholinergics, although high doses may affect detrusor contraction. However, safety issues must be studied further. The combination of tamsulosin with propiverine or tolterodine, and of doxasosin with tolterodine has been shown to cause a significant improvement of lower urinary tract symptoms when compared with alpha1-blocker monotherapy. Indisputably, the existing literature provides clear evidence that the combination of an alpha1-blocker with an anticholinergic extends physicians ability to manage lower urinary tract symptoms caused by bladder outlet obstruction and overactive bladder syndrome.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Benzhydryl Compounds; Benzilates; Cholinergic Antagonists; Cresols; Doxazosin; Drug Therapy, Combination; Humans; Male; Phenylpropanolamine; Prostatic Hyperplasia; Randomized Controlled Trials as Topic; Sulfonamides; Tamsulosin; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urinary Incontinence; Urodynamics; Urologic Diseases

Overactive bladder is associated with symptoms of urgency, with or without urge incontinence, usually with daytime frequency and nocturia in the absence of local pathological factors. Muscarinic receptor antagonists (antimuscarinics) are the first-line pharmacotherapy. Tolterodine, a competitive, nonselective antimuscarinic specifically developed for the treatment of overactive bladder, demonstrated tissue selectivity for the bladder over the parotid gland in an animal model. As of March 5, 2003, the immediate-release (IR) formulation had been approved in 72 countries and the extended-release (ER) formulation had been approved in 28 countries, and tolterodine had been administered to 5 million patients. This review evaluates the benefit-risk profile of tolterodine in the treatment of adults with overactive bladder, summarising clinical trial and postmarketing surveillance data. Tolterodine has been found to significantly reduce micturition frequency, urgency perception and the number of episodes of urge incontinence and increase the volume voided per micturition. Dry mouth, an antimuscarinic class effect, is the most commonly reported adverse effect but is mostly mild to moderate in severity. Serious adverse effects are reported infrequently. Based on summary and review of postmarketing surveillance and clinical trial safety data received by the market authorization holder and contained in the Periodic Safety Update Reports for tolterodine, several monitored serious events of the gastrointestinal tract (e.g. ileus or haemorrhage), nervous system (e.g. syncope, convulsions and memory disorders) and cardiovascular system (e.g. ventricular arrhythmia, atrial fibrillation, palpitations, bradycardia, transient ischaemic attacks and hypertension) were not considered related to tolterodine. QT or corrected QT (QTc) prolongation was not observed in any of the five cases of verified ventricular arrhythmia in patients administered tolterodine; there is insufficient evidence to indicate that tolterodine causes ventricular arrhythmia or extrasystoles or any specific type of cardiac rhythm abnormality. The safety profile of tolterodine is similar in patients aged > or =65 years and in younger adults. Clinically relevant drug interactions are limited to cytochrome P450 3A4 inhibitors, such as ketoconazole, and co-administration with such agents warrants a tolterodine dosage decrease. In addition, tolterodine IR 2mg twice daily is similar in efficacy to oxybutynin IR 5m

Topics: Adult; Aged; Benzhydryl Compounds; Constipation; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Risk Assessment; Tolterodine Tartrate; Urinary Incontinence

Trospium chloride is an orally active, quaternary ammonium compound with antimuscarinic activity. It binds specifically and with high affinity to muscarinic receptors M(1), M(2) and M(3), but not nicotinic, cholinergic receptors. It is hydrophilic and does not cross the normal blood-brain barrier in significant amounts and, therefore, has minimal central anticholinergic activity. Peak plasma trospium chloride concentrations are attained approximately 5-6 hours after oral administration, which should occur before meals as concurrent food ingestion significantly reduces trospium bioavailability. Trospium chloride undergoes negligible metabolism by the hepatic cytochrome P450 system; few metabolic drug interactions are known. While trospium chloride dosage adjustments based on age or sex appear unwarranted, such adjustments may be needed in patients with severe renal impairment. Direct comparative studies in patients with overactive bladder indicate that trospium chloride is at least as effective as oxybutynin and tolterodine. Placebo-controlled studies have also confirmed the efficacy of trospium chloride in terms of improved urodynamic parameters; small-scale, noncomparative studies have documented significant trospium chloride-induced improvements in patients with reflex neurogenic bladder, postoperative bladder irritation and radiation-induced cystitis; and observational studies including >10,000 patients have also revealed favourable findings for trospium chloride, including a marked decrease in incontinence episodes and substantial improvement in health-related quality of life. Trospium chloride is generally well tolerated, and significantly more so than immediate-release oxybutynin. The most frequent adverse events, occurring in >1% of trospium chloride-treated patients, are dry mouth, dyspepsia, constipation, abdominal pain and nausea. Available for many years in several countries outside North America, trospium chloride is likely to develop an important role in the management of overactive bladder following its approval in the US on 28 May 2004.

Topics: Benzhydryl Compounds; Benzilates; Biological Availability; Cresols; Female; Half-Life; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Randomized Controlled Trials as Topic; Receptors, Muscarinic; Tissue Distribution; Tolterodine Tartrate; Urinary Incontinence

Drug therapy for overactive bladder (OAB) most commonly includes antimuscarinic agents, which work by relaxing bladder smooth muscle through inhibition of acetylcholine receptors in the bladder. The major adverse effects with existing antimuscarinic agents are anticholinergic in nature (e.g., dry mouth, constipation, blurred vision). Oxybutynin and tolterodine have been used for several years for treatment of OAB; both are available in immediate- and extended-release formulations. Fewer or less severe adverse effects are reported with the extended- versus the immediate-release formulations, with little or no difference in efficacy. Oxybutynin is also available as a transdermal patch. Trospium, which was recently approved for use in the United States, has efficacy and an incidence of dry mouth similar to existing agents but does not cross the blood-brain barrier. It requires twice-daily dosing. Two new antimuscarinic agents--darifenacin and solifenacin--are in development. Both show significantly better efficacy compared with placebo for key symptoms of OAB, including urgency. The incidence of dry mouth at the lowest effective dose is 19% for darifenacin and 8% and 14% for solifenacin (2 studies).

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Constipation; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Vision Disorders; Xerostomia

Two newer antimuscarinic anticholinergic drugs--tolterodine and extended-release oxybutynin--are approximately as effective in treating overactive bladder as immediate-release oxybutynin, but are more tolerable. I review clinical trial data on the newer agents.

Topics: Benzhydryl Compounds; Controlled Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Estrogen Replacement Therapy; Female; Humans; Mandelic Acids; Medical History Taking; Middle Aged; Muscarinic Antagonists; Nurse Practitioners; Nursing Assessment; Phenylpropanolamine; Physical Examination; Primary Health Care; Referral and Consultation; Toilet Training; Tolterodine Tartrate; United States; Urinary Incontinence

Overactive bladder (OAB) is a chronic condition that often requires long-term treatment to maintain control of symptoms. A range of therapeutic options are available; however, antimuscarinic agents form the mainstay of treatment. Of these agents, tolterodine and oxybutynin are the most widely used. It is well documented that the immediate-release (IR) formulations of these agents have equivalent efficacy in relieving OAB symptoms. However, tolterodine demonstrates a more favorable tolerability profile, particularly in terms of the frequency and severity of dry mouth. Due to the development of novel drug delivery systems, extended-release (ER) formulations of both oxybutynin and tolterodine are now available, permitting once-daily dosing. The convenience of once-daily dosing of antimuscarinic agents would be expected to improve patient compliance and further relieve the symptoms of OAB. Clinical studies with the ER formulations of tolterodine and oxybutynin demonstrate potential clinical advantages over their respective IR forms in terms of either efficacy or tolerability or both, although the therapeutic index of tolterodine ER appears to show a greater advantage over its IR counterpart compared with oxybutynin ER and its IR form. Importantly, the two ER agents have not been compared directly in a head-to-head clinical study. Overall, available clinical data suggest that the newly developed ER formulation of tolterodine represents a significant therapeutic advancement in the treatment of OAB.

Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urinary Incontinence

Overactive bladder (OAB) is a chronic, distressing condition characterised by symptoms of urgency (sudden overwhelming urge to urinate) and frequency (urinating more than eight times daily), with or without urge urinary incontinence (sudden involuntary loss of urine). It affects millions of people of all ages and both sexes world wide, with greater prevalence in women and the elderly. The treatment of OAB is aimed at reducing debilitating symptoms, which have a significant effect on all aspects of an individual's quality of life, including social, domestic, psychological, occupational, physical and sexual functioning. Anticholinergic agents are currently recommended as first-line therapy for OAB. Their use results in significant clinical improvement in patients, although a lack of selectivity for receptors in the bladder may lead to troublesome side effects, including dry mouth, blurred vision, somnolence, dizziness and constipation. Recent research efforts have focused on developing drugs with a reduced propensity for causing these problems. Of the available anticholinergic agents, oxybutynin and tolterodine are the most widely used to treat OAB. Studies directly comparing tolterodine immediate-release (IR) with oxybutynin IR have shown that the two agents have similar efficacy. However, tolterodine IR is significantly better tolerated, particularly with respect to the incidence and severity of dry mouth. An extended-release formulation of tolterodine (4 mg capsules) has recently been developed to allow for once-daily dosing. In addition to greater convenience, tolterodine extended-release has shown enhanced efficacy and tolerability compared with tolterodine IR.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

Overactive bladder (OAB), the symptom complex of urinary urgency and frequency with or without urge incontinence, affects the lives of millions of Americans. In recent years, more successful treatment options have emerged as advances have been made in understanding the pathophysiologic processes underlying OAB symptoms. However, because most therapeutic modalities for OAB are aimed at symptom resolution, rather than the treatment of distinct pathologic entities, a basic evaluation is required for all patients to establish whether existing (and treatable) pathologic processes are present. In the absence of these processes, symptom relief is both the objective and the outcome used to judge the efficacy of a specific modality. The type of therapy recommended for OAB may depend on several factors including age, existing behavioral patterns, estrogen status, degree of motivation, environmental surroundings, presence of other coexisting urinary symptoms, family support, and patient expectations. This article focuses on methods of identifying patients with OAB, and the role of developing strategies in treating this common disorder.

Topics: Aged; Algorithms; Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Quality Assurance, Health Care; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Age Factors; Aged; Benzhydryl Compounds; Cresols; Frail Elderly; Humans; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Research Design; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

To compare tolterodine with oxybutynin in treatment of urge incontinence.. A systematic review, following Cochrane methods, was performed to retrieve results of randomized trials that compared tolterodine with oxybutynin in adults with urge incontinence. Composite point estimates of efficacy (episodes of incontinence per 24-hour period, frequency, and voided volume) and safety (dry mouth, withdrawal, and dose modification) were calculated.. Four studies were included. Both drugs similarly decreased the number of micturitions in a 24-hour period. Oxybutynin was marginally superior to tolterodine in decreasing the number of incontinent episodes in a 24-hour period (weighted mean difference, 0.41; 95% confidence interval [CI], 0.04 to 0.77) and increasing the mean voided volume per micturition (8.24 mL; 95% CI, 14.19 to 3.38). Fewer patients had dry mouth (relative risk, 0.54; 95% CI, 0.48 to 0.61) and withdrew from the study because of side effects (relative risk, 0.63; 95% CI, 0.46 to 0.88) with tolterodine.. Oxybutynin and tolterodine share a clinically similar efficacy profile (although oxybutynin is statistically superior), but tolterodine is better tolerated and leads to fewer withdrawals as a result of adverse events.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

This analysis reviews clinical trials of the efficacy and safety of tolterodine for use in overactive bladder. It also compares the safety and efficacy of tolterodine and previously available pharmacotherapy. The MEDLINE database (1966 to present) was searched for all English language randomized controlled trials with keyword tolterodine. The search retrieved 10 randomized controlled trials involving tolterodine. Studies ranged from 2 to 12 weeks in duration. Nine trials studied tolterodine vs. placebo, 6 compared tolterodine vs. oxybutynin, 6 compared different doses of tolterodine, and 1 compared immediate-release and extended-release tolterodine. Doses of tolterodine were 0.5-4 mg bid or 4 mg extended-release daily, and doses of oxybutynin were 5 mg bid or tid. All studies found a benefit of tolterodine over placebo in decreasing symptoms of overactive bladder. Parameters significantly improved by tolterodine include number of voids per day, urine volume per void, number of incontinent episodes per day, pad use, maximal cystometric capacity, residual volume, volume at first detrusor contraction, and volume at normal desire to void. Tolterodine 2 mg bid was consistently of equal efficacy as oxybutynin 5 mg tid. Adverse events with both medications were mostly dose-related autonomic nervous system events. The most common adverse event was dry mouth, which was both more frequent and more severe with oxybutynin 5 mg tid than with tolterodine 2 mg bid. Dry mouth did not generally result in discontinuation of medication with either drug. Most drug withdrawal was because of blurred vision or headache. Tolterodine 2 mg bid caused less dose reduction, patient withdrawal, and adverse events, especially dry mouth, compared with oxybutynin 5 mg tid. A single trial found tolterodine extended-release 4 mg/day to have improved efficacy for decreasing urge incontinence episodes along with lower frequency of dry mouth vs. immediate-release tolterodine 2 mg bid. At 4 mg bid, tolterodine caused urinary retention. Neither drug significantly altered any laboratory tests, nor was there clear evidence of electrocardiographic abnormalities induced by either drug. In all randomized controlled trials to date, tolterodine 2 mg bid is an equally effective alternative to oxybutynin 5 mg tid, while causing less intense and less frequent dry mouth or need for treatment withdrawal.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Dose-Response Relationship, Drug; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

A wealth of clinical evidence supports the view that muscarinic receptor antagonists are effective in the treatment of overactive bladder. However, treatment-limiting adverse effects such as dry mouth, constipation, and blurred vision have restricted the usefulness of previously available agents, such as oxybutynin. A real need therefore existed for effective and well-tolerated agents for the long-term management of the troublesome symptoms of overactive bladder. This review outlines the various approaches that have been used in attempts to overcome the tolerability problems of oxybutynin. It also describes how advances in our understanding of muscarinic receptors and bladder function has led to the potential development of either tissue- or subtype-selective antimuscarinic agents with improved tolerability. Drugs that have been developed in this way include tolterodine and darifenacin, each of which shows some bladder selectivity in animal models. Unlike darifenacin, however, the bladder selectivity of tolterodine has been confirmed by numerous clinical studies. Tolterodine's improved tolerability compared with oxybutynin, along with its equivalent therapeutic efficacy at recommended dosages, permits patients to experience the beneficial effects of long-term treatment. Tolterodine therefore represents a real alternative for the long-term management of overactive bladder. The results of ongoing clinical studies with darifenacin are awaited before it can be concluded that selective antagonism of M(3) receptors leads to improved tolerability over existing agents in the treatment of overactive bladder. Similarly, the potential improvements in tolerability associated with different dosage formulations of oxybutynin, and the clinical utility of S-oxybutynin, are yet to be conclusively demonstrated.

Topics: Benzhydryl Compounds; Benzofurans; Clinical Trials as Topic; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Pyrrolidines; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.

Topics: Benzhydryl Compounds; Budgets; Cholinergic Antagonists; Cost of Illness; Cost-Benefit Analysis; Cresols; Drug Costs; Humans; Mandelic Acids; Patient Compliance; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Continued developments in the understanding of lower urinary tract function have led to improvements in the pharmacologic manipulation of bladder dysfunction. Drug delivery changes have produced drugs that provide better efficacy and tolerability, thus improving patient compliance. Improvements in drug delivery systems have altered drug bioavailability and pharmacokinetics. Active current investigation in new agents and delivery systems for intravesical delivery has yielded intriguing early results that may substantially add to the armamentarium for the management of the overactive bladder (urgency, frequency, urge incontinence). New developments in the understanding of the neuropharmacology of the bladder, peripheral pelvic nerves, and sacral cord may provide agents with entirely new drug effects, either as primary agents or agents to be used in combination with currently available drugs. We herein review newer agents and drug delivery systems.

Topics: Adrenergic alpha-Antagonists; Aged; Animals; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Benzilates; Benzofurans; Calcium Channel Blockers; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Drug Administration Routes; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Muscle Relaxants, Central; Nortropanes; Phenylpropanolamine; Pyrrolidines; Tolterodine Tartrate; Urinary Incontinence

Tolterodine is a nonsubtype selective antimuscarinic agent recently approved as therapy in patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. It acts by muscarinic receptor blockade in the bladder wall and detrusor muscle. Despite short terminal disposition half-lives of 2-3 and 3-4 hours for tolterodine and its active 5-hydroxy metabolite, respectively, twice/day dosing is effective due to the drug's prolonged pharmacodynamic effects. Dosage adjustment is recommended in the presence of hepatic impairment and during concurrent therapy with drugs that inhibit cytochrome P450 2D6 and 3A4 isozymes. Tolterodine significantly reduces clinically relevant end points such as number of micturitions and number of incontinence episodes/day. In general, it is superior to placebo and equivalent to oxybutynin in this regard. As might be expected from its pharmacologic profile, the principal adverse effects of the drug are anticholinergic. In clinical trials, tolterodine was tolerated significantly better than oxybutynin. Its relative merits as a first- or second-line agent for patients intolerant of oxybutynin are unclear. Until pharmacoeconomic analyses are conducted that clearly justify use of this more expensive agent, tolterodine is perhaps best reserved for patients who are intolerant of or fail oxybutynin therapy.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Drug Evaluation; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

Topics: Adult; Aged; Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder.. Published articles and abstracts were identified from a MEDLINE search (January 1980-October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration-approved product labeling and the manufacturer were also used in the absence of published data.. Clinical studies of tolterodine involving human subjects were evaluated.. Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents.. Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.

Topics: Animals; Benzhydryl Compounds; Cholinergic Antagonists; Controlled Clinical Trials as Topic; Cresols; Half-Life; Humans; In Vitro Techniques; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

Urgency-type urinary incontinence affects one in four older community-dwelling women and overlaps with other common aging-associated health syndromes such as cognitive impairment, physical mobility impairment, and depression. Observational studies have raised concern about potentially higher rates of delirium and dementia in older adults taking anticholinergic bladder medications, but few prospective data are available to evaluate the effects of these and other pharmacologic treatments for urgency incontinence on cognition and other multisystem functional domains important to older women.. The TRIUMPH study is a randomized, double-blinded, 3-arm, parallel-group trial comparing the multisystem effects of anticholinergic versus beta-3-adrenergic agonist bladder therapy and versus no active bladder anti-spasmodic pharmacotherapy in older women with urgency incontinence. Women aged 60 years and older (target N = 270) who have chronic urgency-predominant urinary incontinence and either normal or mildly impaired cognition at baseline are recruited from the community by investigators based in northern California, USA. Participants are randomized in equal ratios to take identically encapsulated oral anticholinergic bladder therapy (in the form of tolterodine 2 mg extended release [ER]), oral beta-3 adrenergic agonist bladder therapy (mirabegron 25 mg ER), or placebo daily for 24 weeks, with the option of participant-directed dose titration (to tolterodine 4 mg ER, mirabegron 50 mg ER, or matching placebo daily). Participants also receive patient-oriented information and instructions about practicing first-line behavioral management strategies for incontinence. The primary outcome is change in composite cognitive function over 24 weeks assessed by a comprehensive battery of cognitive tests, with a secondary exploration of the persistence of change at 36 weeks. Secondary outcomes include changes over 24 and 36 weeks in domain-specific cognitive function; frequency, severity, and impact of urgency-associated urinary symptoms; physical function and balance; sleep quality and daytime sleepiness; psychological function; and bowel function.. The TRIUMPH trial addresses the need for rigorous evidence to guide counseling and decision-making for older women who are weighing the potential multisystem benefits and risks of pharmacologic treatments for urgency incontinence in order to preserve their day-to-day functioning, quality of life, and independence in older age.. ClinicalTrials.gov NCT05362292. Registered on May 5, 2022.

Topics: Adrenergic Agonists; Aged; Cholinergic Antagonists; Double-Blind Method; Female; Humans; Middle Aged; Multicenter Studies as Topic; Muscarinic Antagonists; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Obstructive sleep apnea syndrome is associated with urological symptoms, including overactive bladder (OAB). This study aims to determine whether combined tolterodine and CPAP therapies are more effective for patients with OSAS than CPAP treatment only.. Women who underwent polysomnography test and were diagnosed with moderate-to-severe OSAS with apnea-hypopnea index (AHI) were included in the study. Data were collected on AHI, OAB awareness-8-item tool (OAB-V8), incontinence questionnaire-urinary incontinence short form (ICIQ-UI-SF), total daily urine volume (DUV), and the Benefit, satisfaction with treatment and willingness (BSW) tool. Eligible patients were randomized to receive either CPAP treatment only or combined CPAP and tolterodine treatment for 3 months.. Among 103 participants, a total of 60 were included. Patients in both treatment arms showed significant improvements in OAB-V8, ICIQ-UI-SF, and total DUV compared to their baseline. The mean OAB-V8 was 15.7 at baseline and 5.6 at 3 months for the combined treatment arm and 16.6 and 7.6 at 3 months for the CPAP group only (mean baseline-adjusted between-group difference -1.1 [95% CI, -12.3 to -7.4]; p < 0.001). The improvement in the mean ICIQ-UI-SF was also statistically more significant in the combined therapy group than in the CPAP only arm (mean baseline-adjusted between-group difference -3.27 [95% CI, -4.6 to -1.59]; p < 0.001). No statistical significance was found in the improvement of total DUV between the groups.. In this study, combined use of tolterodine with CPAP provides beneficial effects to CPAP treatment only regarding OAB symptoms. Further research is required to confirm these findings in a large cohort.

Topics: Continuous Positive Airway Pressure; Female; Humans; Polysomnography; Sleep Apnea, Obstructive; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

First-line behavioral and drug therapies for overactive bladder (OAB) symptoms in men are effective but not usually curative.. To determine whether combining behavioral and drug therapies improves outcomes compared with each therapy alone for OAB in men and to compare 3 sequences for implementing combined therapy.. In this 3-site, 2-stage, 3-arm randomized clinical trial, participants were randomized to 6 weeks of behavioral therapy alone, drug therapy alone, or combined therapy followed by step-up to 6 weeks of combined therapy for all groups. Participants were recruited from 3 outpatient clinics and included community-dwelling men 40 years or older with urinary urgency and 9 or more voids per 24 hours. Data were collected from July 2010 to July 2015 and analyzed from April 2016 to September 2019.. Behavioral therapy consisted of pelvic floor muscle training with urge suppression strategies and delayed voiding. Drug therapy included an antimuscarinic (sustained-release tolterodine, 4 mg) plus an α-blocker (tamsulosin, 0.4 mg).. Seven-day bladder diaries completed before and after each 6-week treatment stage were used to calculate reduction in frequency of urination (primary outcome) and other symptoms (ie, urgency, urgency incontinence, and nocturia). Other secondary outcomes included validated patient global ratings of improvement and satisfaction, Overactive Bladder Questionnaire score, and International Prostate Symptom Score.. Of the 204 included men, 133 (65.2%) were white, and the mean (SD) age was 64.1 (11.1) years. A total of 21 men discontinued treatment and 183 completed treatment. Mean (SD) voids per 24 hours decreased significantly in all 3 groups from baseline to 6-week follow-up (behavioral therapy: 11.7 [2.4] vs 8.8 [2.1]; change, 2.9 [2.4]; percentage change, 24.7%; P < .001; drug therapy: 11.8 [2.5] vs 10.3 [2.7]; change, 1.5 [2.3]; percentage change, 12.7%; P < .001; combined therapy: 11.8 [2.4] vs 8.2 [2.3]; change, 3.6 [2.1]; percentage change, 30.5%; P < .001). Intention-to-treat analyses indicated that posttreatment mean (SD) voiding frequencies were significantly lower in those receiving combined therapy compared with drug therapy alone (8.2 [2.3] vs 10.3 [2.7]; P < .001) but not significantly lower compared with those receiving behavioral therapy alone (8.2 [2.3] vs 8.8 [2.1]; P = .19) and were lower for behavioral therapy alone compared with drug therapy alone (8.8 [2.1] vs 10.3 [2.7]; P < .001). At 12-week follow-up, after all groups had received combined therapy, improvements in mean (SD) voids per 24 hours were also greatest for those receiving initial combined therapy compared with baseline (behavioral therapy: 11.7 [2.4] vs 8.0 [2.2]; change, 3.7 [2.3]; percentage change, 31.6%; P < .001; drug therapy: 11.8 [2.5] vs 8.6 [2.3]; change, 3.2 [2.5]; percentage change, 27.1%; P < .001; combined therapy: 11.8 [2.4] vs 8.0 [2.2]; change, 3.8 [2.1]; percentage change, 32.2%; P < .001), but there were no statistically significant group differences on primary or secondary measures.. Combining behavioral and drug therapy yields greater improvements in OAB symptoms than drug therapy alone but not behavioral therapy alone. When using a stepped approach, it is reasonable to begin with behavioral therapy alone.. ClinicalTrials.gov identifier: NCT01175382.

Topics: Aged; Behavior Therapy; Combined Modality Therapy; Exercise Therapy; Humans; Male; Middle Aged; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urological Agents

To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.. During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.. Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.. Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Benzilates; Blood Pressure; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Nasopharyngitis; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Xerostomia

We evaluated the effect of Tolterodine extended release (TER) versus placebo on bladder wall thickness (BWT) using transvaginal ultrasound in women with overactive bladder (OAB).. We recruited 79 women with symptoms of OAB with a mean age of 47 years who had a BWT of at least 5 mm and a post-micturition volume of less than 50 mL at screening. Subjects received TER 4 mg or placebo once daily for the first 12 weeks of the study. For the subsequent 12 weeks, all subjects received TER 4 mg once daily. BWT was measured at screening, weeks 12 and 24. Subjects recorded number of micturitions, incontinence episodes and urgency episodes, and volume voided per micturition at regular intervals during the study.. Treatment with TER for 12 weeks produced a statistically significant decrease from baseline in BWT (mean [SD] = 0.9 [1.4] mm; P < 0.05) that was not evident following treatment with placebo (0.2 [1.6] mm; P = 0.54). However, the treatment difference did not reach statistical significance (LS Mean = -0.4; 95%CI: -1.2, 0.3; P = 0.25). After 12 weeks of treatment, subjects who had taken TER showed an improvement in each bladder diary variable compared to placebo-treated subjects.. TER may have a direct effect on BWT in women with OAB. Larger studies are warranted to further investigate the effect of behavioral interventions and antimuscarinics, such as TER, on BWT in women with OAB and increased BWT.

Topics: Adolescent; Adult; Age Factors; Aged; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Middle Aged; Muscarinic Antagonists; Placebo Effect; Tolterodine Tartrate; Treatment Outcome; Ultrasonography; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Young Adult

The analysis of the results of a multicenter, open, randomized comparative phase III clinical trial on the use of imidafenacin for treating patients with OAB was carried out. A clinical study was conducted according to GCP standards in 12 urological centers of the Russian Federation with the support of company AO "R-Pharm".. A total of 296 patients (men and women) aged from 18 to 65 years with OAB and urgent urinary incontinence were included in the study. All patients were randomized into two groups. In Group 1 (n=148) patients received -cholinoblocker imidafenacin 1 tablet (0,1 mg) twice a day. Group 2 patients (n=148) were prescribed a comparison drug tolterodine 1 tablet (2 mg) twice a day, as well. The duration of treatment was 12 weeks.. The analysis of results showed a significant decrease in the OAB symptoms in both groups. In Group 1 a decrease of episodes of urge urinary incontinence was more pronounce compared to Group 2, as well as amount of day-time and night-time of episodes of urge urinary incontinence by the 2nd, 4th, 8th and 12th weeks of treatment in comparison with baseline scores. There were no differences between two groups in the severity of reducing average urinary frequency per day. Reducing the severity of urinary disturbances in patients of both groups was accompanied by an improvement in the quality of life. There was a significant and similar decrease in the average total score of both OAB Awareness Tool and EQ-5D questionnaires. Tolerability of treatment was satisfactory in both groups and there were no differences in the adverse events in Group 1 and 2.. Imidafenacin showed high clinical efficacy for treating patients with OAB, which is not inferior, and in some values, is superior in comparison to tolterodine. Both drugs had a similar safety and tolerability profile.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Imidazoles; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Russia; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Young Adult

To assess the characteristics of tolterodine extended-release (ER) 4 mg responders and suboptimal responders (≤50% decrease in UUI episodes/24 h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8 mg in tolterodine suboptimal responders.. Adult patients with OAB symptoms for ≥6 months and ≥8 micturitions, and ≥2 and <15 UUI episodes/24 h at week -2 received open-label tolterodine ER 4 mg during a 2 week run-in. Suboptimal responders after tolterodine treatment (week 0) were randomized to fesoterodine (4 mg for 1 week, 8 mg for weeks 2-12) or placebo once daily. Post-hoc analyses compared the percentage change from week -2 to week 0 in UUI episodes/24 h in tolterodine responders versus suboptimal responders and identified significant predictors of a UUI response at week 12 with fesoterodine 8 mg among tolterodine suboptimal responders.. Of 897 patients, 610 (68%) were UUI suboptimal responders during the run-in period. UUI episodes/24 h at week -2 were similar in tolterodine responders and suboptimal responders (4.2 vs. 4.3), but responders showed a significantly greater median percentage decrease in UUI episodes/24 h after tolterodine treatment at week 0 (80.0% versus 15.3%; p < .0001). During double-blind treatment, the percentage of patients with a UUI response at week 12 was significantly greater with fesoterodine (69.9%) than placebo (57.0%; p = .0027). Fesoterodine (vs. placebo), no previous antimuscarinic use before tolterodine run-in, and less UUI severity at baseline were significant predictors of a UUI response.. For patients with OAB, including UUI, who were treated initially with tolterodine and showed a suboptimal UUI response, nearly 70% demonstrated a UUI response with second-line fesoterodine 8 mg. No antimuscarinic use before tolterodine and fewer baseline UUI episodes were significant predictors of a UUI response with fesoterodine.

Topics: Adult; Aged; Benzhydryl Compounds; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

To compare the efficacy of pelvic floor muscle exercises (PFME) using weighted vaginal cones (WVC) on the symptoms, clinical findings, urodynamic findings and quality of life (QoL) in overactive bladder (OAB) patients with tolterodine.. Thirty-nine patients with urinary frequency (≥ 8/day), nocturia (≥ 2/night), urgency and a total score of ≥ 8 to the overactive bladder-awareness tool (OAB-V8) were diagnosed as OAB and were randomized into two treatment groups; WVC and extended release tolterodine (tolterodine ER) 4 mg/day for 8 weeks. Results of the clinical findings, 3-day urinary diary, validated questionnaires for symptom bother and QoL (Urinary distress inventory (UDI-6), incontinence impact questionnaire (IIQ-7), OAB-V8, Wagner questionnaire) and urodynamic examination before and after treatment were compared.. A reduction of frequency, nocturia and urinary incontinence was observed in WVC group (p=0.006, p=0.034 and p=0.008, respectively) and in tolterodine group (p<0.001, p=0.002 and p=0.035, respectively). 24-h dry pad test results were improved significantly in both groups (p=0.003 and p=0.001, respectively). Pelvic muscle strength was significantly improved in WVC group but not in tolterodine group (p=0.010 and p=0.180, respectively). UDI-6, IIQ-7, OAB-V8 scores were improved significantly in both groups. Improvements in Wagner questionnaire were observed in WVC group but not in tolterodine group (p=0.002 and p=0.591, respectively). First sensation of bladder filling was significantly improved after WVC treatment but not in tolterodine group (p=0.035 and p=0.550, respectively). After treatment, detrusor overactivity (DO) resolved in 8 patients in the WVC group (p=0.003) and in 2 patients in the tolterodine group (p=0.426).. WVC treatment seems to be an efficacious therapeutic option for the improvement of overactive bladder syndrome (OABS).

Topics: Adult; Female; Humans; Middle Aged; Muscarinic Antagonists; Nocturia; Pelvic Floor; Physical Therapy Modalities; Quality of Life; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics; Vagina

To investigate the prevalence of detrusor after-contraction (DA-C) in children with posturination dribbling, and compare the outcomes of pharmacological treatment and pelvic floor biofeedback training.. Children with posturination dribbling underwent urodynamic studies. Patients with DA-C were randomly allocated to one of two groups: pelvic floor biofeedback training or 1 mg tolterodine, orally, twice daily. Treatment was continued for 12 weeks.. The study included 45 children. DA-C was present in 39 patients (86.6%), 30 (76.9%) of whom also exhibited detrusor overactivity. Pelvic floor biofeedback training resulted in a significantly better response than tolterodine, in terms of reduction in the number of posturination dribbling events in the month after completion of treatment.. DA-C is closely associated with posturination dribbling in children. Pelvic floor biofeedback training should be considered the initial treatment option in these patients.

Topics: Adolescent; Benzhydryl Compounds; Biofeedback, Psychology; Child; Cresols; Female; Humans; Male; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Pelvic Floor; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

Various antimuscarinic agents have been developed for the treatment of overactive bladder (OAB). More data comparing these agents are still required. This study evaluated the efficacy and safety of solifenacin and tolterodine in Taiwanese patients with OAB symptoms.. This was a prospective, randomized, open-label study. A total of 75 patients (25 men and 50 women) with OAB symptoms were randomized to treatment with solifenacin (n = 39) or tolterodine (n = 36). Efficacy and safety variables were assessed and compared with the baseline and between the two groups.. At week 12, solifenacin and tolterodine demonstrated equal efficacy in reducing the number of micturition (-2.56 ±3.31 vs. -2.44 ± 4.56, p = 0.58), urgency (-1.70 ± 3.07 vs. -1.15 ± 2.68, p =0.37) and incontinence (-2.79 ± 2.82 vs. -4.67 ± 9.29, p =0.28) episodes per 24 hours. There was no difference in improvement of the quality of life. The patient and physician assessments of treatment benefit were not statistically different for solifenacin and tolterodine (p = 0.23 and p = 0.52, respectively), with the majority showing benefits in both groups. The incidence of major adverse events, including dry mouth (18.0%vs. 8.3%, p = 0.31) and constipation (12.8%vs. 2.8%, p = 0.20) was not significantly different. Compared with baseline, the severity of dry mouth did not increase in either group.. Both solifenacin and tolterodine are effective in treating key OAB symptoms, including urinary frequency, urgency and incontinence in the Taiwanese population. Both medications are comparably effective and safe, with the most common adverse effects being dry mouth and constipation.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Quinuclidines; Solifenacin Succinate; Taiwan; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination

To assess efficacy and tolerability of tolterodine extended release (ER) in continent and incontinent subjects with overactive bladder (OAB).. This was a post hoc analysis of data from a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily). Subjects completed 7-day bladder diaries at baseline and week 12; those with one or more incontinence episode(s) in their diaries at baseline were considered incontinent. Subjects rated urgency associated with each micturition on a scale from 1 to 5, and micturitions were categorized post hoc by urgency rating as non-OAB (1-2), OAB (3-5), or severe OAB (4-5).. At baseline, 40% of subjects were incontinent. Tolterodine ER (n = 429) reduced total, OAB, and severe OAB micturitions compared with placebo (n = 421) in continent and incontinent subjects. There was no difference between continent and incontinent subjects in terms of the magnitude of improvement with tolterodine ER relative to placebo for total, OAB, and severe OAB micturitions. Reductions in mean urgency and frequency-urgency sum ratings were significantly greater in the tolterodine ER group. Among incontinent subjects, tolterodine ER significantly reduced urgency urinary incontinence episodes and significantly increased the percentage of subjects achieving continence relative to placebo. Adverse event rates were low in both continent and incontinent subjects.. Tolterodine ER reduced micturitions associated with urgency (OAB or severe OAB) in both continent and incontinent subjects. Tolterodine ER also reduced urgency urinary incontinence episodes in incontinent subjects. These data show that tolterodine ER is effective and well tolerated in both continent and incontinent subjects with OAB.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Placebos; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination

Quality of life studies indicate that overactive bladder (OAB) has a greater negative impact on everyday life than other serious conditions such as diabetes. The detrimental effect of OAB on female sexual health is more prominent than urinary incontinence. We know that tolterodine immediate release (IR) has a beneficial effect on urinary symptoms in OAB.. To evaluate the impact of tolterodine IR on sexual function in patients with OAB.. A total of 30 sexually active women with OAB from 20 to 52 years were included. All patients filled out the International Consultation on Incontinence Questionnaire (ICIQ) and the Arizona Sexual Experience Scale (ASEX) before treatment with tolterodine IR and at the end of each month of treatment until 3 months.. Expected outcomes were improvements in the ICIQ and ASEX total score. All ASEX items were expected to improve individually. These improvements indicate better sexual function after treatment. Results. The mean of the total ASEX score improved relative to baseline in the first (P<0.01), second (P<0.01), and third (P<0.01) follow-up. The mean of scores for sexual desire, arousal, vaginal lubrication, orgasm, and orgasm satisfaction improved significantly (P<0.01) with each follow-up.. Tolterodine IR significantly improves sexual function of women with OAB. Improvement is seen in all domains of sexual function.

Topics: Adult; Arousal; Benzhydryl Compounds; Cresols; Female; Humans; Libido; Middle Aged; Muscarinic Antagonists; Orgasm; Phenylpropanolamine; Quality of Life; Sexual Behavior; Sexual Dysfunction, Physiological; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence; Young Adult

To describe the design of a multi-center randomized clinical trial of behavioral training combined with drug therapy for the treatment of urge incontinence. The study aims are to determine whether adding behavioral training will increase the number of women who can discontinue drug therapy and sustain a significant reduction of incontinence; to test whether the short-term effectiveness of drug therapy can be enhanced by combining it with behavioral training; and to determine the cost-effectiveness of combined therapy.. Two-stage randomized clinical trial currently being conducted by the Urinary Incontinence Treatment Network, a clinical trials network established by the National Institutes of Health.. Participants are 307 community-dwelling women with pure or predominant urge incontinence. Stage 1 consists of 10 weeks of drug therapy with sustained-release tolterodine alone or combined with behavioral training (pelvic floor muscle exercise training, bladder control techniques, fluid management). In stage 2, drug is withdrawn and behavioral training stopped. The primary outcome, measured at 8 months, is a composite of two endpoints (1) successful drug withdrawal (i.e. not requesting any other treatment for incontinence) and (2) achieving and maintaining > or =70% reduction in the frequency of incontinence episodes on bladder diary. The effects of treatment and drug withdrawal are measured at week 10 and months 4, 6, 8, 14, 20, and 26. Assessments include: the Medical Epidemiological and Social Aspects of Aging (MESA) incontinence questionnaire, pelvic floor muscle strength assessment, Incontinence Impact Questionnaire, Urogenital Distress Inventory, Overactive Bladder Questionnaire, Short-Form Health Survey (SF-12), costs associated with incontinence care, Health Utility Index Mark 3, Willingness to Pay Scale, and Patient Satisfaction Questionnaire.. The BE-DRI study is the first clinical trial to investigate the use of drug therapy combined with behavioral therapy with the pre-established goal of discontinuing the medication. The concept of drug cessation represents a new paradigm in this field of research and has important implications for future treatment approaches to urge incontinence.

Topics: Adult; Behavior Therapy; Benzhydryl Compounds; Cresols; Exercise Therapy; Female; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Research Design; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Although the majority of patients with overactive bladder (OAB) are continent, most patient-reported outcome measures for OAB were designed for patients with urinary incontinence. The overactive bladder questionnaire (OAB-q) was developed to assess symptom bother and HRQL among both continent and incontinent OAB patients; however, the responsiveness of the OAB-q among continent patients has not been evaluated. The purpose of this analysis was to assess the responsiveness of the OAB-q among OAB patient subgroups with a focus on continent patients.. Post-hoc analyses were conducted from two 12-week trials of tolterodine for the treatment of OAB. Patients completed the OAB-q and daily bladder diaries (assessing frequency, urgency, and incontinence episodes) at baseline, 4 weeks, and 12 weeks. Three patient subgroups were identified on the basis of continence status at all three timepoints: (1) continent; (2) incontinent; and (3) incontinent at baseline and continent by Week 12 (ITC). General linear models were used to compare changes from baseline, and Spearman correlations assessed the association between OAB-q changes and bladder diary changes. Effect sizes were computed separately for each group.. A total of 262 continent, 552 incontinent, and 397 ITC patients were included in this analysis. Continent patients tended to be younger than incontinent patients, and patients were predominantly female, although continent patients had the highest percentage of male patients in both studies. Compared with continent patients, patients who were incontinent at baseline tended to have greater symptom bother and lower HRQL at baseline. All OAB-q change scores were consistently greatest for the ITC group (12.1-33.9), and greater for continent patients (10.8-28.6) than for incontinent patients (7.6-20.1). All three groups of patients experienced reductions in frequency and urgency episodes, and these changes were significantly correlated with changes in the OAB-q scales. Among all three groups, effect sizes were in the moderate-to-large range for all OAB-q subscales except Social Interaction.. The OAB-q is highly responsive to change between continent and incontinent patients with OAB, and is a valid tool for measuring treatment outcomes among continent OAB patients.

Topics: Adaptation, Psychological; Aged; Benzhydryl Compounds; Cresols; Female; Humans; Male; Medical Records; Middle Aged; Muscarinic Agonists; Phenylpropanolamine; Sex Characteristics; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination

We have studied the association between various symptoms, bother, and patient treatment satisfaction in overactive bladder (OAB).. Episodes of urgency, incontinence, daytime frequency and nocturia and responses to the patient perception of bladder condition scale, the urgency perception scale, and visual analog scales of limitations in daily life and of treatment satisfaction were evaluated in 3,824 OAB patients at baseline and during 9 months treatment with tolterodine ER (4 mg q.d.) in an open-label, observational study. Relationships amongst number of symptoms/ 24 hr and scales were explored. Treatment satisfaction was correlated with improvements in symptoms and scales.. At baseline, the number of episodes of the four OAB symptoms correlated only poorly with each other and with the two bother-related scales, while the two scales assessing bother correlated much stronger with each other. Factor analysis identified four components which described "bother," "incontinence," "urgency/frequency," and "nocturia" and in combination explained 81.9% of the total variance. The component "bother" had the strongest individual effect accounting for 42.1% of the total variance. While improvements of symptoms and bother were seen with tolterodine treatment, patient treatment satisfaction correlated strongest with improvements of the two bother-related scales.. We conclude that the counting of episodes of OAB symptoms only insufficiently describes the afflicted patients. Patient bother is the strongest individual component but only poorly explained by episodes of the four symptoms defining OAB. Alterations of bother may better reflect patient-relevant outcomes in OAB treatment than alterations in the number of symptom episodes.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cluster Analysis; Cresols; Delayed-Action Preparations; Factor Analysis, Statistical; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Nocturia; Patient Satisfaction; Phenylpropanolamine; Principal Component Analysis; Statistics, Nonparametric; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To examine the continence ('dryness') rate as an outcome measure of the efficacy of antimuscarinic treatment, and to explore how changes in bladder diary duration, baseline severity of urinary incontinence (UI), and study population characteristics affected this outcome.. Urgency UI is a symptom of overactive bladder (OAB) and antimuscarinic agents are a first-line treatment for OAB symptoms; several studies have used dryness rate as an efficacy endpoint, calculated as the percentage of patients who record no UI episodes in a diary period. We performed a post hoc analysis of data from a 12-week, multicentre, randomized, double-blind, placebo-controlled trial of tolterodine extended-release (ER) in patients with symptoms of urinary frequency (> or =8 voids/24 h) and urgency UI (> or =5 episodes/week). Patients with stress UI were excluded. Diary entries from the 3-, 5-, and 7-day periods immediately preceding the baseline and the week 12 visit were used to assess the relationships between the percentage of patients reporting total dryness at week 12, diary duration (3, 5, or 7 days), baseline number of weekly UI episodes (1-6, 7-13, 14-20, > or = 21), and population analysed (intent-to-treat, ITT, or per protocol, PP). The mean changes in weekly UI episodes from baseline to week 12 are also reported by diary duration and baseline frequency of UI for patients treated with tolterodine-ER.. The total dryness rates decreased with increasing diary duration and greater frequency of UI at baseline. Analysis of the ITT population also showed lower dryness rates than the PP population. However, the mean reductions in weekly UI episodes for the ITT and PP populations were consistent across diary duration for each level of baseline UI frequency.. 'Dryness' varies with diary duration, baseline frequency of UI, and the population analysed. Comparisons of dryness rates between studies might lead to erroneous conclusions when these factors are not considered.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Medical Records; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Early studies of extended-release oxybutynin in patients with overactive bladder used adjusted-dose regimens ranging from 5 to 30 mg/day to achieve an optimal balance of efficacy and tolerability. The safety and tolerability of extended-release oxybutynin at a fixed dose of 10 mg once daily (commonly prescribed in clinical practice) is reported using pooled data from 2 multicenter, randomized, double-blind, parallel-group trials with a similar study design. One study compared extended-release oxybutynin with immediate-release tolterodine 2 mg bid. The other study compared extended-release oxybutynin with extended-release tolterodine 4 mg qd. In total, 576 patients received extended-release oxybutynin, 399 received extended-release tolterodine, and 193 received immediate-release tolterodine. The incidence of adverse events (AEs) was similar in the three treatment groups (extended-release oxybutynin, 70%; extended-release tolterodine, 64%; and immediate-release tolterodine, 79%). The most common adverse event was dry mouth (extended-release oxybutynin, 29%; extended-release tolterodine, 22%; and immediate-release tolterodine, 33%). Other AEs occurring in more than 5% of patients in any treatment group included constipation, diarrhea, headache, urinary tract infection, pain, dyspepsia, and peripheral edema, with no apparent difference across treatment groups. Most AEs (>90%) were mild or moderate in intensity in all treatment groups. The proportion of patients who discontinued study medication due to AEs was 6.1, 4.8, and 7.8% in the extended-release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively. In total, 1.2, 1.0, and 1.6% of patients in the extended-release oxybutynin, extended-release tolterodine, and immediate-release tolterodine groups, respectively, discontinued study medication due to dry mouth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

To assess the 24-h efficacy of tolterodine extended-release (ER) in patients with overactive bladder (OAB) and urgency urinary incontinence (UUI).. We conducted a post hoc analysis of a 12-week, placebo-controlled trial of tolterodine-ER in patients with frequency (> or =8 voids/24 h) and UUI (> or=5 episodes/week) for > or = 6 months. Seven-day bladder diaries were used to record diary endpoints; 24-h diary data were stratified by 6-h periods beginning at midnight.. Compared with placebo (508 patients), tolterodine-ER (507 patients) significantly and consistently increased volume voided per void and reduced UUI episodes and micturition frequency during each interval.. These results indicate that tolterodine-ER maintained clinical efficacy over 24 h and should be effective for OAB symptoms without regard to whether symptoms occur during the day or at night.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Medical Records; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

To determine the efficacy, tolerability, and safety of fesoterodine in subjects with overactive bladder (OAB).. This was a multicentre, randomised, double-blind, placebo- and active-controlled trial with tolterodine extended release (ER) to assess the efficacy and safety of fesoterodine. Eligible subjects (> or =18 yr) with increased micturition frequency and urgency and/or urgency urinary incontinence (UUI) were randomised to placebo, fesoterodine 4 mg, fesoterodine 8 mg, or tolterodine ER 4 mg for 12 wk. The primary efficacy variable was a change from baseline to week 12 in micturitions per 24 h. Co-primary end points included change from baseline to week 12 in UUI episodes per 24 h and Treatment Response ("yes" or "no," based on four-point treatment benefit scale). Secondary efficacy variables included mean volume voided per micturition, continent days per week, and number of urgency episodes.. At the end of treatment, subjects taking fesoterodine 4 and 8 mg had significant (p<0.05) and clinically relevant improvements versus placebo in the primary, co-primary, and most secondary efficacy variables. Tolterodine ER (active control) also provided significantly greater improvement than placebo for most efficacy variables, confirming the sensitivity of the study design. A more pronounced effect was observed with fesoterodine 8 mg at most end points.. Both doses of fesoterodine were significantly better than placebo in improving the symptoms of OAB and produced a significantly greater Treatment Response versus placebo. Efficacy was more pronounced with fesoterodine 8 mg compared with the other treatments. Active treatments were well tolerated.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Selection; Phenylpropanolamine; Safety; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence; Urination

Bladder discomfort related to intraoperative catheterization of urinary bladder is a distressing symptom and more so in patients awakening from anaesthesia. These symptoms are similar to symptoms of overactive bladder. Muscarinic receptor antagonists have been reported to be effective in the treatment of overactive bladder. This study was therefore undertaken to evaluate the efficacy of oxybutynin and tolterodine in preventing catheter related bladder discomfort.. Two hundred and thirty-four consecutive adult patients, ASA I and II, of either sex, undergoing elective percutaneous nephrolithotomy surgery requiring urinary bladder catheterization were randomized into three equal groups of 78 each. Group C (control) received placebo, Group O (oxybutynin) received oxybutynin 5 mg and Group T (tolterodine) received tolterodine 2 mg orally 1 h before surgery. After induction of anaesthesia patients were catheterized with a 16 Fr Foley's catheter and the balloon was inflated with 10 ml distilled water. The bladder discomfort was assessed at 0, 1, 2 and 6 h after patient's arrival in the post-anaesthesia care unit. Severity of bladder discomfort was graded as mild, moderate and severe.. Incidence of bladder discomfort observed in the control group was higher, i.e. 58% (45/78), compared with oxybutynin and tolterodine groups where it was 35% (28/78) and 33% (26/78), respectively (P<0.05). Significant reduction in the severity of bladder discomfort was also observed after oxybutynin and tolterodine therapy compared with control (P<0.05).. Pretreatment with either oxybutynin or tolterodine reduces the incidence and severity of catheter related bladder discomfort.

Topics: Adult; Anti-Infective Agents, Urinary; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Intraoperative Care; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nephrostomy, Percutaneous; Phenylpropanolamine; Postoperative Complications; Prospective Studies; Severity of Illness Index; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Catheterization; Urinary Incontinence

Antimuscarinic therapy for men with OAB and BOO is perceived as a potential risk for urinary retention. Using pressure flow urodynamics, we evaluated the safety of tolterodine vs placebo in men with OAB and BOO.. Men (older than 40 years) with BOO and confirmed detrusor overactivity were randomized to tolterodine (2 mg twice daily in 149) or placebo (in 72) for 12 weeks. Primary end points were Qmax and pdetQmax.. Median treatment differences in Qmax (-0.7 ml per second, 95% CI -1.6 to 0.4) and pdetQmax (-7 cm H2O, 95% CI -3 to 11) were comparable. Tolterodine significantly reduced the BOOI vs placebo (-9 vs 0, p < 0.02). There were significant treatment differences in volume to first detrusor contraction (+59 ml, 95% CI 19-100) and maximum cystometric capacity (+67 ml, 95% CI 35-103), favoring tolterodine over placebo (p < 0.003). Change in PVR was significantly greater among patients treated with tolterodine (+25 ml) than placebo (0 ml, p < 0.004). There were no significant between-group differences in the incidence of adverse events. Urinary retention was reported by 1 patient treated with placebo.. Tolterodine did not adversely affect urinary function in men with OAB and BOO. Urinary flow rate was unaltered, and there was no evidence of clinically meaningful changes in voiding pressure and PVR or urinary retention. Tolterodine was well tolerated. These results suggest that antimuscarinics can be safely administered in men with BOO.

Topics: Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urinary Incontinence

Treatment with anticholinergic agents is the mainstay of therapy for detrusor instability (DI), a chronic and morbid condition characterized by urge urinary incontinence. The aim of this study is to assess the effectiveness and tolerability of tolterodine and oxybutynin in children with DI.. A total of 60 children with DI were enrolled, 30 (14 male, 16 female, mean age 7.97+/-2.71 years) in the tolterodine group and 30 (12 male, 18 female, mean age 7.33+/-2.23 years) in the oxybutynin group. In this prospective study we reviewed data from 60 children followed for at least 6 months. All of the patients in the study population had a history of dysfunctional voiding. Urodynamic investigations were conducted in all of the patients before and after anticholinergic treatment. Episodes of urge urinary incontinence and adverse events were also evaluated.. Improvements in urge incontinence episodes were similar for the children who received tolterodine or oxybutynin. Improvements in the urodynamic parameters were also the same in the two groups. Adverse events were significantly lower in the tolterodine group (13 events in 13 patients) compared to the oxybutynin group (27 events in 20 patients; P=0.027).. Reductions in urge urinary incontinence episodes were similar with tolterodine and oxybutynin in children with DI. Side-effects were more common with oxybutynin. Treatment of children with DI with tolterodine shows significantly better tolerability and this may enhance children's compliance during long-term treatment.

Topics: Benzhydryl Compounds; Child; Child, Preschool; Cresols; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Urinary Incontinence

To evaluate the efficacy and tolerability of nighttime tolterodine dosing on urgency-related micturitions in patients with overactive bladder (OAB) and nocturia.. This was a 12-week randomized controlled study of 850 patients given 4 mg tolterodine extended release (TER) or placebo once daily 4 hours or less before bed. Patients with eight or more micturitions/24 hours and a mean of 2.5 episodes/night or more were included. Changes in the number of nighttime and 24-hour micturitions were analyzed by urgency rating per micturition. The urgency per micturition was recorded in 7-day diaries using a 5-point rating scale (score 1 to 5). Each micturition was classified according to the following urgency rating categories: total (1 to 5), non-OAB (1 to 2), or OAB (3 to 5). OAB-related micturitions were further classified as nonsevere (score 3) and severe (score 4 to 5).. TER reduced the total number of nocturnal micturitions, but, compared with placebo, this difference was not statistically significant. However, TER did significantly reduce OAB-related and severe OAB-related nocturnal micturitions compared with placebo. TER had no effect on non-OAB micturitions. TER significantly reduced the total, OAB, and severe OAB micturitions during 24-hour and daytime intervals compared with placebo. Significantly more TER-treated than placebo-treated patients reported a treatment benefit and willingness to continue treatment. Adverse events associated with nighttime dosing of TER versus placebo were few.. TER significantly reduced OAB-related micturitions during 24-hour, daytime, and nighttime intervals. TER did not affect normal (non-OAB) micturitions. Nighttime dosing with TER was associated with few adverse events and adverse event-related withdrawals. The 24-hour efficacy of TER was maintained with nighttime dosing.

Topics: Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

A group of authors from the USA evaluated the efficacy and tolerability of tolterodine extended-release on objective and subjective endpoints in men with an overactive bladder. They found that it significantly reduced incontinent episodes and improved patient perception of treatment benefit in men with an overactive bladder. To evaluate the efficacy and tolerability of tolterodine extended-release (ER) on objective and subjective endpoints in men with overactive bladder (OAB) and urgency urinary incontinence (UI). PATIENTS AND METHODS This was a post hoc analysis of data collected from men with OAB enrolled in a 12-week, double-blind, placebo-controlled trial of tolterodine ER (4 mg once daily; tolterodine ER registration trial) and included men with urinary frequency (> or =8 micturitions/24 h) and urgency UI (> or =5 episodes/week). UI episodes were assessed using 7-day bladder diaries. Patient perception of treatment benefit was evaluated after 12 weeks. Adverse events (AEs) were recorded throughout the study.. In all, 163 men with OAB (placebo, 86; tolterodine ER, 77; mean age 65 years) were evaluated. Baseline demographics and clinical characteristics were similar for the two treatment groups. Compared with placebo, tolterodine ER significantly reduced weekly UI episodes (median % change, -71% vs - 40%, P < 0.05; mean numeric change, - 11.9 vs -5.9, P = 0.02). Men receiving tolterodine ER had fewer micturitions/24 h, but this was not a significant difference from placebo (median % change, -12% vs - 4%, P = 0.22). Significantly more men treated with tolterodine-ER (63%) than placebo-treated men (46%) reported a benefit of treatment after 12 weeks (P = 0.04). The most commonly reported AEs associated with tolterodine-ER vs placebo were dry mouth (16% vs 7%), constipation (4% vs 9%), dyspepsia (4% vs 1%), dizziness (5% vs 1%), and somnolence (3% vs 1%). One of the men receiving tolterodine ER had symptoms suggestive of urinary retention that led to his withdrawal from the study. None of the men had acute urinary retention requiring catheterization.. In men with OAB and urgency UI, tolterodine ER was well tolerated and significantly reduced episodes of urgency UI, and improved patient perception of treatment benefit.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

We evaluated the effect of tolterodine extended release (ER) on patient- and clinician-reported outcomes in a primary care setting. Patients had overactive bladder (OAB) symptoms for >or=3 months and were at least moderately bothered by their most bothersome symptom, as indicated on the patient-completed OAB Bother Rating Scale. Patients completed the Overactive Bladder Questionnaire (OAB-q), American Urological Association Symptom Index (AUA-SI), and Patient Perception of Bladder Condition at each visit; investigators completed the Clinical Global Impression-Improvement at week 12. By week 12, there were statistically significant and clinically meaningful decreases on the OAB-q and AUA-SI total and subscale scores (p < 0.0001). Seventy-nine per cent of patients experienced some improvement in their overall bladder condition. Physicians reported that 68% of patients were 'much improved' or 'very much improved'. For symptom-defined conditions, patient-reported outcomes are a valuable means for determining responses to treatment.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

The dosage of the antimuscarinic drugs: Tolterodine ER or Trospium was increased to a higher-than-recommended dosage in patients where the manufacturer's recommended dosage had failed. All patients were suffering from neurogenic detrusor overactivity incontinence. Tolerability and success were evaluated in the present study.. Twenty-one patients with neurogenic detrusor overactivity were evaluated: 17 with spinal cord injury, 3 with multiple sclerosis, and 1 with a meningomyelocele. All patients catheterized themselves or were catheterized. If neurogenic detrusor overactivity continued and the medication was well tolerated, the dosage was doubled to either 8 mg of Tolterodine ER [2 x 4 mg (n = 11)] or 90 mg of Trospium [3 x 30 mg (n = 10)]. The follow-up was monitored by a bladder diary and urodynamic evaluation.. Sixteen patients significantly decreased their incontinence episodes from 8-12 episodes before to 0-2 episodes during the doubled treatment. The reflex volume increased from 202 +/- 68 to 332 +/- 50 ml (P < 0.001). Cystometric capacity enlarged from 290 +/- 56 to 453 +/- 63 ml (P < 0.001). One patient had to stop the medication because of intolerable side effects and five patients did not experience satisfactory benefit.. The increased dosage of Tolterodine or Trospium is an effective treatment in patients with neurogenic bladder.

Topics: Adolescent; Adult; Benzhydryl Compounds; Benzilates; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Muscle Hypertonia; Nortropanes; Parasympatholytics; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence; Urodynamics

To evaluate the efficacy and safety of nighttime dosing with tolterodine extended release (TER) in men with overactive bladder (OAB) and nocturia.. This was a post hoc analysis of data from two 12-week, double-blind, placebo-controlled trials of nighttime (<4 hours before bedtime) TER (4 mg daily) dosing. Men with a mean micturition frequency of eight or more times in 24 hours, including a mean of 2.5 or more nocturia episodes/night, were included. For each micturition, patients used 7-day diaries to record urinary urgency on a 5-point urgency rating scale (1, none; 2, mild; 3, moderate; 4, severe; 5, urgency urinary incontinence). Micturitions were analyzed post hoc by urgency rating categories: total (1 to 5), non-OAB (1 to 2), OAB (3 to 5), and severe OAB (4 to 5). Adverse events were recorded throughout the study.. A total of 745 men (mean age 64 years) were randomized to placebo (n = 374) or TER (n = 371). Of the 745 men, 73% reported no incontinence episodes in a 7-day diary at baseline. At week 12, the weekly values for nighttime severe OAB micturitions and 24-hour and daytime total, OAB, and severe OAB micturitions were significantly reduced in the TER group versus the placebo group. The TER-treated men also reported a significant reduction in the mean urgency rating versus placebo. Adverse events associated with TER were low and comparable to those in the placebo group, with the exception of dry mouth (11% versus 4%). Withdrawals because of adverse events were infrequent (3% TER, 4% placebo). Five men were withdrawn for symptoms suggestive of urinary retention (3 TER, 2 placebo).. Nighttime TER dosing reduced urgency-related micturitions and was well tolerated in men with OAB and nocturia.

Topics: Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Urination Disorders

To determine whether women with urinary incontinence (UI) can identify their allocation in a randomized controlled trial (RCT) of tolterodine (TOL), and whether correct identification is associated with outcomes and adverse effects (AEs).. Exploratory analysis of a randomized, double-blind, placebo (PLC)-controlled trial of TOL 4 mg daily for 8 weeks in 743 women with urge-predominant mixed UI. Patient perception of their randomization was assessed at trial end. Main outcome measures were 7-day bladder diaries, patient perception of improvement, and UI-specific quality of life (QoL).. TOL produced a significant decrease in urge UI episodes compared to PLC (78% vs. 51%, P = 0.0001). Fifty-one percent of women correctly identified their randomization (58% on TOL vs. 37% on PLC, P < 0.001). Women who assumed they took TOL had better bladder diary outcomes than those who assumed they took PLC. Within each assumption group, patient perception outcomes were similar, regardless of actual randomization. QoL improved in all domains except general health for women on TOL. In women who assumed they took TOL, significant drug benefit was evident in three domains. Moderate-severe dry mouth was higher in those who assumed they took TOL (7.3% vs. 0%, P < 0.0001).. Greater than fifty percent of women in this RCT of antimuscarinic treatment were "unblinded" to their randomization. Patient assumption of randomization was associated with bladder diary and perception outcomes, specific QoL domains, and dry mouth. Efficacy of urge incontinence drugs should be considered in the context of patient assumptions, expectations, and "unblinding" by easily evident side effects.

Topics: Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Medical Records; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

To ascertain the validity and responsiveness of the Urgency Perception Scale (UPS) as an indicator of perceived urinary urgency.. The UPS was developed to assess perceived urinary urgency in clinical studies evaluating the efficacy of the antimuscarinic drug, tolterodine, for treating the overactive bladder (OAB) syndrome. Secondary analyses of clinical and patient assessment data from three clinical studies of tolterodine were conducted to evaluate the UPS. Construct validity was assessed by correlations between the UPS and patient voiding diary variables and other patient assessments, including: perception of bladder condition; perception of treatment benefit; the Medical Outcomes Study Short-Form 36 health survey; the King's Health Questionnaire; the OAB Questionnaire; and the Overall Treatment Effect scale.. The UPS correlated well with the patients' perception of bladder condition (correlation coefficients - 0.29 to - 0.46; all P < 0.001) and with the voiding diary variables, especially incontinence episodes (-0.30 to - 0.41) and pad usage (-0.25 to - 0.38; all P < 0.001). An improvement in UPS score at the end of treatment was consistently reflected by significant improvements among all voiding variables.. Urinary urgency is a central symptom of OAB and is particularly bothersome because of its unpredictability and consequent impact on daily life. The UPS is a valid scale by which urinary urgency can be assessed subjectively, and provides a useful tool for research into urinary urgency.

Topics: Aged; Benzhydryl Compounds; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Perception; Phenylpropanolamine; Quality of Life; Single-Blind Method; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

We report the results of the first 2 large randomized controlled trials designed to evaluate the efficacy and safety of tolterodine extended release in children 5 to 10 years old with symptoms of urinary urge incontinence suggestive of detrusor overactivity.. Two double-blind, placebo controlled trials were conducted sequentially. Children 5 to 10 years old with incontinence suggestive of detrusor overactivity (1 or more diurnal incontinence episodes per 24 hours) were randomized to tolterodine (2 mg daily) or placebo for 12 weeks. The primary end point was the change from baseline to week 12 in the number of incontinence episodes per week. Changes from baseline in the number of voids per 24 hours and volume of urine per void were also evaluated. Exploratory analyses were conducted to determine whether particular subsets of patients showed differential responses to treatment.. A total of 224 and 487 children (mean age 8 years) were randomized to placebo and tolterodine, respectively. Differences in the number of incontinence episodes per week, voids per 24 hours, and volume of urine per void between tolterodine and placebo did not reach statistical significance. This finding may be explained by a high placebo response and under dosage of tolterodine among children with greater body weight. Tolterodine was well tolerated.. Analysis of the primary efficacy outcome did not reveal a statistically significant effect of treatment. However, secondary analyses demonstrated that tolterodine was well tolerated among 5 to 10-year-old children with diurnal incontinence. Exploratory analyses also showed that children weighing 35 kg or less with detrusor overactivity characterized by incontinence and/or frequent voiding benefited most from tolterodine treatment, suggesting that a weight adjusted dosing regimen may be required for optimal response among older and heavier children.

Topics: Benzhydryl Compounds; Body Weight; Child; Child, Preschool; Circadian Rhythm; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Placebo Effect; Placebos; Safety; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Incontinence; Urination

To evaluate the effects of tolterodine and oxybutynin on visual accommodation, pupillary diameter, intraocular pressure and tear secretion in women with overactive bladder.. One hundred and four eyes from 52 consecutive female patients (age range: 22-60 years) with a urodynamic diagnosis of overactive bladder were prospectively investigated. Patients with a history of ocular disease or surgery were excluded. The subjects were randomly assigned to one of two groups: Group I received 2 mg tolterodine bid and Group II received 5 mg oxybutynin tid. All patients were evaluated at baseline (day 0) and after 1 month of treatment (day 28) by an ophthalmologist who was blinded to the medication. At each time point, a complete ophthalmic examination was performed and accommodation amplitude (AA), and pupillary diameter (PD) in dim and bright light were recorded. As well, tear secretion was assessed based on tear film break-up time and Schirmer I-test results. Statistical comparisons were made using the chi-square test, Student's t-test and Mann-Whitney U-test, as appropriate.. Twenty-eight patients (56 eyes) received tolterodine and 24 patients (48 eyes) received oxybutynin. The mean ages of the two groups were similar (P = 0.523). After 4 weeks of treatment, AA was significantly lower in the oxybutynin treated group (P = 0.003, 95% CI 0.15, 0.62) whereas there was no significant change in AA in the tolterodine treated group (P = 0.155, 95% CI -0.042, 0.86). At day 28, PD in dim light was significantly larger in the tolterodine treated group (P = 0.031, 95% CI -0.82, -0.06), whereas no significant change in PD in dim light was noted in the oxybutynin treated group (P = 0.330, 95% CI -0.38, 0.18). Neither group showed a significant change in PD in bright light values on day 28 (P > 0.05 for both). In each group, the differences from day 0 to day 28 for intraocular pressure, and Schirmer-I results were insignificant (P > 0.05 for all). Both groups had significantly shorter tear film break-up time after 1 month of therapy (P = 0.014 (95% CI 0.47, 3.81) and P = 0.02 (95% CI 1.14, 4.61) for the tolterodine and oxybutynin treated groups, respectively).. Four weeks of standard-dose oxybutynin treatment in women with overactive bladder decreases AA significantly, whereas the same duration of standard-dose tolterodine does not have this effect. However, tolterodine seemed to affect PD in dim light. One month of treatment with either of these anticholinergic drugs shortens tear film break-up time significantly. Concerning ocular side-effects, tolterodine seems to offer an advantage over oxybutynin because it does not affect AA, however, the shorter tear film break-up time with both agents suggests potential problems for patients who already have dry eye.

Topics: Accommodation, Ocular; Adult; Benzhydryl Compounds; Cresols; Eye Diseases; Humans; Intraocular Pressure; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Pupil; Single-Blind Method; Tears; Tolterodine Tartrate; Urinary Incontinence; Visual Acuity

To evaluate the long-term safety, tolerability and efficacy of extended-release (ER) tolterodine in Japanese patients completing 12-week treatment in a randomized, double-blind trial comparing tolterodine ER 4 mg once daily, oxybutynin 3 mg three times daily or placebo in patients with overactive bladder.. Of 293 Japanese patients completing the 12-week study, 188 continued in the open-label trial and received tolterodine ER 4 mg once daily for 12 months, irrespective of previous treatment. The primary objective was to assess the safety of tolterodine ER for up to 52 weeks of treatment and at post-treatment follow-up. Secondary endpoints included changes in micturition diary variables, patient perception of bladder condition and urgency and treatment benefit.. Overall, 77% of patients completed 12 months of open-label treatment. Tolterodine ER was well tolerated and the most common adverse event was dry mouth (33.5%). In general, there was no increase in adverse event frequency with long-term treatment compared with short-term treatment. The efficacy of tolterodine ER was maintained over the 12-month period. The complete analysis showed a median reduction in incontinence episodes/week (-92.9%; mean reduction, -77.2%), a mean reduction in micturitions/24 h (-21.3%) and a mean increase in volume voided per micturition (19.6%). Of patients completing the 12-month study, 78.6% reported improvement in patient perception of bladder condition, 52.4% reported improvement in perception of urgency and 89.7% reported treatment benefit.. Favorable safety, tolerability and efficacy of once-daily tolterodine ER was maintained over 12 months in a Japanese overactive bladder patient population.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Safety; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urodynamics

Propiverine and tolterodine were compared with respect to efficacy, tolerability and impact on the quality of life in the treatment of patients with idiopathic detrusor overactivity.. In a randomised, double-blind, multicentre clinical trial, patients with idiopathic detrusor overactivity were treated with 15 mg propiverine twice daily or 2mg tolterodine twice daily over a period of 28 days. The maximum cystometric capacity was determined at baseline and after 4 weeks of therapy. The difference of both values was used as the primary endpoint. Secondary endpoints were voided volume per micturition, evaluation of efficacy (by the investigator), tolerability, post void residual urine, and quality of life.. The mean maximum cystometric capacity increased significantly (p < 0.01) in both groups. The volume at first urge and the frequency/volume chart parameters also showed relevant improvements during treatment. 42/100 patients in the propiverine group and 43/102 in the tolterodine group experienced adverse events. The most common adverse event, dry mouth, occurred in 20 patients in the propiverine group and in 19 patients in the tolterodine group. The scores for the quality of life improved comparably in both groups.. The study demonstrates comparable efficacy, tolerability, and improvement in the quality of life of 15 mg propiverine twice-daily and 2mg tolterodine twice-daily in the treatment of the symptoms of idiopathic detrusor overactivity.

Topics: Adult; Benzhydryl Compounds; Benzilates; Calcium Channel Blockers; Cresols; Double-Blind Method; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Incontinence

To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome (OAB).. A prospective, double blind, double-dummy, two-arm, parallel-group, 12-week study was conducted to compare the efficacy and safety of solifenacin 5 or 10 mg and tolterodine extended release (ER) 4 mg once daily in OAB patients. After 4 weeks of treatment patients had the option to request a dose increase but were dummied throughout as approved product labelling only allowed an increase for those on solifenacin.. Solifenacin, with a flexible dosing regimen, showed greater efficacy to tolterodine in decreasing urgency episodes, incontinence, urge incontinence and pad usage and increasing the volume voided per micturition. More solifenacin treated patients became continent and reported improvements in perception of bladder condition assessments. The majority of side effects were mild to moderate in nature, and discontinuations were comparable and low in both groups.. Solifenacin, with a flexible dosing regimen, was found to be superior to tolterodine ER with respect to the majority of the efficacy variables.

Topics: Analysis of Variance; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

The incidence, severity and tolerability of dry mouth was compared in 790 women with overactive bladder who were treated with extended-release oxybutynin chloride 10 mg/day or extended-release tolterodine tartrate 4 mg/day for 12 weeks in a multicenter, double-blind, parallel-group study. Dry mouth was the most common adverse event associated with treatment, with an incidence rate of 28.1% in the oxybutynin group and 21.6% in the tolterodine group (P = 0.039). The majority of dry mouth events were mild in both treatment groups. Severe dry mouth occurred in 1.5% and 0.5% of patients in the oxybutynin and tolterodine groups, respectively (P = 0.173). Seven patients on extended-release oxybutynin and 4 patients on extended-release tolterodine discontinued treatment due to dry mouth (P = 0.380). The results of this analysis showed that dry mouth was common with both treatments, but most events were mild; there was no difference in the rate of severe dry mouth or in the rate of withdrawal due to dry mouth.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence; Xerostomia

To examine the efficacy and tolerability of antimuscarinic therapy in women with urge-predominant mixed incontinence.. This was a double-blind, randomized, placebo-controlled trial comprising 854 women with urge-predominant mixed incontinence, including urge incontinence (five or more episodes per week), urinary frequency (eight or more micturitions on average in 24 hours), and urgency in combination with stress incontinence. Women received 8 weeks of treatment with tolterodine tartrate extended-release (ER) 4 mg or placebo once daily. The outcome measures included urge incontinence episodes per week, stress incontinence episodes per week, micturition frequency per 24 hours, urgency episodes per 24 hours, volume voided per micturition, patient perception of bladder condition, and assessment of treatment benefit.. After 8 weeks, tolterodine ER produced a statistically significant decrease in the weekly urge incontinence episodes compared with placebo (-12.3 versus -8.0; P <0.0001). Other micturition variables improved significantly more with tolterodine ER. No difference was found between treatment groups regarding the change in the number of stress incontinence episodes. A significantly greater proportion of patients receiving tolterodine ER than those receiving placebo reported improvement in bladder condition (61% versus 46%; P <0.001) and treatment benefit (76% versus 55%; P <0.001). After 8 weeks, the tolterodine ER group had experienced statistically significant improvements compared with the placebo group in 9 of 10 quality-of-life domains. The frequency of adverse events was similar between treatment groups.. Tolterodine ER is an effective treatment of urge urinary incontinence, frequency, and urgency in women with concomitant stress urinary incontinence. The efficacy of tolterodine ER in reducing urge incontinence episodes was unaffected by the presence of stress incontinence. The results of this study support the first-line use of antimuscarinic therapy to treat the urge incontinence component of urge-predominant mixed incontinence.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Diuresis; Double-Blind Method; Female; Humans; Middle Aged; Muscarinic Antagonists; Patient Acceptance of Health Care; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urination; Xerostomia

Overactive bladder (OAB) has a significant impact on a patient's health-related quality of life (HRQoL). This study assessed the HRQoL of Japanese OAB patients following 12 weeks' treatment with tolterodine extended release (ER) or oxybutynin. A total of 293 patients with symptoms of OAB were randomized for treatment with tolterodine ER 4 mg once daily (n=114), oxybutynin 3 mg three times daily (n=122) or a placebo (n=57). Treatment efficacy and safety assessments were made over the 12-week period. HRQoL was assessed using the King's Health Questionnaire (KHQ). Patients receiving tolterodine ER or oxybutynin showed a significant (P<0.05) improvement in the Incontinence Impact, Role Limitations and most other KHQ domains compared with the placebo. These changes in HRQoL corresponded with significant (P<0.05) improvements in micturition diary variables for patients receiving tolterodine ER and oxybutynin compared with placebo. Our findings demonstrate that Japanese OAB patients receiving tolterodine ER or oxybutynin experienced overall improvement in their quality of life.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Health Status Indicators; Humans; Japan; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Urinary Incontinence

To compare tolterodine with oxybutynin and placebo in people with neurogenic detrusor overactivity.. Prospective, randomized, double-blind, crossover trial plus open-label comparative stage.. Ten participants with neurogenic detrusor overactivity due to spinal cord injury or multiple sclerosis who used intermittent catheterization.. Bladder capacity on cystometrogram, a 10-day record of catheterization volumes, number of incontinent episodes per day, and perceived dry mouth using a visual analog scale (VAS) were measured for the following: (a) a blinded comparison: tolterodine, 2 mg twice daily, vs placebo, twice daily; and (b) an unblinded comparison: oxybutynin vs tolterodine, each at self-selected doses (SSDs).. Tolterodine, 2 mg twice daily, was superior to placebo in enhancing catheterization volumes (P < 0.0005) and reducing incontinence (P < 0.001), but was comparable with placebo in cystometric bladder capacity. Efficacy of tolterodine SSD was comparable with oxybutynin SSD with regard to catheterization volumes, degree of incontinence, and cystometric bladder capacity. The side effect profile (dry mouth) was comparable between tolterodine, 2 mg twice daily, and placebo, but differed significantly when comparing tolterodine SSD with oxybutynin SSD (P < 0.05).. Tolterodine, when used at SSDs, is comparable with oxybutynin at SSDs in enhancing bladder volume and improving continence, but with less dry mouth. Tolterodine at the recommended dosage of 2 mg twice daily improves incontinence and bladder volumes compared with placebo, and without significant dry mouth. Larger doses of tolterodine may be needed to achieve best effect in this population, but further studies are required.

Topics: Adult; Benzhydryl Compounds; Cresols; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Multiple Sclerosis; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Spinal Cord Injuries; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence; Xerostomia

To compare the efficacy of tolterodine and oxybutynin in the treatment of specific, according to their urodynamic grade of severity, populations with overactive detrusor.. In this open, randomized, two-way crossover study 128 women with urodynamically confirmed, idiopathic detrusor overactivity were recruited. Patients were categorized in 4 grades of severity groups, according to the characteristics of the first overactive detrusor contraction during filling cystometrogram: high volume-low pressure (grade-group I), high volume-high pressure (grade-group II), low volume-low pressure (grade-group III) and low volume-high pressure (grade-group IV). The primary outcome measure was average volume of voided urine per micturition.. 107 patients successfully completed the study protocol and were included in the analyses: 40 in group IV, 36 in III, 25 in II and 6 in group I. In groups IV and III both oxybutynin and tolterodine significantly increased the average volume of voided urine per micturition but the differences between the drugs were not significant (p > 0.05). In group II neither of the drugs achieved significant changes in the outcome measure (p > 0.05).. Tolterodine and oxybutynin are clinically equipotent in treating detrusor overactivity in specific severity groups of patients, although urodynamic effects are somewhat different.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Cross-Over Studies; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence; Urodynamics

To assess a standardized and simple educational intervention in overactive bladder (OAB) patients to improve compliance with anticholinergic medication, increase the use of concomitant behavioral treatments, and improve patients' perception of bladder symptoms.. This is a 16-week open-label randomized trial of tolterodine combined with an education intervention for the experimental group versus tolterodine alone (no intervention) for the control group. The setting was in family medicine and urology clinics in Ontario. The participants were male and female adults with OAB symptoms. Both groups received tolterodine prescriptions. The intervention patients received printed information and an explanation about OAB, medication use, and behavioral treatments (kegel exercise, bladder stretching, fluid regulation). The primary outcomes were medication compliance and persistence at 16 weeks. Secondary outcomes were use of behavioral treatments and self-reported severity of symptoms.. More patients in the intervention group (experimental) purchased their prescriptions (p<0.05). Compliance rate was greater for the intervention group (39%), versus the control group (31%) at 16 weeks although the difference was not significant (p>0.05). Significantly more patients started and/or continued non-drug treatments in the intervention group (82%) compared to the control group (53%) (p<0.05). Furthermore, more patients in this group reported improvement in severity of bladder symptoms (p<0.05).. The simple education intervention resulted in a greater, but not significant, increase in compliance with medication compared to the control group. It also resulted in a significantly increased use of behavior modification therapies and better self-perception of treatment outcome.

Topics: Aged; Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Life Style; Male; Middle Aged; Muscarinic Antagonists; Patient Compliance; Patient Education as Topic; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To observe the efficacy of electrical stimulation in treatment of overactive bladder (OAB).. Patients (n = 60) with overactive bladder were randomly divided into 2 groups. Electrical stimulation group (n = 35) used an instrument for electrical stimulation through a special vagina or rectum probe transfer current (8-70 mA), for 20 min, qd, for 20-30 times. Medical group (n = 25) received oral tolterodine 2 mg, bid, for 2-4 weeks.. The total effective rate and cure rate were 74%, 37% in electrical stimulation group and 76%, 40% in medical group, respectively, showing no significant difference between two groups (P > 0.05). While patients' satisfactory rate was significantly higher in electrical stimulation group than in medical group (P < 0.05). Side effects were more commonly seen with tolterodine.. Electrical nerve stimulation is effective and safe for overactive bladder. Further studies are needed to show the long term efficacy and cost-effectiveness.

Topics: Adult; Aged; Benzhydryl Compounds; Constipation; Cresols; Electric Stimulation Therapy; Female; Humans; Middle Aged; Pelvic Floor; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination; Urination Disorders; Xerostomia

We compare the tolerability and efficacy of extended release oxybutynin chloride, and immediate release and long acting tolterodine tartrate in children with nonneurogenic diurnal urinary incontinence and symptoms of overactive bladder.. Children with a history of diurnal urinary incontinence were arbitrarily assigned to extended release oxybutynin, immediate release tolterodine or long acting tolterodine. The dose was titrated until effective (onset of complete diurnal urinary continence), maximal recommended dosage was achieved or bothersome anticholinergic side effects developed. An independent observer recorded the dose used, anticholinergic side effects and efficacy of therapy (incidence of urinary frequency, urgency, posturing and urinary incontinence).. The study included 86 girls and 46 boys. There were no statistically significant differences among the 3 treatment groups regarding the presence of peripheral or central nervous system anticholinergic side effects. Extended release oxybutynin and long acting tolterodine were significantly more effective at reducing daytime urinary incontinence than immediate release tolterodine (p <0.01 and 0 <0.05, respectively). Extended release oxybutynin was significantly more effective then long acting tolterodine for complete resolution of diurnal incontinence (p <0.05).. Extended release oxybutynin and long acting tolterodine are more effective than immediate release tolterodine in decreasing diurnal urinary incontinence. Extended release oxybutynin chloride is more effective than either immediate or long acting tolterodine for control of daytime urinary incontinence and urinary frequency.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Dosage Forms; Female; Humans; Male; Mandelic Acids; Phenylpropanolamine; Retrospective Studies; Tartrates; Tolterodine Tartrate; Urinary Incontinence

This study evaluated the efficacy and tolerability of new extended-release (ER) tolterodine for the treatment of overactive bladder in women. In this subpopulation analysis of a double-blind multicenter trial, 1235 female patients were randomized to oral therapy with tolterodine ER 4 mg once daily (n=417), tolterodine IR 2 mg twice daily (n=408) or placebo (n=410) for 12 weeks. Both formulations reduced the mean number of urge incontinence episodes per week (both P=0.001 vs placebo); tolterodine ER was more effective than tolterodine IR (P=0.036). Both formulations significantly improved all other micturition chart variables compared to placebo. Dry mouth was the most common adverse event. There were no safety concerns. Toltrodine ER 4 mg once daily is effective and well tolerated in the treatment of women with overactive bladder, and reduces urge incontinence episodes more than the existing IR twice-daily formulation.

Topics: Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

The therapy of mixed urinary incontinence is still discussed controversially. Surgical procedures were seen as a minor opinion in these cases, because the urge-symptoms remain stable or even become worse after incontinence-surgery. We here present a prospective-randomized double-blinded multi-center trial with Tolterodine extended-release 4 mg once daily in 410 female patients with mixed incontinence treated in Germany. After 8 weeks of treatment we saw a nearly 60% significant regression of the symptoms of mixed incontinence. Therefore the anticholinergic treatment with tolterodine extended-release of women is a successful treatment option in mixed incontinence.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Germany; Humans; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urodynamics

To examine the efficacy of tolterodine, an antimuscarinic agent with a bladder-selective profile, in patients with mixed incontinence (MI, stress and urge) compared with patients with urge incontinence (UI) alone.. The study included 239 patients with MI (urge predominating) and 755 with urge incontinence alone from a single-blind, multicentre trial of 1380 patients (80% female) with an overactive bladder. Those completing the trial were analysed 'per-protocol'. After a 7-day washout and a 3-day run-in to collect baseline information, patients were treated with tolterodine twice daily for 16 weeks. The two groups were compared for incontinence episodes/24 h, voiding frequency, nocturia episodes and pad usage after 16 weeks of treatment.. After 16 weeks the median changes from baseline for all voiding variables were statistically significant for the MI and the UI groups (P < 0.001), with no apparent significant between-group differences. The median percentage reduction in incontinence episodes from baseline was 67% for the MI and 75% for the UI groups (P = 0.39). 'Dry' rates for the MI and UI groups at the end of the study were 39% (66/171) and 44% (243/552), respectively, whilst 24% of patients in each group (MI 40/170; UI 130/551) achieved a voiding pattern of < 8 voids/24 h. 'Cure' rates for nocturia and the reduction in the number of patients not using pads used were also similar between the groups.. Tolterodine is as effective in reducing leakage and other symptoms of an overactive bladder in patients with MI as it is in patients with UI alone.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Single-Blind Method; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urination

To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder.. 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.. 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.. 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.

Topics: Administration, Oral; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Diarrhea; Double-Blind Method; Female; Headache; Humans; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Salivation; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Tract Infections; Urination

To evaluate the effect of once-daily, extended-release tolterodine on urinary urgency in patients with overactive bladder.. Patients with urinary frequency (eight or more micturitions per 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral treatment with tolterodine extended release 4 mg once daily (n=398) or placebo (n=374) for 12 weeks. Efficacy was assessed by use of patient perception evaluations.. The results presented are a secondary analysis of this double-blind, placebo-controlled study. Of patients treated with tolterodine extended release, 44% reported improved urgency symptoms (compared with 32% for placebo), and 62% reported improved bladder symptoms (placebo, 48%) (both P<.001 compared with placebo). The odds of reducing urgency and improving bladder symptoms were 1.68 and 1.78 times greater, respectively, for patients in the tolterodine extended release group than for patients receiving placebo. In response to urgency, there was a more than six-fold increase in the proportion of patients able to finish a task before voiding in the tolterodine extended release group. The proportion of patients unable to hold urine upon experiencing urgency was also decreased by 58% with tolterodine, compared with 32% with placebo (P<.001). The proportion of patients reporting "much benefit" from treatment was greater for tolterodine extended release than for placebo (43% versus 24%; P<.001). The only adverse events with an incidence of greater than 5% were dry mouth, headache, and constipation, with only dry mouth markedly more frequent with tolterodine than with placebo.. Tolterodine extended release has demonstrable efficacy in reducing the severity of urinary urgency and is associated with improvements in overactive bladder symptoms that are meaningful to patients.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Confidence Intervals; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Odds Ratio; Patient Satisfaction; Phenylpropanolamine; Probability; Reference Values; Severity of Illness Index; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urinary Incontinence; Urination Disorders

Oxybutynin binds to the M(3) muscarinic receptors on the detrusor muscle of the bladder, preventing acetylcholinergic activation and relaxing the muscle. The transdermal system delivers oxybutynin over a 3- to 4-day period after application to intact skin. Peak plasma concentrations of oxybutynin and the major active metabolite, N-desethyloxybutynin, are reached 24 - 48 hours after a single application and therapeutic concentrations are maintained throughout the dosage interval. In a large, randomised, double-blind trial, transdermal oxybutynin 3.9 mg/day significantly decreased the median number of incontinence episodes per week compared with placebo (-19 vs -15, p = 0.0165) in patients with overactive bladder. In addition, the micturition frequency was reduced and average voided volume was increased by transdermal oxybutynin treatment. Significant reductions in incontinence episodes following transdermal oxybutynin treatment were also observed in two further studies and the clinical efficacy was similar to that of oral tolterodine or oral oxybutynin. Transdermal oxybutynin was well tolerated in clinical trials. Application site reactions were the most common adverse effect; however, the majority were mild to moderate in severity. Adverse events associated with anticholinergic drugs (e.g. dry mouth) were less frequently reported in patients treated with transdermal oxybutynin than in those receiving orally administered oxybutynin or tolterodine.

Topics: Administration, Cutaneous; Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Exanthema; Humans; Mandelic Acids; Middle Aged; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

To compare extended-release (ER) tolterodine and immediate-release (IR) oxybutynin with placebo in Japanese and Korean patients with an overactive bladder (OAB).. Men and women aged >or= 20 years with symptoms of urinary urgency, urinary frequency (>or= 8 micturitions/24 h), urge incontinence (>or= 5 episodes/week) and symptoms of OAB for >or= 6 months were randomized to double-blind treatment with tolterodine ER 4 mg once daily, oxybutynin IR 3 mg three times daily or placebo for 12 weeks. Efficacy assessments included changes from baseline in numbers of incontinence episodes per week, voids/24 h and mean volume voided/void. Patient perceptions of bladder condition, urgency and treatment benefit were also assessed.. In all, 608 patients were randomized to treatment with tolterodine (240), oxybutynin (246) or placebo (122). More patients prematurely withdrew on oxybutynin (23%) than with tolterodine (10.4%) or placebo (16.4%). After 12 weeks of treatment, the median number of incontinence episodes/week was reduced significantly more in the tolterodine (79%; P= 0.0027) and oxybutynin groups (76.5%; P= 0.0168) than on placebo (46.4%). There were also significantly greater improvements in the number of voids/24 h and volume voided/void with tolterodine and oxybutynin than with placebo. More patients in the tolterodine and oxybutynin than in the placebo groups reported improvements in perceived bladder condition, ability to hold urine and treatment benefit. Patients treated with oxybutynin reported more adverse events than those treated with tolterodine or placebo. Dry mouth was significantly more common with oxybutynin than with tolterodine (53.7% vs. 33.5%; P < 0.001), and occurred in 9.8% of placebo patients.. Tolterodine ER has similar efficacy but is better tolerated than oxybutynin IR in Japanese and Korean patients with OAB.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Diseases; Urinary Incontinence; Urination

Objective To compare the tolerability and clinical efficacy of tolterodine and oxybutynin in the treatment of Hong Kong Chinese women with an overactive bladder. Patients and methods A randomized controlled trial was conducted at two urogynaecology centres in Hong Kong. In all, 106 women with urodynamically confirmed detrusor instability were recruited. Baseline severity assessments included a visual analogue scale (VAS), urinary diary and urinary pad-test. The women were randomized to receive either oral tolterodine 2 mg or oxybutynin 5 mg twice daily for 10 weeks. Treatment responses were assessed at 4 and 10 weeks using the VAS and urinary diary. Treatment tolerability was assessed at baseline, 4 and 10 weeks using the Xerostomia Questionnaire. A urinary pad-test was repeated at 10 weeks. Results The perceived change from baseline VAS was better in the tolterodine than the oxybutynin group after 10 weeks of treatment (per-protocol analysis, P = 0.043). The two drugs were effective in reducing the symptoms of frequency (P < 0.001). Tolterodine was significantly better than oxybutynin in reducing urinary leakage (urinary pad-test; median change - 5.00 g vs 0 g, P = 0.019). Both drugs caused a significant worsening of dry mouth (overall dryness, P < 0.005; discomfort, P < 0.005; sleep, P = 0.021; speaking, P = 0.045; swallowing, P = 0.004; and liquid consumption, P = 0.017). Conclusions Both oxybutynin and tolterodine were effective in ameliorating the severity of the symptoms of detrusor instability. Tolterodine was better than oxybutynin in both subjective and objective outcome measures, but both drugs caused similar worsening of dry mouth that may limit the tolerability of these medications.

Topics: Administration, Oral; Adult; Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Mandelic Acids; Middle Aged; Muscarinic Agonists; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients.. A 12-week double-blind, placebo-controlled clinical trial.. An international study conducted at 167 medical centers.. One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency.. Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks.. Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older.. Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87).. The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

This double-blind, multicenter study compared the efficacy and tolerability of tolterodine (Pharmacia, Los Angeles, USA) with that of oxybutynin (Alza, Palo Alto, USA) in Asian patients with overactive bladder.. Two-hundred-and-twenty-eight adults with overactive bladder symptoms were randomized to receive tolterodine 2 mg twice daily (bid) (n = 112) or oxybutynin 5 mg bid (n = 116). After 8 weeks' treatment, changes in micturition diary variables, patients' perception of treatment benefit, and tolerability endpoints were determined.. The mean (+/- SD) number of micturitions/24 h decreased by 2.6 +/- 2.9 (-21%) with tolterodine and 1.8 +/- 4.2 (-15%) with oxybutynin (both P = 0.0001 vs baseline). The mean number of incontinence episodes/24 h decreased by 2.2 +/- 2.3 (-85%) in the tolterodine group and by 1.4 +/- 1.8 (-58%) in the oxybutynin group (both P = 0.0001 vs baseline). Patient perception of treatment benefit was over 70% in each treatment group. Adverse events were significantly lower in the tolterodine group compared with oxybutynin-treated patients (55% vs 82%; P = 0.001). Dry mouth was reported by significantly fewer patients on tolterodine, compared with oxybutynin (35% vs 63%; P = 0.001) and withdrawals due to adverse events were lower in the tolterodine group than with those treated with oxybutynin (10% vs 16%). There were no safety concerns.. Tolterodine 2 mg bid is equally or more effective than oxybutynin 5 mg bid in the treatment of Asian patients with overactive bladder, and shows significantly better tolerability. This may enhance compliance during long-term treatment.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination

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.. 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.. 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.. 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.

Topics: Administration, Oral; Adult; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Urination Disorders

To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder.. Thirty-three children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and symptoms of urgency, frequency and/or urge incontinence were enrolled in an open, dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n = 11), 1 mg (n = 10) or 2 mg (n = 12) twice daily for 14 days. The primary safety endpoint was the change in residual urinary volume, as determined by ultrasonography. In addition, voiding diary variables (frequency and incontinence episodes) and pharmacokinetics were evaluated. Other safety endpoints included laboratory variables, electrocardiogram recordings and reported adverse events.. There were no safety concerns in terms of the change in residual urinary volume for any of the three dosage groups; values were comparable with baseline after 2 weeks of treatment for all three dosages. Adverse events were reported by 20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events were not considered to be drug-related; of the 13 possibly related events, 10 occurred in those taking 2 mg. Headache was the most commonly reported adverse event. No serious adverse events were reported and there were no general safety concerns. There was an improvement in voiding diary variables in all treatment groups after 2 weeks of treatment, although the efficacy was greatest in those taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose linearity over the range 0.5-2 mg.. The results support the use of 1 mg twice daily as the optimal dose of tolterodine for treating children aged 5-10 years with an overactive bladder.

Topics: Administration, Oral; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Dose-Response Relationship, Drug; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder.. Randomized, double-blind, placebo-controlled, parallel-group, multinational, phase III study.. Incontinence, older care, urological, and urogynecological clinics in the United Kingdom, France, and the Republic of Ireland.. One hundred and seventy-seven older patients (age > or =65 years) with symptoms of urinary urgency, increased frequency of micturition (> or =8 micturitions/24 hours), and/or urge incontinence (> or =1 episode/24 hours).. Tolterodine 1 mg or 2 mg twice daily (bid), or placebo, for 4 weeks.. Safety and tolerability were evaluated through spontaneously reported adverse events, electrocardiogram, and blood pressure measurements. Efficacy was assessed using micturition diary variables: mean change from baseline in frequency of micturition and number of incontinence episodes/24 hours.. The mean age of the patient population was 75 years. Overall, > or =87% of patients completed the study. Neither dosage of tolterodine was associated with serious drug-related adverse events during the study. No cardiac arrythmogenic events were noted. Dry mouth (mild to moderate intensity) was the most common adverse event in both the placebo and tolterodine treatment groups. Three percent of patients in the tolterodine 2 mg bid group discontinued treatment because of dry mouth, compared with 2% of placebo-treated patients. Compared with placebo, statistically significant decreases in micturition frequency were apparent in both tolterodine treatment groups. Furthermore, patients treated with tolterodine 2 mg bid had statistically significant decreases in urge incontinence episodes/24 hours and increases in volume voided per micturition compared with placebo.. Tolterodine (taken for 4 weeks) is safe and shows efficacy, particularly at a dosage of 2 mg bid, in the treatment of older patients with urinary symptoms attributable to overactive bladder.

Topics: Age Factors; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Monitoring; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Placebos; Safety; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination Disorders; Xerostomia

To evaluate the efficacy, safety and tolerability of tolterodine compared to placebo in patients with an overactive bladder.. A double-blind, multi-centre phase III study in France and Belgium 251 patients with overactive bladder symptoms, and urodynamically verified detrusor overactivity, were randomised to receive 4-week treatment with either placebo or tolterodine 1 or 2mg twice daily (bd). Efficacy was evaluated from patient micturition diaries. Safety and tolerability endpoints were also evaluated.. After 4-week treatment, the number of incontinence episodes/24h decreased significantly relative to placebo in the tolterodine 1 and 2 mgbd groups (P=0.045 and P=0.0089, respectively). Both dosages of tolterodine increased volume voided per micturition compared with placebo (P=0.055 and P=0.056, respectively), although significant decreases in micturition frequency were not apparent. Tolterodine was safe and well tolerated, few patients were withdrawn due to adverse events. Dry mouth, mainly of mild-to-moderate intensity, was the most common adverse event. No clinically relevant changes in blood pressure or laboratory safety variables were reported.. Tolterodine is effective, safe and well tolerated for the treatment of symptoms of an overactive bladder, particularly urge incontinence.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Belgium; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; France; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Placebos; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Urination; Urine

We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity.. In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects.. After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events.. Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

This is a prospective study of 28 patients who had urinary frequency (>8 times/day) and either urgency or urge incontinence (>1 time/day). After a 2-week run-in period (visit 1), the patients were started on tolterodine 1 mg twice a day (bid) (visit 2). They were followed at 4 and 8 weeks (visits 3 and 4). The patients were contacted by telephone 1 week after visit 2. Tolterodine was increased to 2 mg bid if the patient had incomplete improvement at either the initial phone call or during visit 3. Evaluation criteria were daily micturition charts including urinary frequency, nocturia, leakage episodes, average urine volume per day, and average voided volume. Tolterodine was well tolerated without side effects in 20 (80%) of 28 patients. Eight patients (20%) dropped out after enrollment because of side effects in 3, no improvement in 2, and missing visits (>1) in 3. Drug dosage in the 20 patients who tolerated tolterodine was 1 mg bid in 3 and 2 mg bid in 17 (85%). According to micturition charts, urinary frequency, nocturia, and leakage episodes decreased significantly after tolterodine treatment, whereas average urine volume per day and average voided volume did not change significantly. There were no electrocardiographic or biochemical abnormalities due to tolterodine treatment. Mean follow-up was 9.4 months. All 20 patients who tolerated tolterodine continue to take the medication without significant side effects. We conclude that tolterodine is well tolerated and effective for overactive bladders. Two milligrams bid is the dosage preferred by the majority of patients and the onset of action is seen within 1 week of treatment. Long-term compliance and efficacy are excellent, with no dropout in >9 months of follow-up.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Surveys and Questionnaires; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence; Urodynamics

This study compared the clinical efficacy (determined from micturition diaries) and safety of 12 weeks' treatment with either tolterodine 2 mg twice daily, oxybutynin 5 mg three times daily or placebo in patients with an overactive bladder. A total of 277 patients were randomized and treated at 25 centers. Both tolterodine and oxybutynin significantly increased volume voided/micturition compared to placebo. Both treatment groups evoked greater decreases in micturitions per 24 hours and incontinence episodes per 24 hours compared to placebo; however, only tolterodine was significantly better than placebo in reducing micturition frequency. Tolterodine and oxybutynin were equivalent in their effectiveness. Tolterodine was significantly better tolerated than oxybutynin when adverse events (particularly frequency and intensity of dry mouth), dose reduction and patient withdrawals were considered. Oxybutynin is an effective drug whose frequent adverse effects limit its clinical usefulness. Tolterodine has equivalent efficacy to oxybutynin, but with less severe adverse effects. This will allow patients to receive more effective treatment for their condition, with better compliance.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination

Tolterodine is a new competitive muscarinic receptor antagonist developed for the treatment of the unstable bladder. A total of 242 patients were enrolled in a multicenter, multinational, randomized, double-blind, placebo-controlled study conducted over a period of 4 weeks in patients with detrusor overactivity and symptoms of frequency, urgency, and urge incontinence. The objective of the study was to compare the efficacy and safety of tolterodine given at 1 or 2 mg b.i.d. versus placebo. At week 4 a statistically significant increase in the volume at first contraction (p = 0.030) and maximal cystometric capacity (p = 0.034) was only in the tolterodine 2 mg b.i.d. group. Tolterodine was safe and generally well tolerated. The incidence of dry mouth, as the most commonly reported adverse event, was only 9% and of mild to moderate intensity.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Placebos; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Urodynamics

To examine the safety, efficacy, and tolerability of tolterodine in four randomized, double-blind, parallel, multicenter, 12-week studies of patients with overactive bladder.. Two of the four studies compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily) and placebo, one study compared tolterodine (2 mg twice daily) to oxybutynin (5 mg three times daily), and one study compared two dosages of tolterodine (1 and 2 mg twice daily) to placebo. Efficacy was determined from micturition diaries and patient perception of their bladder condition. Safety and tolerability were assessed from adverse events and laboratory measures.. A total of 1,120 patients were randomized and treated at 134 centers. For the primary efficacy variable, the number of micturitions/24 hours, pooled results showed a significant decrease from baseline for the 1 mg tolterodine (P < 0.001), 2 mg tolterodine (P < 0.001), and 5 mg oxybutynin (P < 0.01) groups, compared to placebo. Both tolterodine doses and oxybutynin significantly decreased incontinence episodes/24 hours and significantly increased volume voided/micturition, compared to placebo. Tolterodine at a dose of 2 mg twice daily and 5 mg oxybutynin twice daily were significantly more effective in improving patient perception of bladder condition than placebo. Tolterodine at a dose of 2 mg and 5 mg oxybutynin were equivalent in their effectiveness. Tolterodine at doses of 1 mg and 2 mg were tolerated significantly better than oxybutynin when adverse events, dry mouth (both frequency and intensity), dose reductions, and patient withdrawals were considered.. Although oxybutynin is highly effective, its clinical utility is limited by systemic side effects that lead to frequent discontinuation of treatment or dose reductions. Patients receiving tolterodine should not experience these limitations and instead will get safe and long-term effective treatment for their condition.

Topics: Adult; Analysis of Variance; Benzhydryl Compounds; Chi-Square Distribution; Cholinergic Antagonists; Confidence Intervals; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Statistics, Nonparametric; Time Factors; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Incontinence; Urination

To assess the cost-effectiveness of mirabegron 50 mg relative to tolterodine extended release 4 mg for the treatment of overactive bladder if used as the first-line treatment in Japan.. A Markov model was developed to simulate the cost-effectiveness of the mirabegron first-line treatment (and tolterodine second-line) versus tolterodine first-line treatment (and mirabegron second-line) taken for 5 years from the randomized European-Australian study (SCORPIO trial) and single technology appraisal assessment report by the National Institute for Health and Care Excellence. The incremental cost-effectiveness ratio was calculated with utility value by quality-adjusted life year with cost using the medical fee and the drug price tariff in 2016. For the study of transition of treatment status, our analytical model was established. The transition probabilities of severity states were calculated based on the probabilities for the mean numbers of incontinence episodes/day and micturition episodes/day in mirabegron-treated and tolterodine-treated patients in the single technology appraisal assessment report.. The 5-year expected effect per patient was 3.860 quality-adjusted life years for first-line mirabegron and 3.839 quality-adjusted life years for first-line tolterodine. The 5-year expected cost per patient was ¥526 191 for first-line mirabegron, and ¥472 390 for first-line tolterodine. The incremental cost-effectiveness ratio was ¥2 565 927/quality-adjusted life year. This value was below the willingness-to-pay threshold of ¥5 million/quality-adjusted life year. In more severe states, the incremental cost-effectiveness ratio exceeded ¥5 million.. First-line mirabegron appears to be more cost-effective than first-line tolterodine. In patients with severe symptoms, first-line mirabegron is not economically preferable.

Topics: Acetanilides; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Costs; Humans; Japan; Markov Chains; Muscarinic Antagonists; Quality of Life; Severity of Illness Index; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To investigate the characteristics of autonomic function and arterial stiffness of OAB women, their relations with urodynamic parameters, and the impact of antimuscarinics on the above parameters.. A total of 85 OAB women and another 65 women without OAB were selected. Forty-two OAB women who enrolled before March 2009 were treated with tolterodine for 12 weeks, and another 43 OAB women who enrolled thereafter were treated with solifenacin.. The differences of the heart rate variability, cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI) between OAB and asymptomatic women, and their changes after 12 weeks' antimuscarinics for OAB women.. OAB women had higher low frequency/high frequency ratios (LF/HF) (OAB: 1.5±1.1 vs. the control: 1.1±0.7, P=0.04). Nonetheless, CAVI and ABI did not differ between OAB and the control group. The square root of the mean squared differences of successive NN intervals (RMSSD) is associated with nocturia (Spearman's ρ=0.23, P=0.049), LF is associated with urgency episodes (Spearman's ρ=0.28, P=0.01), and maximum urethral closure pressure is negatively associated with CAVI (Spearman's ρ=-0.26, P=0.02). After 12 weeks' treatment, a decrease of RMSSD, HF, CAVI and an increase of LF/HF were found in the tolterodine group but not in the solifenacin group.. OAB women have higher severity of autonomic dysfunction with sympathetic predominance. Tolterodine may improve arterial stiffness but may deteriorate autonomic dysfunction to more sympathetic predominance. Thus, tolteridine should be used for OAB with caution in women with preexisting symptoms of autonomic dysfunction.

Topics: Adult; Ankle Brachial Index; Blood Pressure; Electrocardiography, Ambulatory; Female; Heart Rate; Humans; Middle Aged; Muscarinic Antagonists; Nocturia; Pressure; Solifenacin Succinate; Tolterodine Tartrate; Urethra; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urodynamics; Vascular Stiffness

To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the U.K. National Health Service (NHS).. A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a U.K. database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios.. Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs. 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY.. Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Topics: Benzhydryl Compounds; Cohort Studies; Cost-Benefit Analysis; Cresols; Humans; Incontinence Pads; Mandelic Acids; Markov Chains; Medication Adherence; Models, Economic; Muscarinic Antagonists; Patient Dropouts; Phenylpropanolamine; Quality-Adjusted Life Years; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; United Kingdom; Urinary Bladder, Overactive; Urinary Incontinence

To present a case of syndrome of inappropriate antidiuretic hormone (SIADH) associated with the use of tolterodine.. An acute-care unit at a university hospital with a comprehensive program for elders.. In this case report, we present a 99-year-old female who was admitted to our unit for suspected gastrointestinal bleeding who subsequently developed hyponatremia. After the initiation of tolterodine for urinary incontinence, the patient's sodium dropped to 121 mEq/L (from a usual baseline that ranged between 128 mEq/L and 134 mEq/L). Laboratory and urinary findings revealed a serum osmolality of 220 mOsm/kg, a urinary osmolality of 340 mOsm/kg, and a urinary sodium of 101 mmol/L, suggesting a euvolemic hyponatremic state consistent with SIADH. Tolterodine therapy was promptly discontinued, and patient sodium levels normalized.. Although the etiology of SIADH is often obscure and multifactorial, clinicians should be aware that it is a major cause of hyponatremia among hospitalized elderly patients, and drug therapies must always be evaluated to prevent further complications.

Topics: Aged, 80 and over; Benzhydryl Compounds; Cresols; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To investigate the pharmacoeconomic performance of treatment with solifenacin, a new antimuscarinic with selectivity for the bladder, when compared to tolterodine and placebo, in Italian patients with overactive bladder (OAB).. The evaluation was performed using a Markov model. The time horizon of the simulation was 52 weeks, with 1-week cycles. The model simulated outcomes and costs of the treatment with solifenacin (5 mg/day), tolterodine ER (4 mg/day) and no treatment in a cohort representative of the Italian population with OAB. The analysis was conducted mainly from the perspective of the patient, since drugs for the treatment of OAB are not included in the Italian reimbursement list. A supplementary scenario explored the consequences of a hypothetical reimbursement decision by the Italian Health Service to reimburse half of the current retail price in incontinent and responding OAB patients only.. Both treatments produced a reduction in symptoms and improvement in patients' quality of life, with an cost increase of about euro 540-640/patient/year with solifenacin and euro 680-780/patient/year with tolterodine. In a cost/utility analysis, solifenacin dominated tolterodine as it resulted in both more effective and less costly treatment; the cost/utility ratio with respect to no treatment was in the range euro 7,600-18,600/Quality-adjusted life year. The overall expenditure of the hypothesised reimbursement decision was estimated to be about 23 million euros, with a cost/utility ratio of about euro 600-2,400/Quality-adjusted life year, indicating an efficient allocation of health resources.. While both tolterodine and solifenacin appear to be cost/effective in Italy, the latter has proven to be superior.

Topics: Benzhydryl Compounds; Computer Simulation; Cost-Benefit Analysis; Cresols; Humans; Italy; Markov Chains; Muscarinic Antagonists; Pharmacogenetics; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Female; Humans; Muscarinic Antagonists; Orgasm; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Female; Humans; Muscarinic Antagonists; Orgasm; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

To understand the pathophysiological mechanism of incontinence during orgasm and to compare women affected by symptomatic detrusor overactivity (DO) with and without incontinence at orgasm in terms of efficacy of antimuscarinic treatment.. All consecutive sexually active women with incontinence during intercourse were prospectively included and divided into two groups: women with coital incontinence at orgasm or at penetration. The two forms of coital incontinence were correlated to the urodynamic finding of DO. Women complaining of overactive bladder (OAB) symptoms, with urinary incontinence at orgasm and urodynamically proven DO (cases), were prescribed tolterodine 4 mg extended release for at least 12 wk. The cases were compared in terms of efficacy of treatment on OAB symptoms to consecutive patients with symptomatic DO without coital incontinence (control group).. Among the 1133 women who underwent urodynamic testings during the study period, 132 patients were eligible for final analysis. A significant difference in DO was observed in women with incontinence at orgasm (34 of 49; 69.4%) compared with women with incontinence during penetration (24 of 83; 28.9%) (p<0.0001). The 34 women with incontinence at orgasm associated with DO were given antimuscarinics treatment and were compared with 53 controls. Fourteen of 34 (41.2%) and 9 of 53 (17%) women did not respond to antimuscarinics in the cases and in the control group, respectively (p=0.023).. Incontinence at orgasm is associated with DO in the majority of cases. This is the first study showing an inferior efficacy of antimuscarinic treatment in women with DO complaining of incontinence at orgasm.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Female; Humans; Middle Aged; Muscarinic Antagonists; Orgasm; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Young Adult

To determine the cognitive and functional consequences of dual use of cholinesterase inhibitors (ChIs) and the bladder anticholinergics oxybutynin or tolterodine.. Prospective cohort study.. Nursing homes (NHs) in the state of Indiana.. Three thousand five hundred thirty-six Medicaid-eligible NH residents aged 65 and older taking a ChI between January 1, 2003, and December 31, 2004. Residents were excluded if they were taking an anticholinergic other than oxybutynin or tolterodine.. Indiana Medicaid claims data were merged with data from the Minimum Data Set (MDS). Repeated-measures analyses were performed to assess the effects of dual therapy on change in cognitive function measured using the MDS Cognition Scale (MDS-COGS; scored 0-10) and change in activity of daily living (ADL) function using the seven ADL items in the MDS (scored 0-28). Potential covariates included age, sex, race, number of medications, and Charlson Comorbidity Index score.. Three hundred seventy-six (10.6%) residents were prescribed oxybutynin or tolterodine concomitantly with a ChI. In residents in the top quartile of ADL function, ADL function declined an average of 1.08 points per quarter when not taking bladder anticholinergics (ChI alone), compared with 1.62 points per quarter when taking dual therapy, a 50% greater rate in quarterly decline in ADL function (P=.01). There was no excess decline attributable to dual therapy in MDS-COGS scores or in ADL function for residents who started out with lower functioning.. In higher-functioning NH residents, dual use of ChIs and bladder anticholinergics may result in greater rates of functional decline than use of ChIs alone. The MDS-COGS may not be sensitive enough to detect differences in cognition due to dual use.

Topics: Activities of Daily Living; Aged; Alzheimer Disease; Benzhydryl Compounds; Cholinergic Antagonists; Cholinesterase Inhibitors; Cognition Disorders; Cohort Studies; Cresols; Drug Interactions; Drug Therapy, Combination; Female; Follow-Up Studies; Homes for the Aged; Humans; Male; Mandelic Acids; Neuropsychological Tests; Nursing Homes; Phenylpropanolamine; Prospective Studies; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Urinary symptoms in Parkinson's disease (PD) are minor but disabling. We have analyzed correlation of urinary symptoms with motor symptoms, duration and severity of PD and urodynamic abnormalities observed. Response to treatment with tolterodine was also assessed.. PD male patients with a score in IPSS questionnaire over 7 and female patients with a score in IU-4 scale over 5 were included in the study. Intensity of neurological symptoms (UPDRS score), seriousness of PD (Hohen-Yahr stage), urodynamic parameters, and urinary sediment were analyzed in each patient. Abdominal ultrasonography and rectal examination were performed in males to exclude obstructive prostatic pathology. Patients without evidence of urinary flow obstruction were treated with tolterodine.. Three out of the 19 patients were excluded because of abnormal urinary sediment and the rest (n = 16) were included. Urinary symptoms correlated with rigidity severity (p < 0.01) and years of evolution of PD (p < 0.01). Rigidity (p < 0.01) was the neurological sign with the highest UPDRS motor scale score. Overactive bladder was present in 13 cases (81.2%) and 4 of them had urinary flow obstruction. Clinical improvement in nine patients treated with tolterodine was mild (33%).. Urinary symptoms correlate with rigidity severity and with years of evolution of PD. The use of both the urinary questionnaire and urodynamic study allow us to identify the type of bladder dysfunction and select the patients who would benefit the most from anticholinergics. Tolterodine reduced miccional urgency and frequency in PD, but was ineffective on urinary incontinence.

Topics: Aged; Benzhydryl Compounds; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Parkinson Disease; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urodynamics

Topics: Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Muscarinic Antagonists; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Syndrome; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity.. Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group).. Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case.. This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.

Topics: Administration, Intravesical; Analysis of Variance; Animals; Benzhydryl Compounds; Cresols; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Tolterodine Tartrate; Urinary Bladder; Urinary Incontinence

Tolterodine is an effective agent used to treat symptoms of overactive bladder. It is well tolerated and its selectivity for the bladder results in less side effects overall compared to many other agents. Many patients in New Zealand with symptoms of overactive bladder do not have access to tolterodine due to restrictions on its funding by PHARMAC. Alternative treatments are not as well tolerated and are less clinically useful. This leaves many patients vulnerable to significant compromise of their quality of life.

Topics: Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Drug Administration Schedule; Drug Evaluation; Government Regulation; Humans; Muscarinic Antagonists; New Zealand; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Topics: Analysis of Variance; Benzhydryl Compounds; Controlled Clinical Trials as Topic; Cresols; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence

Topics: Adult; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To assess the clinical efficacy of tolterodine prescribed to children with non-neurogenic daytime urinary incontinence secondary to overactive bladder who had previously failed to improve with oral oxybutynin treatment and its relation to the side-effect profile and compliance status.. We evaluated 92 children presenting with daytime wetting, with or without nocturnal enuresis, who were receiving oral oxybutynin treatment. Children with chronic urinary tract infections, a neurologic lesion, an anatomic abnormality of lower urinary tract, voiding abnormality, and less than 1 year of oxybutynin treatment were excluded. Of the remaining 41 children (mean age 7.2 years, range 5 to 14 years), 30 agreed to switch to tolterodine and 11 continued receiving oxybutynin. Anticholinergic side effects, compliance, and clinical efficacy were assessed in the follow-up.. Of the 30 patients who switched to tolterodine, a complete response was in 18 patients (60%), partial improvement in 11 (37%), and no improvement in 1 (3%) after a mean of 14.4 months (range 12 to 16 months) of oxybutynin treatment. The anticholinergic side-effect score was 7.2, 9.3, and 11, respectively, for those with a complete response, partial improvement, and no improvement in the compliant group. The noncompliant group had the greatest side-effect score (16.9). The fairly compliant group had a side-effect score of 12.3. After a mean of 7.1 months (range 6 to 9 months) of tolterodine use, a complete response was reported in 24 patients and partial improvement in 5 (17%). In 1 patient, treatment failed completely. However, his side-effect score decreased from 11 to 2. All tolterodine users were compliant with treatment.. The results of this study in children with non-neurogenic daytime urinary incontinence have shown that tolterodine may increase the efficacy of pharmacotherapy, particularly in patients noncompliant to oxybutynin. Additional investigation of the anticholinergic side-effect scores and compliance tables is required to improve the clinical results of pharmacotherapy in incontinence due to overactive bladder in children.

Topics: Adolescent; Behavior Therapy; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Combined Modality Therapy; Cresols; Drug Evaluation; Drug Resistance; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Topics: Benzhydryl Compounds; Child; Child, Preschool; Cresols; Delayed-Action Preparations; Humans; Muscarinic Antagonists; Phenylpropanolamine; Placebo Effect; Placebos; Tolterodine Tartrate; Urinary Incontinence; Urodynamics

Topics: Benzhydryl Compounds; Cresols; Doxazosin; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urinary Incontinence

Authors evaluated the cognitive, neurophysiologic, and behavioral effects of incontinence medications in patients with Alzheimer disease (AD).. Nine patients were evaluated, both on and off incontinence medication, for cognitive status, neuropsychiatric status, activities of daily living, and serum anticholinergic level. Caregivers were interviewed to evaluate behavioral status and caregiver burden.. Patients showed better performance on specific measures of cognition and behavior when not taking medication for incontinence. A significant, inverse correlation was found between mental status and anticholinergic level.. Although the sample size was small, the findings suggest that, in patients with AD, incontinence medications with anticholinergic properties may have detrimental effects on mental status and behavior.

Topics: Activities of Daily Living; Alzheimer Disease; Benzhydryl Compounds; Caregivers; Cholinergic Antagonists; Cognition Disorders; Cresols; Cross-Over Studies; Humans; Memory Disorders; Mental Disorders; Muscarinic Antagonists; Neuropsychological Tests; Phenylpropanolamine; Psychometrics; Single-Blind Method; Surveys and Questionnaires; Tolterodine Tartrate; Urinary Incontinence; Wakefulness

Topics: Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urodynamics

Topics: Adrenergic Uptake Inhibitors; Benzhydryl Compounds; Controlled Clinical Trials as Topic; Cresols; Duloxetine Hydrochloride; Female; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Selective Serotonin Reuptake Inhibitors; Thiophenes; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urinary Incontinence, Stress; Urodynamics

Two thirds of patients with overactive bladder (OAB) are continent, but our knowledge on the treatment of the syndrome is largely based on studies with incontinent patients. Therefore, we have explored baseline symptoms and treatment responses to tolterodine in continent relative to incontinent OAB patients.. Data from an open-label, observational study involving 3824 patients with OAB symptoms were analyzed for baseline symptoms and alterations thereof upon a 9 months treatment with 4 mg q.d. tolterodine ER.. Baseline symptoms (number of urgency episodes, total urination frequency, daytime frequency, nocturia, and three scales of OAB severity) were similar in 1147 continent and 2571 incontinent patients, the latter having 4.8+/-3.7 incontinence episodes per 24 h. Tolterodine ER-induced reduction of OAB symptoms was very similar in both groups of patients.. The severity of OAB in continent patients can be similar to that in incontinent ones. Symptom improvement upon treatment with tolterodine ER is very similar in both groups. We propose that continent patients may similarly deserve treatment with a muscarinic receptor antagonist as incontinent ones.

Topics: Aged; Benzhydryl Compounds; Cresols; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Observation; Phenylpropanolamine; Safety; Severity of Illness Index; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urodynamics

This study was undertaken to compare the central nervous system (CNS) tolerability profiles of the extended-release formulations of oxybutynin chloride and tolterodine tartrate in the treatment of women with overactive bladder (OAB), as observed in the OPERA (Overactive bladder: Performance of Extended Release Agents) trial.. The OPERA trial was a randomized, double-blind, active-control comparison of the efficacy and safety of extended-release oxybutynin (10 mg/d) and extended-release tolterodine (4 mg/d) given to 790 women with OAB for 12 weeks. The incidence of reported CNS events was compared between the treatment groups by using the Fisher exact test.. The incidence of CNS adverse events was 9% and 8% for the oxybutynin and tolterodine treatment groups, respectively. The difference between groups was not statistically significant. All reported CNS adverse events were rated as mild or moderate in severity. There were no serious treatment-related adverse events in either group, and discontinuation because of a CNS adverse event was infrequent.. The extended-release formulations of oxybutynin and tolterodine were observed to be associated with a similar low incidence of CNS adverse events, which were mostly mild or moderate in severity.

Topics: Benzhydryl Compounds; Central Nervous System; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Incontinence

The purpose of this study was to examine the responsiveness of the Overactive Bladder questionnaire (OAB-q) during anti-muscarinic treatment.. OAB patients were treated with tolterodine ER 4 mg/day for 12 weeks. The OAB-q and 3-day micturition diaries were collected at baseline, 4, and 12 weeks. The patients' and physicians' perceptions of treatment benefit were assessed at 4 and 12 weeks. Responsiveness of the OAB-q was examined with effect sizes and comparisons to other measures using ANOVAs, t-tests, and correlations.. A total of 865 patients completed the 12-week study (mean age 61 years; 73% female; 89% Caucasian). From baseline to 4 weeks, significant improvements (p < 0.0001) occurred in all OAB-q subscales, which were maintained through week 12. The OAB-q was highly responsive with subscale effect sizes ranging from 0.44 (social interaction) to 1.2 (symptom bother). Significant score changes in all OAB-q subscales (p < 0.05) were associated with reductions of > or = 3 urgency episodes, > or = 3 micturitions, or > or = 1 incontinence episode per day. Improvements in OAB-q scales were associated with changes in patient and physician perceptions of treatment benefit.. The OAB-q was highly responsive and demonstrated responsiveness to reductions in urinary urgency, frequency, and incontinence during antimuscarinic treatment of OAB. The OAB-q appears to be a useful outcome measure for treatments of OAB.

Topics: Benzhydryl Compounds; Cresols; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Sickness Impact Profile; Surveys and Questionnaires; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

The management of chronic conditions, such as overactive bladder (OAB), is often limited by lack of patient adherence to medication. This article compares persistence rates among Medicaid patients who were prescribed 1 of 3 drugs for treatment of OAB: 2 long-acting agents with once-daily dosing, tolterodine tartrate extended-release capsules (tolterodine ER) and oxybutynin chloride extended release (oxybutynin ER), and oxybutynin immediate release (oxybutynin IR), requiring 3 tablets daily.. The study population was comprised of continuously enrolled Medicaid managed care patients filling prescriptions for tolterodine ER, oxybutynin ER, or oxybutynin IR between January 1, 2000, and December 31, 2003. Patients taking any OAB drug in the first 6 months of their observed period of enrollment were excluded to capture new users only. Using survival analyses adjusted for age, sex, and race, the rates of persistence by drug were analyzed. Possession time, the degree to which patients keep medication available even though they may not be taking it daily as prescribed, was also measured.. Of 1637 patients (75% women, 45% African American, 26% younger than 18 years of age), 182 were started on tolterodine ER, 215 on oxybutynin ER, and 1240 on oxybutynin IR. Only 32% of those taking oxybutynin IR and 44% of those taking either long-acting agent remained adherent past 30 days. Of those remaining after 30 days, the risk of nonadherence was higher for oxybutynin ER than for tolterodine ER (hazard ratio = 1.47; 95% confidence interval, 1.01-2.14).. Persistence rates are better for patients taking drugs with once-daily dosing, but there is a need for a better understanding of non-persistent patients.

Topics: Adolescent; Adult; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Medicaid; Middle Aged; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

To compare posttreatment medical costs for patients with overactive bladder (OAB) initiating treatment with oxybutynin chloride immediate release (oxybutynin IR), oxybutynin chloride extended release (oxybutynin ER), or tolterodine extended-release tartrate capsules (tolterodine ER).. Data were drawn from administrative claims of enrollees aged 18 years and older of a large US health plan. OAB patients were identified if at least 1 claim with an International Statistical Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for OAB appeared in medical claims from January 1, 2001, to December 31, 2002. The index prescription was assigned as the first filled prescription of oxybutynin IR (n = 3052), oxybutynin ER (n = 4503), or tolterodine ER (n = 7027) during the subject identification period. Medical costs over the year after initiation were calculated as a function of the health plan and member liability. Independent variables were treatment cohort, sex, age group, geographic region, baseline costs, specific OAB diagnosis codes, and comorbid illnesses. To compare medical costs across treatment cohorts, multivariate regressions correcting for potential selection bias were used.. Multivariate analysis results revealed that costs for patients taking oxybutynin IR were 48% higher than costs for patients taking tolterodine ER (P = .026), and costs for patients taking oxybutynin ER were 191% higher than costs for patients taking tolterodine ER (P <.0001). Adjusted medical costs were dollar 7486 for patients taking oxybutynin IR and dollar 14 766 for patients taking oxybutynin ER compared with dollar 5074 for patients taking tolterodine ER.. Differences in medical costs that remained after adjusting for patient characteristics suggest that treatment with tolterodine ER may be associated with lower medical care utilization after initiation of therapy for OAB.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Female; Health Care Costs; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Retrospective Studies; Selection Bias; Tolterodine Tartrate; United States; Urinary Incontinence

To examine levels of persistence and compliance as well as the economic impact of extended-release tolterodine (tolterodine ER) versus immediate- and extended-release oxybutynin (oxybutynin IR or oxybutynin ER) among commercially-insured patients with overactive bladder (OAB).. Patients with OAB who initiated tolterodine ER, oxybutynin IR, or oxybutynin ER between January 2001 and December 2002 were identified from the PharMetrics Patient-Centric database; the first medication used in this timeframe was used for treatment group assignment (ie, patients were only in 1 group). Exploratory assessment of persistency and compliance was conducted among all treated patients: subjects were matched 1:1 based on the estimated propensity score for tolterodine ER in remaining analyses. Measures included patient characteristics as well as levels of medication, outpatient and inpatient resource utilization, and costs. Primary comparisons were made descriptively; costs were evaluated using generalized linear models with a gamma distribution and log-link function.. Compliance did not differ between tolterodine ER (77.4%) and oxybutynin ER (74.3%), but was lower for oxybutynin IR (60.9%). Mean (+/- standard deviation) duration of therapy was higher for tolterodine ER (139 +/- 132 days) versus oxybutynin ER (115 +/- 122) and oxybutynin IR (60 +/- 85). Totals of 7257 and 5936 matched pairs were available for tolterodine ER versus oxybutynin ER and oxybutynin IR comparisons, respectively. The mean age was 54 years in all groups; the majority was women. Utilization of outpatient and inpatient medical services was consistently lower among tolterodine ER patients in both comparisons. Total costs were slightly lower for tolterodine ER versus oxybutynin ER (dollar 8303 +/- dollar 18 802 vs dollar 8862 +/- dollar 18 684) and oxybutynin IR (dollar 9975 +/- dollar 24860 vs dollar 10521 +/- dollar 22 602); differences were significant after multivariate adjustment.. Use of tolterodine ER results in comparable compliance to oxybutynin ER and longer duration of use relative to either form of oxybutynin. In addition, tolterodine ER may be cost-effective relative to oxybutynin IR or oxybutynin ER among commercially-insured persons with OAB.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Female; Humans; Insurance Coverage; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

The objective of this study was to compare 1-year total healthcare costs for patients with overactive bladder (OAB) initiating treatment with extended-release formulations of tolterodine and oxybutynin: tolterodine tartrate extended-release capsules (tolterodine ER) versus extended-release oxybutynin chloride (oxybutynin ER).. A model was developed from the payer perspective using data from the PharMetrics Patient-Centric database. Monthly discontinuation rates were derived from a cohort of newly treated patients with OAB (tolterodine ER, n = 15 394 or oxybutynin ER, n = 7934). All were assumed to be receiving therapy for at least 1 month. Medical management costs were based on reimbursement for all services for a matched cohort of patients taking tolterodine ER and oxybutynin ER. Medical management costs for those discontinuing therapy were based on patients receiving OAB care without pharmacotherapy (n = 29 992). Drug costs were from AnalySource (December 2004).. After the 11-month follow-up period, 21% of patients taking tolterodine ER and 15% of patients taking oxybutynin ER remained on original therapy. One-year average total costs per patient for those started on tolterodine ER were dollar 8876 and dollar 9080 for oxybutynin ER, a difference of dollar 204 per year. Sensitivity analyses indicated results were robust to changes in drug cost and probability of discontinuation. When discontinuation rates were held equal, cost differences continued to favor tolterodine ER (21%, dollar 272/yr; 15%, dollar 233/yr).. Those taking tolterodine ER had lower monthly drug and medical management costs. This resulted in a total average annual cost savings of dollar 204 per patient for those started on tolterodine ER. At the end of 1 year, patients with OAB were more likely to remain on original drug treatment taking tolterodine ER versus oxybutynin ER.

Topics: Aged; Benzhydryl Compounds; Cohort Studies; Cresols; Delayed-Action Preparations; Health Care Costs; Humans; Mandelic Acids; Models, Theoretical; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; United States; Urinary Incontinence

This article evaluates the safety and tolerability of tolterodine for the treatment of overactive bladder (OAB), which is defined as urinary urgency with or without urgency incontinence, usually with frequency and nocturia, but without infection or pathology. OAB affects tens of millions of people worldwide. Data are summarized from clinical trials and from postmarketing surveillance studies.

Topics: Adult; Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Antimuscarinic agents are the most popular treatment for overactive bladder and their efficacy in man is well documented, producing decreased urinary frequency and an increase in bladder capacity. During cystometry in rats, however, the main effect reported after acute treatment with antimuscarinics is a decrease in peak micturition pressure together with little or no effect on bladder capacity. In the present experiments we studied the effects, in rats, of the two most widely used antimuscarinic drugs, namely oxybutynin and tolterodine, utilising several different cystometrographic conditions. The aim was to determine the experimental conditions required to reproduce the clinical pharmacological effects of antimuscarinic agents, as seen in humans, in particular their ability to increase bladder capacity.. Intravenous or oral administration of tolterodine or oxybutynin in conscious rats utilized 1 day after catheter implantation and with saline infusion at constant rate of 0.1 ml/min, gave a dose-dependent decrease of micturition pressure (MP) with no significant change in bladder volume capacity (BVC). When the saline infusion rate into the bladder was decreased to 0.025 ml/min, the effect of oral oxybutynin was similar to that obtained with the higher infusion rate. Also, experiments were performed in rats in which bladders were infused with suramin (3 and 10 microM) in order to block the non-adrenergic, non-cholinergic component of bladder contraction. Under these conditions, oral administration of oxybutynin significantly reduced MP (as observed previously), but again BVC was not significantly changed. In conscious rats with bladders infused with diluted acetic acid, both tolterodine and oxybutynin administered at the same doses as in animals infused with saline, reduced MP, although the reduction appeared less marked, with no effect on BVC. In conscious rats utilized 5 days after catheter implantation, a situation where inflammation due to surgery is reduced, the effect of tolterodine (i.v.) and oxybutynin (p.o.) on MP was smaller and similar, respectively, to that observed in rats utilized 1 day after catheter implantation, but the increase of BVC was not statistically significant. In anesthetized rats, i.v. administration of oxybutynin again induced a significant decrease in MP, although it was of questionable relevance. Both BVC and threshold pressure were not significantly reduced. The number and amplitude of high frequency oscillations in MP were unmodified by treatment. Finally, in conscious obstructed rats, intravenous oxybutynin did not modify frequency and amplitude of non-voiding contractions or bladder capacity and micturition volume.. Despite the different experimental conditions used, the only effect on cystometrographic parameters of oxybutynin and tolterodine in anesthetized and conscious rats was a decrease in MP, whereas BVC was hardly and non-significantly affected. Therefore, it is difficult to reproduce in rats the cystometrographic increase in BVC as observed in humans after chronic administration of antimuscarinic agents, whereas the acute effects seem more similar.

Topics: Animals; Benzhydryl Compounds; Cresols; Male; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Tolterodine Tartrate; Urinary Bladder; Urinary Catheterization; Urinary Incontinence; Urination

We determined whether the effects of antimuscarinics depend on the suppression of C-fiber bladder afferent nerves. We administered tolterodine intravenously or intravesically.. To induce C-fiber bladder afferent nerve desensitization resiniferatoxin (RTX) (0.3 mg/kg) was injected subcutaneously in female Sprague-Dawley rats 2 days prior to left middle cerebral artery occlusion (MCAO). As controls, we used rats treated with ethanol and saline vehicle (VEH). Insertion of a polyethylene catheter through the bladder dome and MCAO were performed using halothane anesthesia. The effects of intravenous (0.2 to 2000 nM/kg) or intravesical (0.2 or 2 nM) tolterodine, an antimuscarinic agent, on cystometrography were investigated in conscious rats with a cerebral infarct (CI). Tolterodine was instilled intravesically for 30 minutes and cystometry was repeated.. Bladder capacity (BC) was markedly decreased after MCAO in RTX treated (RTX-CI) and VEH treated (VEH-CI) rats. Low tolterodine doses (0.2 or 2 nM/kg) significantly increased BC in VEH-CI rats without increasing residual volume but it had no effects on BC in RTX-CI rats. At the highest dose (2,000 nM/kg) the drug significantly decreased bladder contraction pressure and increased residual volume in RTX-CI and VEH-CI rats. Intravesical administration of tolterodine (0.2 or 2 nM) significantly increased BC in VEH-CI rats. However, tolterodine had no effect on BC in RTX-CI rats.. These results suggest that at low doses tolterodine exerts an inhibitory effect on C-fiber bladder afferent nerves, thereby, improving BC during the storage phase.

Topics: Administration, Intravesical; Afferent Pathways; Analysis of Variance; Animals; Benzhydryl Compounds; Cresols; Disease Models, Animal; Female; Infusions, Intravenous; Muscarinic Antagonists; Nerve Fibers, Unmyelinated; Phenylpropanolamine; Probability; Rats; Rats, Sprague-Dawley; Reference Values; Statistics, Nonparametric; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Incontinence

To assess the reliability of symptom reports in 3-day vs 7-day bladder diaries used in clinical trials of patients with overactive bladder (OAB) and to compare those results and related issues with previous reports.. We analysed two large-scale, randomized, phase 3 clinical trials of the use of transdermal oxybutynin for treating patients with OAB. The first trial (Trial A, 520 patients) compared three doses of transdermal oxybutynin (1.3, 2.6 and 3.9 mg/day) with placebo. Patients documented their OAB symptoms in a 7-day diary. The second clinical study (Trial B, 361 patients) compared the efficacy of 3.9 mg/day transdermal oxybutynin with 4 mg/day extended-release tolterodine and with placebo; this trial required symptom recording for only 3 days. The internal consistency of the data from the 7-day trial was determined and then compared with the 3-day trial results.. Patients on transdermal oxybutynin or long-acting tolterodine for their OAB symptoms showed a clinically and statistically significant improvement, results that were documented in both 3-day and 7-day bladder diaries. However, compared with 7-day symptom records, 3-day diaries were associated with significantly better compliance with record-keeping (P < 0.001).. Seven-day diaries used in clinical trials supply accurate and reproducible data on clinical manifestations of OAB, but 3-day diaries are equally effective and have the potential for better accuracy through increased patient convenience. Three-day diaries may also reduce the tendency for patients to complete gaps in record-keeping from memory.

Topics: Benzhydryl Compounds; Chi-Square Distribution; Cresols; Humans; Mandelic Acids; Medical Records; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Time; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Double-Blind Method; Humans; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence

Topics: Accommodation, Ocular; Benzhydryl Compounds; Cresols; Eye Diseases; Humans; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Exercise; Female; Humans; Life Style; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Sex Factors; Tolterodine Tartrate; United States; Urinary Incontinence

To study the urinary symptoms and quality of life changes in Thai women with overactive bladder (OAB) after tolterodine treatment.. Thirty women (aged 30-77 years) diagnosed as having OAB at the Gynecology Clinic, King Chulalongkorn Memorial Hospital from January to April 2004 were included in the present study. Tolterodine 2 mg, twice daily was given. After 8 weeks treatment, changes in micturition diary variables and tolerability were determined. Short form 36 (SF36) questionaires (Thai version) were given before and after 8 weeks of treatment.. At 8 weeks, all micturition per day decreased from 16. 7 +/- 5. 3 to 6. 7 +/- 2.4 times per day. The number of nocturia episodes decreased from 5.4 +/- 4.2 to 1.1 +/- 1.0 times per night. The most common side effect was dry month in 5 cases (16.7%) with 2 cases reporting a moderate degree and 1 case with severe degree. Only one case (3.3%) withdrew from the present study due to a severe dry mouth. The SF-36 scores changed significantly in the domains of physical functioning, role function emotional, social function and mental heath.. Tolterodine was well tolerated and its effects improved the quality of life in Thai women with OAB.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Female; Humans; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Prospective Studies; Quality of Life; Surveys and Questionnaires; Thailand; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Topics: Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Drug Evaluation; Government Regulation; Humans; Muscarinic Antagonists; New Zealand; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Topics: Activities of Daily Living; Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Germany; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Muscle Hypertonia; Patient Satisfaction; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence; Urodynamics

Clinicians often encounter patients with dementia and urge incontinence who might benefit from both an anticholinergic medication and a cholinesterase inhibitor. At first glance, this combination would seem to violate basic principles of geriatric pharmacology, as the drugs appear to be working at cross-purposes and anticholinergic medications are notorious for worsening cognitive function in susceptible patients. A case is presented and discussed in which this combination was clinically effective and pharmacologically sound.

Topics: Aged; Benzhydryl Compounds; Cholinesterase Inhibitors; Cresols; Dementia; Donepezil; Drug Interactions; Drug Therapy, Combination; Female; Humans; Indans; Muscarinic Antagonists; Phenylpropanolamine; Piperidines; Tolterodine Tartrate; Urinary Incontinence

To develop a short version of the King's Health Questionnaire (KHQ), as there is a practical need to have a shorter version to summarize the eight domain scores into fewer domains.. Data from 293 patients were obtained from a randomized, double-blind, placebo-controlled clinical trial in Japan of oxybutynin and tolterodine in patients with symptoms of an overactive bladder. The KHQ has two single-item and six multiple-item domains. To construct the short form of the KHQ one item was selected from the each of multiple-item domains, based on standardized structural coefficients estimated by confirmatory factor analysis (CFA) in a previous study. These six items include the domains: 'daily activities from role limitation', 'travel from physical limitation', 'social life from social limitation', 'family life from personal relationship', 'depressed from emotion' and 'tired from sleep and energy'. Based on the six selected items a series of psychometric analyses were conducted.. Exploratory factor analysis (EFA) with promax rotation identified two factors 'limitation of daily life' (LDL) and mental health. LDL consisted of 'daily activities', 'travel' and 'social life', and mental health included 'family life', 'depressed' and 'tired'. Based on the results from the EFA, the second-order factor structure was tested by CFA. The model fitted the data well for both the male and female model. The KHQ short form showed excellent reliability with Cronbach's alpha coefficients for LDL and mental health for both genders. The domains in the short form were responsive to clinical efficacy variables, and had statistically significant sensitivity to change in the patients' perception of bladder condition in all domains.. These analyses confirm the psychometric properties and clinical validity of the short-form KHQ, which appears to offer a practical, valid and reliable health-related quality-of-life instrument.

Topics: Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Reproducibility of Results; Surveys and Questionnaires; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

To assess the efficacy of combined treatment with doxazosin and tolterodine, as although alpha-blockers are commonly used and generally effective in men with symptomatic bladder outlet obstruction (BOO), a subset of men with BOO and overactive bladder (OAB) symptoms often complain of persistent symptoms.. In a prospective study of 144 consecutive men with BOO at one tertiary urology centre, all had a baseline pressure-flow urodynamic study and were then subdivided into those with BOO or BOO + OAB, based on absence or presence of involuntary detrusor contractions. The Abrams-Griffiths nomogram was used to determine obstructive BOO. After the initial evaluation, all patients were treated with doxazosin 4 mg/day for 3 months. In patients with no symptomatic improvement, tolterodine 2 mg twice daily was added for an additional 3 months.. Of the 144 patients, 76 (53%) were diagnosed as having BOO and 68 (47%) BOO + OAB. The patients with BOO + OAB were older (P < 0.05) and had a higher International Prostate Symptom Score. After 3 months of treatment with doxazosin, 60 (79%) with BOO and 24 (35%) BOO + OAB reported a symptomatic improvement. In those patients with no improvement, six of 16 with BOO and 32 of 44 (73%) with BOO + OAB improved after adding tolterodine. Acute urinary retention developed in only two of 60 men (3.3%) treated with the combined therapy.. About half of men with symptomatic BOO had an OAB; while about three-quarters of men with symptomatic BOO and no OAB improved with doxazosin, only a third with BOO + OAB were helped with doxazosin alone. Combining tolterodine with doxazosin was effective in three-quarters of men with BOO + OAB. Overall, most men with BOO with or with no OAB were helped with doxazosin alone or with the addition of tolterodine.

Topics: Adrenergic alpha-Antagonists; Benzhydryl Compounds; Cresols; Doxazosin; Humans; Male; Middle Aged; Phenylpropanolamine; Prospective Studies; Prostatic Hyperplasia; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder Neck Obstruction; Urinary Incontinence; Urodynamics

Oxybutynin and tolterodine are two drugs widely used for the management of overactive bladder and urge urinary incontinence. The once-daily, extended-release formulations benefit from being well tolerated and efficacious. However, their costs, compared with generic immediate-release (IR) oxybutynin, are significantly greater. This study compared the cost effectiveness of oxybutynin extended-release (Oxy-XL), tolterodine extended-release (Tol-ER), tolterodine immediate-release (Tol-IR) and oxybutynin immediate-release (Oxy-IR).. A cost-effectiveness model.. A systematic review that identified appropriate randomised clinical trials provided evidence on efficacy. Empirical models of drug effects (number of incontinent-free weeks) and persistence (proportion of patients still on therapy) were constructed in order to determine clinical effectiveness which was combined with cost data (direct medical costs to the UK NHS, year 2001 values) to calculate the drugs' cost-effectiveness from the perspective of the NHS. Univariate sensitivity analyses were conducted to test the robustness of the results.. Hypothetical cohort of patients with urge incontinence associated with overactive bladder.. The incremental cost per incontinent-free week for Oxy-IR (versus no treatment) ranged from pound sterling 2.58 to pound sterling 16.59. Oxy-XL and Tol-ER were more effective than Oxy-IR but at additional costs per incontinent-free week. Tol-IR did not appear to be a cost-effective option as it was less effective and more costly than the extended-release formulations. Uncertainty surrounding the health and cost consequences of early discontinuation affected these results, although the model results were robust to parameter uncertainty.. Oxy-IR, Oxy-XL and Tol-ER appear to be cost-effective options for the management of urge incontinence from the NHS perspective. A decision among the treatments depends on the acceptable cost per additional incontinent-free week.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Delayed-Action Preparations; Drug Costs; Female; Humans; Male; Mandelic Acids; Middle Aged; Models, Economic; Muscarinic Antagonists; Phenylpropanolamine; Randomized Controlled Trials as Topic; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Quinuclidines; Randomized Controlled Trials as Topic; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Incontinence; Urodynamics

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Diagnosis, Differential; Female; Hallucinations; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

To assess the safety and efficacy of tolterodine tartrate prescribed to children who previously failed to tolerate oxybutynin chloride.. We reviewed 34 children, followed for>1 year, who were prospectively crossed-over from oxybutynin to tolterodine because of side-effects. The initial diagnosis was dysfunctional voiding in 31 patients. All patients were placed on a behavioural modification protocol. When their symptoms did not improve after 6 months, treatment with an anticholinergic agent was considered. Urodynamic studies were conducted in 20 patients, confirming uninhibited contractions in 19. The remaining 14 patients were empirically started on antimuscarinic or anticholinergic agents. The 34 patients were treated with oxybutynin for a median (range) of 6 (2-84) months. When significant side-effects were reported, they were crossed over to tolterodine. The efficacy of tolterodine was assessed as defined by the International Children's Continence Society, with tolerability assessed and side-effects documented using a questionnaire.. The mean age at the first dose of tolterodine was 8.9 years; the dose was 1 mg twice daily for 12 patients and 2 mg twice daily for 22. The median treatment with tolterodine was 11.5 months, with 20 (59%) patients reporting no side-effects; six described the same but tolerable side-effects as with oxybutynin. Eight patients discontinued tolterodine because of side-effects after a median (range) of 5 (1-11) months. The efficacy of tolterodine was comparable with that of oxybutynin, as reported by the questionnaire and voiding diaries. The reduction in wetting episodes at 1 year was> 90% in 23 (68%), more than half in five and less than half (or failure) in six patients.. Tolterodine is tolerated well in children. In this subgroup of patients who could not tolerate oxybutynin, 77% were able to continue tolterodine treatment with no significant side-effects.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Cross-Over Studies; Enuresis; Female; Humans; Infant; Male; Mandelic Acids; Phenylpropanolamine; Prospective Studies; Tartrates; Tolterodine Tartrate; Treatment Failure; Urinary Incontinence

Topics: Adrenergic Uptake Inhibitors; Behavior Therapy; Benzhydryl Compounds; Benzilates; Biofeedback, Psychology; Cholinergic Antagonists; Contraindications; Cresols; Deamino Arginine Vasopressin; Electric Stimulation Therapy; Female; Humans; Imipramine; Male; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Physical Therapy Modalities; Renal Agents; Tolterodine Tartrate; Urinary Incontinence; Urinary Incontinence, Stress

Topics: Benzhydryl Compounds; Child; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Dosage Forms; Humans; Mandelic Acids; Phenylpropanolamine; Research Design; Retrospective Studies; Tartrates; Tolterodine Tartrate; Urinary Incontinence

Topics: Administration, Cutaneous; Administration, Oral; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Randomized Controlled Trials as Topic; Salivation; Tolterodine Tartrate; Treatment Outcome; United States; Urinary Incontinence; Urination

Topics: Aged; Benzhydryl Compounds; Cresols; Female; Hallucinations; Humans; Memory Disorders; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence

Topics: Aged; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Geriatric Assessment; Geriatric Nursing; Humans; Mandelic Acids; Muscarinic Antagonists; Nurse's Role; Nursing Assessment; Nursing Homes; Phenylpropanolamine; Prevalence; Toilet Training; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

We compared the importance of patient age and gender relative to the intensity of baseline symptoms of overactive bladder in the therapeutic response to the muscarinic receptor antagonist tolterodine.. Data from an open label, observational study of 2,250 patients with overactive bladder treated for 12 weeks with tolterodine were analyzed for alterations in frequency, urgency and urge incontinence, and for global efficacy and tolerability using logistic regression analysis, stratifying for gender, age, baseline symptom intensity and tolterodine dose.. Gender or tolterodine dose were not consistently associated with altered treatment efficacy. Greater age was associated with a slight but statistically significant decrease in treatment efficacy. Patients with great baseline symptom intensity had greater treatment associated improvement but a lesser chance to become symptom-free. Even with a large number of patients no statistically significant gender or age associated alterations in the tolerability of tolterodine treatment were detected.. The extent of the therapeutic response to tolterodine is largely determined by the extent of baseline symptoms. While gender does not affect the efficacy or tolerability of tolterodine in a clinically relevant manner, advanced age is associated with a slight decrease in efficacy but not in tolerability.

Topics: Age Factors; Aged; Benzhydryl Compounds; Cresols; Female; Humans; Logistic Models; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Sex Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Incontinence; Urination Disorders

Topics: Adrenergic alpha-Antagonists; Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Deamino Arginine Vasopressin; Humans; Imipramine; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Renal Agents; Tolterodine Tartrate; Urinary Incontinence

Topics: Behavior Therapy; Benzhydryl Compounds; Cresols; Female; Humans; Male; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Physical Therapy Modalities; Tolterodine Tartrate; United States; Urinary Incontinence

To report a patient with an acute mixed liver injury associated with tolterodine therapy.. An 81-year-old white woman with urge incontinence experienced malaise, fever, and gastrointestinal disturbances 18 days after starting tolterodine 2 mg twice daily. The patient's concurrent medications included flunitrazepam, diclofenac, and dorzolamide/timolol eye drops. Laboratory examination was consistent with the presentation of an acute mixed liver injury with increased transaminase enzymes, alkaline phosphatase, gamma-glutamyltransferase, and bilirubin. Additionally, she had mild leukocytosis with eosinophilia. After tolterodine was discontinued, the abnormal liver and hematologic parameters returned to normal within 4 weeks.. Tolterodine, a muscarinic receptor antagonist, has predominantly anticholinergic effects. To our knowledge, this is the first case published describing tolterodine-associated acute mixed liver injury. However, some of the patient's additional symptoms can also be considered part of a drug-induced hypersensitivity syndrome. This is usually defined by the triad of fever, cutaneous reaction, and involvement of internal organs, mainly affecting the liver. The close temporal relationship between the start of tolterodine therapy and the first symptoms and the reversibility after dechallenge led us to conclude that the adverse reaction was possibly related to tolterodine exposure.. Our case illustrates that tolterodine may rarely be associated with liver injury. This may have been an organ manifestation of tolterodine-induced hypersensitivity syndrome.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Benzhydryl Compounds; Bilirubin; Cresols; Female; Fever; gamma-Glutamyltransferase; Humans; Liver Failure, Acute; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Transaminases; Urinary Incontinence

Tolterodine was recently approved for the treatment of incontinence and overactive bladder in adults, and has fewer side effects than oxybutynin. We evaluated the safety and efficacy of tolterodine in children with dysfunctional voiding.. We retrospectively reviewed our experience with 30 pediatric patients treated with tolterodine for a primary diagnosis of dysfunctional voiding. Patients were treated with adult doses of tolterodine and behavioral modifications. Standard definitions determined by the International Children's Continence Society were adapted to designate final treatment outcomes on medication as cured-greater than 90% reduction in wetting episodes, improved-greater than 50% reduction or failed-less than 50% reduction.. The children were 4 to 17 years old (mean age 8.7) and were treated with tolterodine for an average of 5.2 months. The final dose was 1 mg. twice daily in 1, 2 mg. twice daily in 27 and 4 mg. twice daily in 2 patients. Wetting episodes were cured in 10 (33%), improved in 12 (40%), and failed to show improvement in 8 (27%) cases. Four patients (13.3%) reported side effects and only 1 discontinued the medication due to diarrhea. There were no reports of hyperpyrexia, flushing or intolerance to sunshine and outdoor temperature.. Our results demonstrate that tolterodine at adult doses without titration can be used safely to decrease wetting episodes in children with dysfunctional voiding. Controlled clinical trials should be completed to evaluate further efficacy and safety in children.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Retrospective Studies; Tolterodine Tartrate; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Mandelic Acids; Middle Aged; Phenylpropanolamine; Prospective Studies; Randomized Controlled Trials as Topic; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

The objectives of this study were to determine age- and gender-specific drug treatment prevalence rates for overactive bladder (OAB), and to compare resource use and costs among MCO members receiving drug treatment for OAB. Administrative claims data from seven affiliated health plans were analyzed for 8,661 members with a diagnosis or treatment indicative of OAB during 1998. Resource use and associated costs were analyzed over a four-month follow-up. In 1998, the prevalence of OAB among plan members was 1.1%. Of the patients with OAB, 71% did not receive pharmacotherapy. After multivariate analysis, treatment with tolterodine, oxybutynin, or other OAB treatment did not significantly affect the percent change in total per patient per month (PPPM) costs compared with the group not receiving a pharmacologic agent. Although the adjusted percent change in PPPM pharmacy costs was significantly higher within the tolterodine group, medical and total PPPM costs were not.

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Comorbidity; Cost of Illness; Cresols; Female; Health Care Costs; Humans; Insurance Claim Reporting; Longitudinal Studies; Male; Managed Care Programs; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Prevalence; Retrospective Studies; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Evidence-Based Medicine; Humans; Mandelic Acids; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Delayed-Action Preparations; Humans; Mandelic Acids; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Statistics as Topic; Tolterodine Tartrate; Urinary Incontinence

Tolterodine is a novel muscarinic receptor antagonist for the treatment of overactive bladder.. The purpose of this study was to examine the cost-effectiveness of tolterodine for patients with urge incontinence (UI) who discontinue initial therapy with oxybutynin in a Canadian setting.. We compared 2 treatment strategies for the management of adult patients with UI: (1) generic oxybutynin with no further treatment for patients who discontinue and (2) generic oxybutynin with switch to tolterodine (2 mg BID) for patients who discontinue. We developed a 1-year Markov model (4-week cycle length) with transitions between disease states of normal, mild, moderate, and severe. Transition probabilities over 12 weeks were obtained from randomized trial data, and drug discontinuation rates were obtained from Quebec prescription claims data. Outcome measures were time in "normal" health state and quality-adjusted life-years (QALYs) using EuroQol-5D utility scores from a survey of Swedish patients with overactive bladder. Costs to the health care payer and patient out-of-pocket costs (in Canadian dollars) were included.. For patients who discontinue oxybutynin, the use of tolterodine is associated with approximately 6 months per year in a normal health or mild disease state, compared with approximately 3 months for those who do not receive further drug therapy after discontinuation. Tolterodine use resulted in an annual additional cost per patient of Can $163. The incremental cost per QALY was Can $9,982 and appeared to be robust to alternative model parameter assumptions.. Use of tolterodine in patients with UI who discontinue initial therapy with generic oxybutynin lies within currently accepted benchmarks for cost-effectiveness.

Topics: Benzhydryl Compounds; Canada; Cost-Benefit Analysis; Cresols; Economics, Pharmaceutical; Humans; Mandelic Acids; Markov Chains; Muscarinic Antagonists; Parasympatholytics; Phenylpropanolamine; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Severity of Illness Index; Tolterodine Tartrate; Urinary Incontinence

We evaluated adherence to treatment with immediate-release (IR) oxybutynin (515 patients) and tolterodine (505 patients) for detrusor overactivity through retrospective analysis of a pharmacy claims database. Outcomes included percentage of patients continuing therapy for 6 months, medication possession ratios, and time to discontinuation of therapy. The proportion of patients continuing therapy for 6 months was statistically superior for tolterodine (32%) compared with IR oxybutynin (22%, p<0.001). Medication possession ratios were also superior for patients in the tolterodine group (medians 0.83 and 0.64, ranges 0.11-1.15 and 0.07-1.13, respectively, p<0.001). Oxybutynin was discontinued significantly earlier (mean 45 days) than tolterodine (mean 59 days, p<0.001) and was switched to another therapy more commonly than tolterodine (19% and 14%, respectively). Tolterodine was favored over oxybutynin for several measurements of patient adherence. However, less than one-third of patients continued therapy with either agent for 6 months. The clinical relevance of these differences is unknown.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cohort Studies; Cresols; Drug Prescriptions; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Parasympatholytics; Pharmaceutical Services; Phenylpropanolamine; Retrospective Studies; Time Factors; Tolterodine Tartrate; Urinary Incontinence

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder Diseases; Urinary Incontinence; Xerostomia

Topics: Aged; Behavior Therapy; Benzhydryl Compounds; Combined Modality Therapy; Cresols; Female; Humans; Male; Mandelic Acids; Multicenter Studies as Topic; Muscarinic Antagonists; Muscle Contraction; Parasympatholytics; Phenylpropanolamine; Randomized Controlled Trials as Topic; Tolterodine Tartrate; United States; Urinary Incontinence

Topics: Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Female; Humans; Male; Mandelic Acids; Phenylpropanolamine; Tartrates; Tolterodine Tartrate; Urinary Incontinence

Topics: Benzhydryl Compounds; Cresols; Humans; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Incontinence