tolterodine-tartrate and Urinary-Bladder--Neurogenic

To summarize the differences in urodynamic outcomes between oral antimuscarinic drugs and OnabotulinumtoxinA, and finding a therapy that maintains good urodynamics in neurogenic detrusor overactivity (NDO). We conducted a literature search of EMBASE and PubMed, with the language limited to English. In the analysis, all of the published randomized trials of OnabotulinumtoxinA or antimuscarinic drugs used to treat NDO were found and the results were finally obtained through Bayesian model analysis. A total of 12 RCTs and 2208 patients were included. OnabotulinumtoxinA 300U was superior to other drugs in terms of MCC, volume at IDC, and Pdet

Topics: Bayes Theorem; Botulinum Toxins, Type A; Humans; Muscarinic Antagonists; Network Meta-Analysis; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

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

Overactive bladder (OAB) is a condition defined by its symptoms--urinary urgency with or without urgency urinary incontinence and often with frequency and nocturia. As such, determining the efficacy of OAB treatments using objective measures, such as urodynamic testing, can be difficult. A better means of gauging treatment efficacy for symptom-based conditions is through the use of patient-reported outcomes (PROs). With PROs, clinicians can gain insight into how a treatment affects a patient's symptoms and whether improvement in symptoms has a positive effect from the patient's perspective. PROs are increasingly being included as end points in clinical trials, including those of antimuscarinic drugs for OAB. Consequently, clinicians should become familiar with the most commonly used instruments. We provide an overview of instruments used to assess symptoms, health-related quality of life, and treatment satisfaction in patients with OAB and discuss how PROs can be incorporated into clinical trial protocols.

Topics: Benzhydryl Compounds; Clinical Trials as Topic; Cresols; Health Status; Humans; Mandelic Acids; Muscarinic Antagonists; Patient Compliance; Patient Satisfaction; Phenylpropanolamine; Quality of Life; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence, Stress

Daytime wetting is a common problem with various causes that can usually be identified through a careful history, thorough physical examination, and urinalysis. Conservative approaches to therapy have a successful outcome in most children. Invasive diagnostic imaging studies and pharmacologic or surgical intervention are necessary only for carefully selected children.

Topics: Arousal; Benzhydryl Compounds; Child; Child, Preschool; Constipation; Cresols; Diurnal Enuresis; Humans; Laughter; Mandelic Acids; Muscarinic Antagonists; Pelvic Floor; Phenylpropanolamine; Toilet Training; Tolterodine Tartrate; Ultrasonography; Urinary Bladder; Urinary Bladder, Neurogenic; Urinary Incontinence, Urge; Urodynamics; Vesico-Ureteral Reflux

It is estimated that almost 70% of patients affected by multiple sclerosis (MS) suffer from urinary symptoms, with devastant impact on Quality of Life (QoL). The major aims of management should be to ameliorate the patients quality of life and to prevent the frequent complications of bladder dysfunction such as infention and renal damage. Therapy can usually eliminate or reduce the symptoms of neuropathic bladder. In the following pages is discussed the complex management of urinary symptoms in MS patients.

Topics: Antidepressive Agents, Tricyclic; Benzhydryl Compounds; Botulinum Toxins; Capsaicin; Cresols; Diterpenes; Electric Stimulation Therapy; Humans; Multiple Sclerosis; Muscarinic Antagonists; Phenylpropanolamine; Prognosis; Quality of Life; Time Factors; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urodynamics

A few decades ago, urinary diversion, usually with an ileal conduit, was the ultimate outcome for most children with spina bifida. The revolutionary institution of clean intermittent catheterization has changed the algorithm totally. Furthermore many new drugs have been developed during the past decade and have decreased the need for surgery dramatically. In this article, we will focus on the most recent data on new modalities of therapy to help avoid urinary diversion or bladder augmentation.. In addition to clean intermittent catheterization and oxybutynin treatment, a new generation of anticholinergic medications, such as tolterodine, has been developed. For patients who drop out because of the side-effects of oral administration, new methods of administration are now available, including extended release and intravesical instillation. For those unresponsive, botulinum-A toxin and resiniferatoxin are two relatively new drugs in the field, administered as intravesical injection and instillation, respectively. Intravesical or transdermal electrical stimulation, sacral nerve stimulation and biofeedback therapy are under development, but as currently administered, are not yet completely successful.. Although life-saving in many respects, bladder augmentation introduces life-long risks of its own. Our goal in describing 'conservative' management is to prevent this step. Many alternatives to surgery are available now and more effective strategies are under development.

Topics: Anti-Dyskinesia Agents; Benzhydryl Compounds; Biofeedback, Psychology; Botulinum Toxins; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Diterpenes; Electric Stimulation Therapy; Humans; Infant; Infant, Newborn; Mandelic Acids; Meningomyelocele; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Catheterization

Overactive bladder (OAB) is a disabling disorder. Treatment of cases with OAB includes behavioral, pharmacological, surgical interventions and peripheral electrical stimulation. The goal of this study was to determine effects of posterior tibial nerve stimulation on sexual function and pelvic disorders in women with Overactive bladder (OAB). Fifty women were randomly assigned to PTNS (posterior tibial nerve stimulation) plus tolterodine or tolterodine alone treatment. Tolterodine group received 4 mg tolterodine daily for three months while the other group received this treatment plus percutaneous tibial nerve stimulation for 12 consequence weeks. Two in PTNS group and 8 in the control group withdrew from the study. Age, education level, and occupation status were not significantly different between two groups. Mean total FSFI and its subscales were not significantly different before and after treatment between two groups. Urine leakage associated with a feeling of urgency and loss of stool or gas from the rectum beyond patient's control became significantly different after treatment between two groups. Posterior tibial nerve stimulation could help urinary problems in women with a neurologic bladder.

Topics: Adult; Benzhydryl Compounds; Cresols; Electric Stimulation Therapy; Female; Humans; Middle Aged; Phenylpropanolamine; Rectum; Tibial Nerve; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

To evaluate the comparative efficacy and safety of extended-release (ER) and instant-release (IR) tolterodine preparations in a pediatric population with neural tube defects having cystometric abnormalities.. Twenty-five patients with neural tube defects and a similar demographic profile underwent a routine hemogram, liver function tests, renal function tests, urine culture, X-ray lumbo-sacral spine, and renal and bladder ultrasound. Vesicoureteric reflux was diagnosed by micturating cystourethrogram under fluoroscopy. Dimercaptosuccinic acid renal scintigraphy was performed to study the presence or absence of renal scars. Patients were treated with tolterodine ER (Group I: 2mg once daily for 21 days) and tolterodine IR (Group II: 2mg twice daily for 21 day) in a cross-over study with a 10-day washout period between administrations. Evaluation was by subjective assessment, visual analog scale, urodynamic assessment and adverse drug reaction monitoring.. There was ultrasound evidence of hydroureteronephrosis in 20% of the patients. One patient out of 25 had impaired renal function and eight patients had renal scarring on dimercaptosuccinic acid scans. Both forms of the drug increased the maximum cystometric bladder capacity, decreased detrusor leak pressures and increased compliance compared to pre-therapy levels (P=0.0001). Visual analog scale showed a significant clinical improvement with both ER and IR tolterodine. A significant increase in maximum bladder capacity in the group receiving IR tolterodine as compared to the ER preparation was noted (P=0.0001). The decrease in detrusor leak pressures and improvement in compliance were not significantly different between the groups. No adverse effects of hyperpyrexia, flushing or intolerance to outdoor temperatures, or dryness of mouth were observed in either group. No patient suffered from constipation.. ER tolterodine 2mg once daily is as effective and well tolerated in children with neurogenic bladder as IR tolterodine 2mg twice a day. The latter was found to be more effective in terms of urodynamic parameters. ER formulation of tolterodine is less expensive and has the advantage of single dosage.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Delayed-Action Preparations; Humans; Muscarinic Antagonists; Neural Tube Defects; Phenylpropanolamine; Pressure; Tolterodine Tartrate; Treatment Outcome; Ultrasonography; Urinary Bladder; Urinary Bladder, Neurogenic

Patients with neurogenic bladder dysfunction demonstrate an insufficient treatment outcome under dosage-escalated monotherapy. With the objectives of continence and normalised bladder pressure, safe and tolerable non-invasive treatment alternatives were evaluated by using combined antimuscarinics.. Twenty-seven patients who were previously registered in a doubled antimuscarinics study were enrolled in this study. The patients demonstrated urodynamic-proven neurogenic bladder dysfunction with incontinence, reduced bladder capacity, and increased intravesical pressure, resulting from spinal cord injury (n=21); spinal cord dysplasia (myelomeningocele; n=3); multiple sclerosis (n=2), and viral encephalomyelitis (n=1). On the basis of the initial study treatment, they were allocated into three groups and treated with two antimuscarinics. Before enrollment, at 4 wk, and at 6 mo, patients underwent urodynamics and recorded bladder diaries, including side-effects.. In all three groups, significant changes were noted at the 4-wk follow-up. Incontinence events decreased from an average of 7 to 1 event per day. The average median bladder capacity (180-393 ml) and reflex volume (125-335 ml) increased; detrusor compliance also improved (average, 15-33 ml/cm H2O). Seven patients reported side-effects; two discontinued the successful treatment. Two other patients did not reach satisfactory amelioration of the detrusor dysfunction.. With combined high-dosage antimuscarinic medications, 85% of the patients who previously demonstrated unsatisfactory outcome with dosage-escalated monotherapy were treated successfully. The appearance of side-effects was comparable to that of normal-dosed antimuscarinics. Further studies are required to investigate the long-term pharmacological and physiological background of our findings.

Topics: Adolescent; Adult; Benzhydryl Compounds; Benzilates; Cresols; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nortropanes; Parasympatholytics; Phenylpropanolamine; Spinal Cord Diseases; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urodynamics

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

Three exploratory studies were conducted to investigate the pharmacokinetics (PK) and safety of tolterodine in children 1 month to 15 years old with neurogenic detrusor overactivity. We urodynamically evaluated the dose and concentration effects of tolterodine to establish safe and effective dosing regimens.. Three open-label, dose escalating studies were conducted in children with stable neurological disease and detrusor overactivity. In studies 1 (patient aged 1 month to 4 years) and 2 (5 to 10 years) patients received 0.03, 0.06 and 0.12 mg/kg tolterodine solution day twice daily for 4 weeks each. In study 3 (patient age 11 to 15 years) patients received 2, 4 and 6 mg tolterodine extended-release capsules once daily for 4 weeks each. PK was assessed after 8 weeks, urodynamic assessments were conducted after each 4-week dosing period and 3-day micturition diaries were completed.. Patients in studies 1 (19) and 2 (15) showed some dose related increases in volume to first detrusor contraction and cystometric bladder capacity. In study 3 (11 patients) there were no obvious dose-response relationships. PK results from studies 1 and 2 suggest that there was no apparent effect of age (< or =10 y) on these parameters. In study 3 time of maximum observed serum concentration and apparent terminal half-life were delayed, which is consistent with the extended-release formulation. Tolterodine was well tolerated, and there was no apparent relationship between tolterodine dose and adverse events in any study.. These results support the safety of age and body weight adjusted dosing regimens for further clinical evaluation of tolterodine in children with neurogenic detrusor overactivity.

Topics: Adolescent; Area Under Curve; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Female; Humans; Infant; Male; Muscarinic Antagonists; Phenylpropanolamine; Safety; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Bladder, Neurogenic; Urodynamics

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

Treatment with the antimuscarinic agents tolterodine and oxybutynin is the mainstay of therapy for overactive bladder, a chronic and debilitating condition characterized by urinary urgency with or without urge incontinence, usually in combination with urinary frequency and nocturia. This study consisted of two trials; in one, patients with overactive bladder were randomized to 8 weeks of open-label treatment with either 2 mg or 4 mg of once-daily extended-release tolterodine (TER), and in the other to 5 mg or 10 mg of extended-release oxybutynin (OER). The study protocol and design were identical for the two trials and site selection ensured that there was no bias in either trial for the tendency of investigators to prescribe one drug rather than the other, or for geographical location. A total of 1289 patients were enrolled, 669 in the tolterodine trial (TER 2 mg, n = 333; TER 4 mg, n = 336) and 620 in the oxybutynin trial (OER 5 mg, n = 313; OER 10 mg, n = 307). Fewer patients prematurely withdrew from the trial in the TER 4 mg group (12%) than either the OER 5 mg (19%; p = 0.01) or OER 10 mg groups (21%; p = 0.002). More patients in the OER 10 mg group than the TER 4 mg group withdrew because of poor tolerability (13% vs 6%; p = 0.001). After 8 weeks, 70% of patients in the TER 4 mg group perceived an improved bladder condition, compared with 60% in the TER 2 mg group, 59% in the OER 5 mg group and 60% in the OER 10 mg group (all p < 0.01 vs TER 4 mg). Response to therapy was greater in a subgroup of patients whose perception of bladder condition was moderate to severe at baseline (TER 4 mg 77% vs OER 10 mg 65%; p < 0.01). Dry mouth was dose-dependent with both agents, although differences between doses only reached statistical significance in the oxybutynin trial (OER 5 mg vs OER 10 mg; p = 0.05). Patients treated with TER 4 mg reported a significantly lower severity of dry mouth compared with OER 10 mg. In conclusion, the greater efficacy and tolerability of tolterodine ER 4 mg suggests improved clinical effectiveness compared with oxybutynin ER 10 mg.

Topics: Adult; Aged; Analysis of Variance; Benzhydryl Compounds; Cholinergic Antagonists; Cresols; Delayed-Action Preparations; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urination

The objective of the present study was to examine the long-term safety, tolerability and efficacy of tolterodine extended-release (ER) in patients who had completed 12 weeks' treatment in a randomised, double-blind study comparing tolterodine ER 4 mg once daily (qd), tolterodine immediate-release (IR) 2mg twice daily and placebo.. Of the 1377 patients completing the 12-week study, a total of 1077 (78%) chose to continue with 12 months' open-label treatment with tolterodine ER 4 mg once daily, irrespective of their previous treatment. Safety was assessed after 3, 6, 9 and 12 months' treatment in the study. Efficacy was evaluated from micturition diary variables and patients' perception of bladder condition and urgency following 3 and 12 months' treatment.. 71% of patients completed the 12-month study. Tolterodine ER was safe and well tolerated. Adverse events of the general (14.5%), autonomic (13.2%), gastrointestinal (11.4%), respiratory (9.8%) and urinary (9.1%) systems were the most frequently reported. Dry mouth was the most common event, occurring in 12.9% of patients, and was generally mild in severity. Other adverse events occurred in less than 5% of patients. There was no increase in the frequency of adverse events with long-term relative to short-term treatment. The efficacy of tolterodine was maintained over the 12-month treatment period; relative to baseline there were reductions in the number of incontinence episodes per week (median change -83%) and micturitions per 24 hours (median change -21%) and an increase in volume voided (median change +25%) after 12 months' treatment. An improvement in patient perception of their bladder condition was found in 75% of patients completing the study, and 51% had an improvement in patient perception of urgency.. Tolterodine ER 4mg qd displayed a favourable safety, tolerability and efficacy profile during 12 months' treatment of patients with overactive bladder.

Topics: Adult; Aged; Aged, 80 and over; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic

To compare the efficacy and tolerability of extended-release oxybutynin chloride and tolterodine tartrate at 12 weeks in participants with overactive bladder.. The OBJECT (Overactive Bladder: Judging Effective Control and Treatment) study was a prospective, randomized, double-blind, parallel-group study conducted between March and October 2000 at 37 US study sites. Participants who had between 7 and 50 episodes of urge incontinence per week and 10 or more voids in 24 hours received extended-release oxybutynin, 10 mg/d, or tolterodine, 2 mg twice daily. The outcome measures were the number of episodes of urge incontinence, total incontinence, and micturition frequency at 12 weeks adjusted for baseline.. A total of 315 women and 63 men were randomized and treated, and 332 participants (276 women, 56 men) completed the study. At the end of the study, extended-release oxybutynin was significantly more effective than tolterodine in each of the main outcome measures: weekly urge incontinence (P=.03), total incontinence (P=.02), and micturition frequency episodes (P=.02) adjusted for baseline. Both drugs improved symptoms of overactive bladder significantly from baseline to the end of the study as assessed by the 3 main outcome measures (P<.001). Dry mouth, the most common adverse event, was reported by 28.1% and 33.2% of participants taking extended-release oxybutynin and tolterodine, respectively (P=.32). Rates of central nervous system and other adverse events were low and similar in both groups.. Extended-release oxybutynin was more effective than tolterodine as measured by end-of-study urge incontinence, total incontinence, and micturition frequency episodes. Both groups had similar rates of dry mouth and other adverse events.

Topics: Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Nervous System Diseases; Phenylpropanolamine; Probability; Prospective Studies; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Tartrates; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Incontinence, Stress; Urination Disorders; Xerostomia

We compared the tolerability and clinical efficacy of tolterodine with those of oxybutynin in patients with an overactive bladder using an upward oxybutynin dose titration strategy analogous to that used in routine clinical practice in the United Kingdom and Republic of Ireland.. In a randomized double-blind trial 378 male and female patients 50 years old or older with symptoms of overactive bladder (a urinary frequency of 8 or more voids per 24 hours with urgency and/or urge incontinence, that is 1 or more urge incontinence episodes per 24 hours) received 10 weeks of treatment with 2 mg. tolterodine twice daily/or an initial dose of 2.5 mg. oxybutynin twice daily, increasing to 5 mg. twice daily after 2 weeks of treatment. The main outcome measures were changes in voiding diary variables combined with detailed tolerability-safety assessments.. Patients treated with tolterodine had significantly fewer adverse events (69% versus 81%, p = 0.01), notably dry mouth (37% versus 61%, p <0.0001), as well as a lower incidence of dose reduction (6% versus 25%, p <0.0001) than those in the oxybutynin group. Each agent had comparable efficacy for improving urinary symptoms. Tolterodine and oxybutynin caused a significant decrease (p = 0.0001) in the mean number of voids per 24 hours (-1.7 or -15% and -1.7 or -15%, respectively), urge incontinence episodes per 24 hours (-1.3 or -54% and -1.8 or -62%, respectively) and mean voided volume per void (33 ml. or 22% and 34 ml. or 23%) after 10 weeks of treatment.. Tolterodine is as effective as oxybutynin for improving the symptoms of overactive bladder but it has superior tolerability. The combination of these qualities makes tolterodine the preferred pharmacological therapy for the long-term treatment of this condition.

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

To investigate the urodynamic effects and tolerability of the new antimuscarinic drug tolterodine in children with detrusor hyperreflexia.. Twenty-two children (12 boys and 10 girls; age range 3 months to 15 years, mean age 5.7 years) with detrusor hyperreflexia resulting in maximum detrusor pressures exceeding 40 cm H(2)O during filling cystotonometry were enrolled to receive tolterodine tartrate (a total of 0.1 mg/kg orally daily, divided into two doses) either as a first-line therapy (n = 12, group 1) or replacing oxybutynin chloride therapy (n = 10, group 2). Within 3 months, all patients underwent urodynamic re-evaluation during ongoing tolterodine treatment.. In group 1, the mean maximum bladder capacity increased from 120.2 to 173.0 mL (+44%), the mean detrusor compliance increased from 8.7 to 13.5 mL/cm H(2)O (+55%), and the mean maximum detrusor pressures decreased from 70.1 to 37.9 cm H(2)O (-46%); the differences were significant (P < 0.001). In group 2, no differences in the urodynamic effects of oxybutynin versus tolterodine were noted. Only 1 patient experienced a transient and moderately adverse effect with tolterodine.. Although based on a limited number of subjects, these data indicate that in pediatric patients with detrusor hyperreflexia, tolterodine may be better tolerated than and equally effective as the standard drug oxybutynin chloride.

Topics: Adolescent; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Female; Humans; Infant; Male; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urodynamics

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

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

Pediatric drug development is challenging when a product is studied for a pediatric disease that has a different underlying etiology and pathophysiology compared to the adult disease. Neurogenic bladder dysfunction (NBD) is such a therapeutic area with multiple unsuccessful development programs. The objective of this study was to critically evaluate clinical trial design elements that may have contributed to unsuccessful drug development programs for pediatric NBD. Trial design elements of drugs tested for pediatric NBD were identified from trials submitted to the U.S. Food and Drug Administration. Data were extracted from publically available FDA reviews and labeling and included trial design, primary endpoints, enrollment eligibilities, and pharmacokinetic data. A total of four products were identified. Although all four programs potentially provided clinically useful information, only one drug (oxybutynin) demonstrated efficacy in children with NBD. The lack of demonstrable efficacy for the remainder of the products illustrates that future trials should give careful attention to testing a range of doses, using objectively measured, clinically meaningful endpoints, and selecting clinical trial designs that are both interpretable and feasible. Compiling the drug development experience with pediatric NBD will facilitate an improved approach for future drug development for this, and perhaps other, therapeutic areas.

Topics: Adolescent; Adrenergic alpha-1 Receptor Antagonists; Area Under Curve; Benzhydryl Compounds; Child; Child, Preschool; Cresols; Delayed-Action Preparations; Humans; Infant; Mandelic Acids; Marine Toxins; Muscarinic Antagonists; Oxocins; Phenylpropanolamine; Quinazolines; Tablets; Tolterodine Tartrate; Urinary Bladder, Neurogenic

To evaluate the efficacy of extended-release (ER) tolterodine 4mg/day for the treatment of neurogenic detrusor overactivity (NDO) and/or low-compliance bladder by assessing urodynamic parameters.. Forty-six patients (25 male, 21 female; mean age 57.6±20.7years) with NDO (n=39) and/or low-compliance bladder (n=7) were included in this 12-week single-arm study. Twenty-one patients (46%) were on clean intermittent catheterization and other patients could void on their own. A video urodynamic study was performed before and at 3 months after treatment. Changes in Overactive Bladder Symptom Score (OABSS), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and King's Health Questionnaire (KHQ) as well as changes in number of voids, amount of each void, and number of leaks in 24h according to the 3-day voiding diary were also evaluated before treatment and at weeks 4 and 12 after treatment.. Bladder capacity at first sensation and maximum cystometric capacity increased significantly, by an average of 36.8mL (P=0.0402) and 82.3mL (P<0.0001), respectively. Maximum cystometric capacity increased by more than 50mL in 19 patients (49%) following treatment. Detrusor overactivity disappeared in three of 32 patients (9%), bladder capacity at first involuntary contraction increased significantly (P=0.0009), and amplitude of detrusor overactivity decreased significantly (P=0.0025). In patients with low-compliance bladder, bladder compliance increased significantly (P=0.0156). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire-Short Form score, number of voids (per 24h and night-time), number of urgency episodes in 24h, number and amount of leaks in 24h, and amount of mean and maximum voided volumes all decreased significantly after treatment.. Tolterodine is effective and well tolerated for the treatment of NDO and/or low-compliance bladder in patients with neurogenic bladder.

Topics: Adult; Aged; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Prospective Studies; Quality of Life; Statistics, Nonparametric; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive; Urodynamics

We investigated the effects of standard oral anticholinergic treatment with tolterodine in children with neurogenic bladder over a 5-year follow-up period and focused on treatment satisfaction, patient compliance and urodynamic parameters.. The follow-up consisted of regular visits and urodynamic evaluation at least once a year. The patients or their parents were interviewed to evaluate voiding behavior, as well as factors leading to lower patient compliance and deterioration in urodynamic parameters.. Of the 43 patients evaluated, 30 (70%) took their anticholinergic medication consistently and 13 (30%) sporadically. The mean bladder capacity was 354.7 ml in the first group but only 214.7 ml in the noncompliant group (p < 0.001). The mean maximal detrusor pressure decreased from 42.2 to 33.6 cm H(2)O in the compliant group (p < 0.001) and from 49.7 to 46.4 cm H(2)O in the noncompliant group (p = 0.21). The mean detrusor compliance increased from 18.9 to 19.3 ml/cm H(2)O in the compliant group (p = 0.63) and from 11.8 to 12.3 ml/cm H(2)O in the noncompliant group (p = 0.87). Side effects such as dry mouth (11/13) and dizziness (7/13) were common in the noncompliant group, whereas only 5/30 reported dry mouth in the compliant group.. These data demonstrate the efficacy and tolerability of tolterodine over a long follow-up period. The results are promising in view of the fact that the patients will probably require life-long medication. Nevertheless, anticholinergic side effects still cause some patients to refuse regular medication, which results in a poorer urodynamic outcome.

Topics: Benzhydryl Compounds; Child; Cresols; Female; Follow-Up Studies; Humans; Male; Muscarinic Antagonists; Patient Compliance; Phenylpropanolamine; Time Factors; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Bladder, Overactive

Solifenacin succinate [YM905, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a novel muscarinic receptor antagonist. We examined the effects of solifenacin and two other muscarinic receptor antagonists, tolterodine and propiverine, on detrusor overactivity in cerebral infarcted rats. Evaluation was done under conscious conditions using cystometry 1 day after middle cerebral artery occlusion. The cerebral infarcted rats showed decreases in bladder capacity and voided volume and an increase in residual volume, but no change in micturition pressure. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.

Topics: Animals; Benzhydryl Compounds; Benzilates; Cresols; Infarction, Middle Cerebral Artery; Male; Muscarinic Antagonists; Muscle, Smooth; Phenylpropanolamine; Quinuclidines; Rats; Rats, Sprague-Dawley; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder, Neurogenic

The etiologies and forms of congenital neuropathic bladder are described: contractile (25%), acontractile (15%), and intermediate (60%). The terminology relating to neuropathic bladder is defined and the principles of bladder management are highlighted: (1) must achieve a bladder that can fill at low pressure, (2) must achieve a bladder that can store urine at low pressure, (3) must achieve sphincter resistance that is sufficient to allow urine storage, and (4) must put in place a mechanism of achieving complete voluntary bladder emptying. The approach to investigation is set out in a logical sequence, and the methods of achieving the goals highlighted above are described. All of this is put in the context of managing the handicapped patient as a whole. It also is stressed that the aim is not just to achieve continence but perhaps even more importantly to protect renal function.

Topics: Benzhydryl Compounds; Child; Child, Preschool; Cholinergic Antagonists; Cresols; Female; Humans; Infant; Male; Mandelic Acids; Meningomyelocele; Muscarinic Antagonists; Phenylpropanolamine; Tolterodine Tartrate; Urinary Bladder, Neurogenic; Urinary Catheterization