title: Pharmacokinetics and pharmacodynamics of tolterodine in man: a new drug for the treatment of urinary bladder overactivity. Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of tolterodine Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder. Prospective, randomized, double-blind study of the efficacy and tolerability of the extended-release formulations of oxybutynin and tolterodine for overactive bladder: results of the OPERA trial. Tolterodine in the treatment of overactive bladder: analysis of the pooled phase II efficacy and safety data. Multiple Dose Pharmacokinetics of a New Once Daily Extended Release Tolterodine Formulation Versus Immediate Release Tolterodine Differential Pharmacological Effects of Antimuscarinic Drugs on Heart Rate: A Randomized, Placebo-controlled, Double-blind, Crossover Study With Tolterodine and Darifenacin in Healthy Participants ≥50 Years Tolterodine and tamsulosin for treatment of men with lower urinary tract symptoms and overactive bladder: a randomized controlled trial. Tolterodine, a new antimuscarinic agent: as effective but better tolerated than oxybutynin in patients with an overactive bladder. Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder. Tolterodine: a safe and effective treatment for older patients with overactive bladder. Tolterodine treatment improves storage symptoms suggestive of overactive bladder in men treated with alpha-blockers. Population-based survey of urinary incontinence, overactive bladder, and other lower urinary tract symptoms in five countries: results of the EPIC study. Combination treatment with an alpha-blocker plus an anticholinergic for bladder outlet obstruction: a prospective, randomized, controlled study. A comparison of the efficacy and tolerability of solifenacin succinate and extended release tolterodine at treating overactive bladder syndrome: results of the STAR trial. Results of a randomized phase III trial of mirabegron in patients with overactive bladder.
abstract: The aim of this study was to determine the pharmacokinetics , pharmacodynamics , and safety of tolterodine following single oral and intravenous doses in healthy volunteers . A secondary aim was to identify major urinary metabolites and determine mass balance . Single oral doses of 0.2 , 0.4 , 0.8 , 1.6 , 3.2 , 6.4 , and 12.8 mg of tolterodine ( as the tartrate salt ) were given to 17 healthy male volunteers . Two intravenous doses ( 0.64 and 1.28 mg ) were administered to 8 of the volunteers and mass balance was studied after a single oral dose of 5 mg (14C)-tolterodine in 6 subjects . Tolterodine was rapidly absorbed following oral administration ( time to peak serum concentration 0.9 + /- 0.4 h ) . The absolute bioavailability was highly variable , ranging from 10 to 70 % . The volume of distribution at steady-state ranged from 0.9 to 1.6 l/kg and systemic clearance ranged from 0.23 to 0.52 l/h/kg , which result ed in a terminal half-life of 2 - 3 h. Tolterodine exhibited high first-pass metabolism and 2 hepatic metabolic pathways were identified : oxidation and dealkylation . Independent of route of administration , < 1 % of the parent compound was excreted unchanged in urine . Five metabolites were structurally identified in urine . Following oral administration of (14C)-tolterodine , the excretion of radioactivity into urine and feces was 77 + /- 4.0 % and 17 + /- 3.5 % , respectively . Tolterodine decreased stimulated salivation after 3.2 mg , increased heart rate after 6.4 mg , and nearpoint of vision after 12.8 mg . Six of 8 subjects reported micturition difficulties after a dose of 12.8 mg . The lack of a direct relationship between tolterodine  serum concentrations and effects on stimulated salivation suggested the presence of pharmacologically active metabolite(s ) To determine whether cytochrome P450 2D6 ( CYP2D6 ) is involved in the metabolism of tolterodine by investigating potential differences in pharmacokinetics and pharmacodynamics ( heart rate , accommodation , and salivation ) of tolterodine and its 5‐hydroxymethyl metabolite between poor metabolizers and extensive metabolizers of debrisoquin ( INN , debrisoquine ) OBJECTIVES To evaluate the efficacy and tolerability of a new extended-release ( ER ) , once-daily , capsule formulation of tolterodine , relative to placebo and the existing immediate-release ( IR ) , twice-daily , tablet formulation , for treatment of the overactive bladder . METHODS This was a double-blind , multicenter , r and omized , placebo-controlled trial . One thous and 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 r and omized to oral therapy with tolterodine ER 4 mg once daily ( n = 507 ) , tolterodine IR 2 mg twice daily ( n = 514 ) , or placebo ( n = 508 ) for 12 weeks . Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables . Tolerability and safety were assessed by evaluating the adverse events , electrocardiogram parameters , laboratory values , and treatment withdrawals . RESULTS Tolterodine ER 4 mg once daily ( P = 0.0001 ) and tolterodine IR 2 mg twice daily ( P = 0.0005 ) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo . The median reduction in these episodes as a percentage of the baseline values was 71 % for tolterodine ER , 60 % for tolterodine IR , and 33 % for placebo . The ER formulation was 18 % more effective than the IR formulation ( P < 0.05 ) . Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo . For both formulations , the mean decreases in micturition frequency ( P < 0.0079 ) and pad usage ( P < 0.0145 ) were significant , and the mean volume voided per micturition increased ( P = 0.0001 ) . The rate of dry mouth ( of any severity ) was 23 % for tolterodine ER , 30 % for tolterodine IR , and 8 % for placebo . The overall dry mouth rate for patients taking tolterodine ER was 23 % lower than for tolterodine IR ( P < 0.02 ) , and the rate of severe dry mouth in the ER group was only 1.8 % . The rates of withdrawal were comparable for the two active groups and the placebo group . No safety concerns were noted . CONCLUSIONS Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns . Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation OBJECTIVE To compare the efficacy and tolerability of extended-release formulations of oxybutynin chloride and tolterodine tartrate in women with overactive bladder . PATIENTS AND METHODS The OPERA ( Overactive bladder : Performance of Extended Release Agents ) trial was a r and omized , 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 . RESULTS 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 . CONCLUSIONS 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 OBJECTIVES To summarize the efficacy and safety of tolterodine from the pooled data of four multicenter , r and omized , double-blind , placebo-controlled , dose-ranging , parallel-group Phase II studies in patients with urodynamically proved overactive bladder ( detrusor instability or detrusor hyperreflexia ) and to analyze the concentration-effect relation . METHODS After a 1-week run-in period to establish baseline values , 319 patients were r and omized to receive  placebo or tolterodine  0.5 , 1 , 2 , or 4 mg twice daily . Micturition diary and urodynamic variables and subjective urinary symptoms were assessed after 2 weeks of treatment . Patients were classified as " extensive " or " poor " metabolizers of tolterodine on the basis of serum levels of tolterodine . RESULTS A per- protocol analysis of efficacy in 262 patients showed dose-related improvements in micturition diary and urodynamic variables . A dosage of 4 mg twice daily was , however , associated with an increase in residual urinary volume . The incidence of adverse events ( mainly mild or moderate antimuscarinic effects ) was comparable between placebo and tolterodine dosages of 2 mg twice daily . No serious drug-related adverse events were observed , and tolterodine had no clinical ly significant impact on electrocardiographic or laboratory findings . Changes in urodynamic variables were found to be related to the sum of unbound serum concentrations of  tolterodine  and its major active 5-hydroxymethyl metabolite . In poor and extensive metabolizers of tolterodine , exposure to the sum of these active moieties was similar , and the efficacy and safety profiles were comparable . CONCLUSIONS The results of this pooled data analysis indicate that tolterodine offers an effective treatment for patients with urinary symptoms attributable to overactive bladder . The optimal dosage is 1 to 2 mg twice daily , irrespective of metabolic phenotype Objective To determine the multiple dose pharmacokinetics of a new extended release ( ER ) capsule formulation of tolterodine , compared with the existing immediate release ( IR ) tablet , in healthy volunteers . Design Nonblind , r and omised , 2-way crossover trial . Participants 19 healthy volunteers ( 7 females , 12 males ) , mean age 33 years ( range 18 to 55 years ) . Prior to the study , all volunteers were classified as either extensive or poor metabolisers by cytochrome P450 2D6 genotyping . Methods Volunteers received tolterodine ER 4 mg once daily or tolterodine IR 2 mg twice daily for 6 days ( all doses given as the L-tartrate salt ) . A washout period of 7 days separated the 2 treatments . Serum concentrations of tolterodine , its active 5-hydroxymethyl metabolite ( 5-HM ) and the active moiety ( extensive metabolisers : sum of unbound tolterodine + 5-HM ; poor metabolisers : unbound tolterodine ) were measured for up to 48 hours post-dose on day 6 ( steady state ) . Tolerability was also determined . Results 17 volunteers ( 13 extensive metabolisers , 4 poor metabolisers ) completed the study and were evaluable for both treatment periods . The 90 % confidence interval for the geometric mean ratio of area under the serum concentration-time curve to 24 hours ( AUC24 ) of the active moiety , for all volunteers combined , indicated equivalence for the 2 formulations . Pooled analysis also demonstrated that the peak serum concentration ( Cmax ) of the active moiety following administration of tolterodine ER was around 75 % of that observed for the IR tablet , whereas the trough concentration was around 1.5-fold higher . Overall , the pharmacokinetics of tolterodine ( irrespective of genotype ) and 5-HM ( extensive metabolisers only ) were consistent with sustained drug release over 24 hours .  Tolterodine  ER was well tolerated . Conclusions The new once daily ER formulation of tolterodine 4 mg shows pharmacokinetic equivalence ( AUC24 ) to the existing IR tablet given at a dose of 2 mg twice daily . Findings of lower Cmax for  tolterodine  ER may explain the significantly lower rate of dry mouth subsequently observed in patients with overactive bladder Antimuscarinics , used commonly to treat overactive bladder , may differ in their potential to increase heart rate via effects on cardiac muscarinic M2 receptors . This prospect i ve , 3-way crossover , r and omized , double-blind study assessed the heart rate effects of 7 days ' exposure to a nonselective M2/M3 receptor blocker ( tolterodine ; 4 mg/d ) , a highly selective M3 receptor blocker ( darifenacin ; 15 mg/d ) , and placebo in 162 healthy participants ≥50 years . Heart rate was measured by 24-hour Holter monitoring . Tolterodine significantly increased heart rate versus darifenacin and heart rate versus placebo , while darifenacin did not affect heart rate versus placebo . The proportion of participants with an increase in mean heart rate per 24 hours of ≥5 beats per minute was higher with tolterodine than with darifenacin ( P = .0004 ) or with placebo ( P = .0114 ) but did not differ between darifenacin and placebo . The results show that antimuscarinics exert differential effects on heart rate depending on their muscarinic receptor profile . This should be considered when selecting a treatment CONTEXT Men with overactive bladder and other lower urinary tract symptoms may not respond to monotherapy with antimuscarinic agents or alpha-receptor antagonists . OBJECTIVE To evaluate the efficacy and safety of tolterodine extended release ( ER ) , tamsulosin , or both in men who met research criteria for both overactive bladder and benign prostatic hyperplasia . DESIGN , SETTING , AND PARTICIPANTS R and omized , double-blind , placebo-controlled trial conducted at 95 urology clinics in the United States involving men 40 years or older who had a total International Prostate Symptom Score of 12 or higher and , an International Prostate Symptom Score quality -of-life ( QOL ) item score of 3 or higher , a self-rated bladder condition of at least moderate bother , and a bladder diary documenting micturition frequency ( > or=8 micturitions per 24 hours ) and urgency ( > or=3 episodes per 24 hours ) , with or without urgency urinary incontinence . Patients were recruited between November 2004 and February 2006 , and the study was completed May 2006 . INTERVENTIONS Patients were r and omly assigned to receive placebo ( n = 222 ) , 4 mg of tolterodine ER ( n = 217 ) , 0.4 mg of tamsulosin ( n = 215 ) , or both tolterodine ER plus tamsulosin ( n = 225 ) for 12 weeks . MAIN OUTCOME MEASURES Patient perception of treatment benefit , bladder diary variables , International Prostate Symptom Scores , and safety and tolerability were assessed . RESULTS A total of 172 men ( 80 % ) receiving tolterodine ER plus tamsulosin reported treatment benefit by week 12 compared with 132 patients ( 62 % ) receiving placebo ( P<.001 ) , 146 ( 71 % ) receiving tamsulosin ( P=.06 vs placebo ) , or 135 ( 65 % ) receiving tolterodine ER ( P=.48 vs placebo ) . Patients receiving tolterodine ER plus tamsulosin compared with placebo experienced significant reductions in urgency urinary incontinence ( -0.88 vs -0.31 , P=.005 ) , urgency episodes without incontinence ( -3.33 vs -2.54 , P=.03 ) , micturitions per 24 hours ( -2.54 vs -1.41 , P<.001 ) , and micturitions per night ( -0.59 vs -0.39 , P.02 ) . Patients receiving tolterodine ER plus tamsulosin demonstrated significant improvements on the total International Prostate Symptom Score ( -8.02 vs placebo , -6.19 , P=.003 ) and QOL item ( -1.61 vs -1.17 , P=.003 ) . All interventions were well tolerated . The incidence of acute urinary retention requiring catheterization was low ( tolterodine ER plus tamsulosin , 0.4 % ; tolterodine ER , 0.5 % ; tamsulosin , 0 % ; and placebo , 0 % ) . CONCLUSIONS These results suggest that treatment with tolterodine ER plus tamsulosin for 12 weeks provides benefit for men with moderate to severe lower urinary tract symptoms including overactive bladder . Clinical Trials Registration clinical trials.gov Identifier : NCT00147654 OBJECTIVE To compare the efficacy and tolerability of tolterodine with that of oxybutynin in patients with an overactive bladder . PATIENTS AND METHODS A r and omized , double-blind , placebo-controlled , parallel group , multinational phase-III study was conducted in urology and gynaecology clinics in the UK , Republic of Irel and and Sweden . The study enrolled 293 patients with urodynamically confirmed bladder overactivity , increased frequency of micturition ( > or = micturitions/24 h ) and symptoms of urgency and /or urge incontinence ( > or = 1 episode/24 h ) . Patients received either tolterodine ( 2 mg twice daily ) or oxybutynin ( 5 mg three times daily ) or placebo . Doses could be reduced , to prevent withdrawal , to 1 mg or 2.5 mg , respectively . The main outcome measures were the mean change from baseline in frequency of micturition/24 h , the number of incontinent episodes/24 h and volume voided per micturition . RESULTS After 12 weeks ' treatment , the mean frequency of micturition decreased by 21 % and 19.5 % in those receiving tolterodine ( n = 118 ) and oxybutynin ( n = 118 ) , respectively , and by 10.5 % in those on placebo ( n = 57 ) . Among those with urge incontinence at baseline ( 75 % of patients ) , the mean number of incontinent episodes decreased by 47 % , 71 % and 19 % , respectively , in those receiving tolterodine , oxybutynin and placebo . The effect of tolterodine and oxybutynin on these two micturition variables was statistically equivalent . There was also a comparable increase in mean volume voided per micturition in the tolterodine ( 27 % ) and oxybutynin groups ( 31 % ) , compared with 7 % in the placebo group . Dry mouth was the most common adverse event and was reported with greater frequency and intensity among patients receiving oxybutynin than among those receiving either tolterodine or placebo . In the oxybutynin group , more patients also withdrew because of adverse events and a greater proportion required dose reduction as a result of adverse events . Despite dose reduction , the frequency of adverse events and the intensity of dry mouth remained higher among those receiving oxybutynin ( 2.5 mg three times daily ) than in patients who remained on tolterodine 2 mg twice daily . CONCLUSION Tolterodine 2 mg twice daily is effective and well tolerated in the treatment of bladder overactivity .  Tolterodine was better tolerated than oxybutynin , particularly with respect to the frequency and intensity of dry mouth , but had comparable clinical efficacy . The superior tolerability of tolterodine therefore allows more patients to remain on effective therapy than the current most commonly prescribed agent for the treatment of the overactive bladder OBJECTIVE To determine the efficacy , tolerability , and safety of fesoterodine in subjects with overactive bladder ( OAB ) . METHODS This was a multicentre , r and omised , 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 r and omised 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 . RESULTS At the end of treatment , subjects taking fesoterodine 4 and 8 mg had significant ( p<0.05 ) and clinical ly 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 . CONCLUSIONS 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 OBJECTIVE To investigate the clinical safety and efficacy of two dosages of tolterodine in older patients with symptoms attributable to overactive bladder . DESIGN R and omized , double-blind , placebo-controlled , parallel-group , multinational , phase III study . SETTING Incontinence , older care , urological , and urogynecological clinics in the United Kingdom , France , and the Republic of Irel and . PARTICIPANTS 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 ) . INTERVENTION Tolterodine 1 mg or 2 mg twice daily ( bid ) , or placebo , for 4 weeks . MEASUREMENTS 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 . RESULTS 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 . CONCLUSION 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 BACKGROUND Some men receiving alpha-blocker therapy for lower urinary tract symptoms report persistent storage symptoms suggestive of overactive bladder ( OAB ) . OBJECTIVE To evaluate the efficacy of tolterodine extended release ( ER ) in men on alpha-blocker therapy . DESIGN , SETTING , AND PARTICIPANTS This double-blind trial included men aged > or = 40 yr with frequency , urgency , and at least moderate problems reported on the Patient Perception of Bladder Condition ( PPBC ) , despite being on a stable dose of alpha-blocker for > or = 1 mo . INTERVENTIONS Subjects were r and omized to tolterodine ER 4 mg per day or placebo for 12 wk while continuing their prescribed alpha-blocker therapy . MEASUREMENTS At baseline and week 12 , subjects completed the PPBC , International Prostate Symptom Score ( IPSS ) , Overactive Bladder Question naire ( OAB-q ) , and 5-d bladder diaries using the five-point Urinary Sensation Scale ( USS ) . Frequency-urgency sum was defined as the sum of USS ratings for all micturitions . RESULTS AND LIMITATIONS PPBC improvement from baseline to week 12 was reported by 63.6 % and 61.6 % of subjects receiving tolterodine ER plus alpha-blocker and placebo plus alpha-blocker , respectively ; this treatment difference , which was the primary end point , was not statistically significant ( p>0.6699 ) . At week 12 , subjects receiving tolterodine ER plus alpha-blocker had significantly greater improvements versus placebo plus alpha-blocker in 24-h micturitions ( -1.8 vs -1.2 ; p=0.0079 ) and daytime micturitions ( -1.3 vs -0.8 ; p=0.0123 ) ; 24-h urgency episodes ( -2.9 vs -1.8 ; p=0.0010 ) , daytime urgency episodes ( -2.2 vs -1.4 ; p=0.0017 ) , and nocturnal urgency episodes ( -0.5 vs -0.3 ; p=0.0378 ) ; frequency-urgency sum ( -7.8 vs -5.1 ; p=0.0065 ) ; IPSS storage subscale ( -2.6 vs -2.1 ; p=0.0370 ) ; and OAB-q symptom bother scale ( -17.9 vs -14.4 ; p=0.0086 ) and coping domain ( 15.4 vs 12.4 ; p=0.0491 ) . Acute urinary retention requiring catheterization occurred in < 1 % of either group . There were no clinical ly meaningful changes in postvoid residual volume or maximum urinary flow rate .  CONCLUSIONS Men with bothersome OAB symptoms despite continued alpha-blocker therapy showed significantly greater improvements in diary variables , IPSS Storage scores , and symptom bother when receiving additional tolterodine ER versus placebo plus alpha-blocker OBJECTIVE Estimate the prevalence of urinary incontinence ( UI ) , overactive bladder ( OAB ) , and other lower urinary tract symptoms ( LUTS ) among men and women in five countries using the 2002 International Continence Society ( ICS ) definitions . METHODS This population -based , cross-sectional survey was conducted between April and December 2005 in Canada , Germany , Italy , Sweden , and the United Kingdom using computer-assisted telephone interviews .  A r and om sample of men and women aged > /= 18 yr residing in the five countries and who were representative of the general population s in these countries was selected . Using 2002 ICS definitions , the prevalence estimates of storage , voiding , and postmicturition LUTS were calculated . Data were stratified by country , age cohort , and gender . RESULTS A total of 19,165 individuals agreed to participate ; 64.3 % reported at least one LUTS . Nocturia was the most prevalent LUTS ( men , 48.6 % ; women , 54.5 % ) . The prevalence of storage LUTS ( men , 51.3 % ; women , 59.2 % ) was greater than that for voiding ( men , 25.7 % ; women , 19.5 % ) and postmicturition ( men , 16.9 % ; women , 14.2 % ) symptoms combined . The overall prevalence of OAB was 11.8 % ; rates were similar in men and women and increased with age . OAB was more prevalent than all types of UI combined ( 9.4 % ) . CONCLUSIONS The EPIC study is the largest population -based survey to assess prevalence rates of OAB , UI , and other LUTS in five countries . To date , this is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions . The results indicate that these symptoms are highly prevalent in the countries surveyed PURPOSE We evaluate the effect of tolterodine combined with tamsulosin on quality of life in patients with bladder outlet obstruction and concomitant detrusor instability . MATERIAL S AND METHODS The study included 50 consecutive patients with urodynamically proven mild or moderate bladder outlet obstruction and concomitant detrusor instability . All patients were initially treated with 0.4 mg . tamsulosin orally once a day . A week later the patients were r and omly allocated into group 1 - 25 who continued treatment with tamsulosin only and , group 2 - 25 who also received 2 mg . tolterodine orally twice daily . Reevaluation with a quality of life question naire and urodynamic study was performed after 3 months . RESULTS Two patients from group 2 stopped tolterodine while 1 patient from each group stopped tamsulosin because of hypotension . Analysis revealed statistically significant improvement in quality of life scores only in group 2 patients ( mean score 525.0 and 628.4 before and after treatment , respectively , 2-sided t test p = 0.0003 ) . A significant difference was noted in both groups after treatment for maximum flow rate and volume at first contraction . Additionally , in group 2 , a statistically significant difference was observed for maximum detrusor pressure and maximum unstable contraction pressure after treatment . CONCLUSIONS Combination treatment with an alpha-blocker ( tamsulosin ) plus an anticholinergic ( tolterodine ) improves quality of life in patients with bladder outlet obstruction and concomitant detrusor instability . Interestingly , no acute urinary retention was observed and tolterodine did not affect the quality of urine flow or residual urine volume . The proposed combination appears to be an effective and relatively safe treatment option in patients with bladder outlet obstruction and detrusor instability OBJECTIVE To compare two new generation antimuscarinics at their recommended doses for treatment of overactive bladder syndrome ( OAB ) . METHODS A prospect i ve , 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 . RESULTS 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 assessment s. The majority of side effects were mild to moderate in nature , and discontinuations were comparable and low in both groups . CONCLUSIONS Solifenacin , with a flexible dosing regimen , was found to be superior to tolterodine ER with respect to the majority of the efficacy variables PURPOSE Many patients with overactive bladder discontinue pharmacotherapy due to suboptimal efficacy or side effects . Mirabegron , a β3-adrenoceptor agonist , may offer an effective and well tolerated alternative treatment for overactive bladder . MATERIAL S AND METHODS A r and omized , double-blind , placebo controlled trial was conducted in the United States and Canada . After a 2-week placebo run-in period , adults with overactive bladder symptoms for 3 or more months were r and omized 1:1:1 to receive placebo , 50 or 100 mg mirabegron once daily for 12 weeks . Efficacy data were collected via patient completed diaries and quality of life assessment s. Co- primary efficacy end points were changes from baseline to final visit in mean number of incontinence episodes per 24 hours and micturitions per 24 hours . Key secondary micturition and incontinence end points were also evaluated . Safety assessment s included treatment emergent adverse events , laboratory assessment s , vital signs , electrocardiograms and post-void residual volume . RESULTS Compared to placebo , 50 and 100 mg mirabegron groups demonstrated statistically significantly greater mean decreases ( 95 % CI ) from baseline for incontinence episodes ( -1.13 [ -1.35 , -0.91 ] , -1.47 [ -1.69 , -1.25 ] and -1.63 [ -1.86 , -1.40 ] ) and micturitions ( -1.05 [ -1.31 , -0.79 ] , -1.66 [ -1.92 , -1.40 ] and -1.75 [ -2.01 , -1.48 ] ) per 24 hours ( p < 0.05 ) . Significant improvements in all key secondary end points were observed for both mirabegron doses vs placebo . The incidence of frequently reported treatment emergent adverse events ( hypertension , urinary tract infection , headache , nasopharyngitis ) was similar in the mirabegron and placebo groups . Dry mouth was reported for 1.5 % , 0.5 % and 2.1 % of patients in the placebo , 50 and 100 mg mirabegron groups , respectively . CONCLUSIONS Once daily mirabegron in a 50 or 100 mg dose is an effective treatment for overactive bladder symptoms with a low occurrence of side effects
target: The efficacy and tolerability of tolterodine ER Vs .
  A recent meta- analysis evaluating tolterodine in comparison with other antimuscarinic drugs demonstrated that tolterodine ER was significantly more effective than placebo in reducing micturition/24 h , urinary leakage episodes/24 h , urgency episodes/24 h , and urgency incontinence episodes/24 h. With regard to adverse events , tolterodine ER was associated with a good adverse event profile result ing in the third most favorable antimuscarinic .
  Conclusion Tolterodine ER result ed effective in reducing frequency urgency and nocturia and urinary leakage in male patients with OAB/storage LUTS .
  Dry mouth and constipation are the most frequently reported adverse events
background: Background Overactive bladder (OAB)/ storage lower urinary tract symptoms ( LUTS ) have a high prevalence affecting up to 90 % of men over 80 years .
  The role of sufficient therapies appears crucial .
  In the present review , we analyzed the mechanism of action of tolterodine extended-release ( ER ) with the aim to clarify its efficacy and safety profile , as compared to other active treatments of OAB/storage LUTS .
  Antimuscarinic drugs are the mainstay of pharmacological therapy for OAB / storage LUTS ; several studies have demonstrated that tolterodine ER is an effective and well tolerated formulation of this class of treatment .