tolterodine-tartrate and mirabegron

Overactive bladder (OAB) is defined as urinary urgency, usually with urinary frequency and nocturia. . The current treatment for OAB includes conservative management, surgery, and pharmacotherapy. Mirabegron is a new drug acting by the ß3-adrenoceptor agonism. This study aimed to review the cost-effectiveness of mirabegron in the treatment of OAB.. We searched published articles in electronic search databases. Ten studies were included in the qualitative analysis. Various antimuscarinics, including oxybutynin, fesoterodine, tolterodine, darifenacin, and trospium were compared with mirabegron. The results were evaluated and compared according to the quality-adjusted life-years (QALY), cost/year, and incremental cost-effectiveness ratio (ICER). Of the ten studies in only three, mirabegron was not a cost-effective strategy. In seven cases, mirabegron was cost-effective.. The cost-effectiveness of mirabegron was variable in different regions; however, most of the studies show the cost-effectiveness of mirabegron. Our study illustrates that mirabegron's ICER in comparison with its comparators is below the willingness to pay threshold even in the countries with low GDP/Capita. Our proposal for future economic studies for OAB pharmacotherapy is to compare different doses, formulations, and administration forms in a real-world context.

Topics: Acetanilides; Cost-Benefit Analysis; Humans; Muscarinic Antagonists; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

A systematic review and meta-analysis was carried out to evaluate the efficacy and safety of mirabegron 50 mg and 100 mg in the treatment of storage lower urinary tract symptoms/overactive bladder in comparison with a placebo and tolterodine 4 mg. A total of 491 articles were collected and eight randomized studies were identified as eligible for this meta-analysis. Overall, eight trials were included in the meta-analysis evaluating 10 248 patients. Mirabegron at both doses of 50 mg and 100 mg, and and tolterodine 4 mg were significantly associated with the reduction of incontinence episodes per 24 h, reduction of mean number of micturitions per 24 h, increase of voided volume and reduction of urgency episodes per 24 h, compared to a placebo. Both mirabegron 50 mg and mirabegron 100 mg were associated with a significant reduction of nocturia episodes when compared with a placebo. Conversely, tolterodine 4 mg did not prove to be more effective than a placebo in the reduction of nocturia episodes. Furthermore, mirabegron 50 mg showed a slightly, but significantly, better efficacy than tolterodine 4 mg in the improvement of nocturia episodes. Mirabegron 50 mg and mirabegron 100 mg shared the same risk of overall treatment-emergent adverse events rate with the placebo. Otherwise, tolterodine 4 mg was associated with a significantly greater risk than the placebo. However, mirabegron 100 mg showed a slight trend toward an increased risk of hypertension (odds ratio 1.41; P = 0.08) and cardiac arrhythmia (odds ratio 2.18; P = 0.06). Mirabegron is an effective treatment for patients with storage lower urinary tract symptoms/overactive bladder, providing a reduction of incontinence, urgency and frequency; an improvement of voided volume with a slight, but statistically, significant improvement of nocturia; with a good safety profile. These findings should be considered for the treatment planning of patients with storage lower urinary tract symptoms/overactive bladder.

Topics: Acetanilides; Humans; Lower Urinary Tract Symptoms; Nocturia; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron, a β3-adrenoceptor agonist, was approved for overactive bladder (OAB), but worsened hypertension was a potential risk based on its mechanism of action. Besides, head to head comparisons were limited between mirabegron and antimuscarinic agents, the prior first-line pharmacotherapy of OAB. In this regard, we performed a systematic review and meta-analysis to compare their efficacy as well as safety, especially in blood pressure changes.. Literature search was conducted in PubMed, Medline and seven randomized clinical trial (RCT) register databases of WHO, EU, USA, Taiwan, China, Japan and Cochrane. Completed RCTs for OAB with mirabegron and antimuscarinics were identified and the last comprehensive search was run in August 2017. Cochrane risk of bias tool was used to assess the potential bias, and RevMan5 software was performed for meta-analysis.. Seven eligible RCTs (four for mirabegron vs. tolterodine and three for mirabegron vs. solifenacin) were included and demonstrated similar efficacy in micturitions, incontinence, and nocturia between mirabegron and antimuscarinics. In hypertension issue, no statistical differences were showed in risk ratio (RR) of hypertension events, change of blood pressure from baseline and change of blood pressure from placebo for all participants. On the other hand, RR of dry mouth was significantly lower in mirabegron users.. Mirabegron was not inferior effective in improving OAB symptoms compared with antimuscarinic agents. In addition, mirabegron presented lower incidence of dry mouth and not higher risk for hypertension. Therefore, mirabegron has potential to be an alternative therapeutic option for OAB control.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Female; Humans; Hypertension; Male; Muscarinic Antagonists; Randomized Controlled Trials as Topic; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

Overactive bladder (OAB) is a particular challenge to treat in older adults with co-morbid conditions taking multiple medications. Antimuscarinics (e.g., solifenacin, fesoterodine) and β3-adrenergic receptor agonists (mirabegron) are similarly efficacious; however, antimuscarinics may be associated with side effects that result in poor persistence and contribute to anticholinergic burden, particularly in those taking other medications with anticholinergic properties. With a mechanism of action distinct from antimuscarinics, mirabegron has a different tolerability profile and does not contribute to anticholinergic burden. The objective of this review was to compare and contrast the tolerability profiles of antimuscarinics and mirabegron in older patients to inform practice.. Prospective trials or retrospective subgroup analyses of antimuscarinics for the treatment of OAB in older patients were identified through a search of PubMed. Tolerability data and results of subgroup analyses of mirabegron in patients aged ≥65 and ≥75 years from a pooled analysis of three trials each of 12 weeks and a 1 year trial are described.. Anticholinergic adverse events (AEs) including dry mouth and constipation were more frequent with antimuscarinics versus mirabegron. In patients aged ≥65 years, dry mouth occurred with a six-fold higher incidence with tolterodine extended-release (ER) 4 mg than with mirabegron 25 mg or 50 mg over 12 weeks, and a three-fold higher incidence with tolterodine ER than mirabegron 50 mg over 1 year. Mirabegron had a low incidence of central nervous system effects. A systematic review of the cardiovascular safety profile of mirabegron has not identified any clinically significant effects on blood pressure or pulse rate at therapeutic doses amongst patients aged ≥65 years.. Mirabegron has a more favorable tolerability profile than antimuscarinics amongst older patients and may provide an improved benefit-to-risk ratio and therefore be considered as an alternative to antimuscarinics for older patients.

Topics: Acetanilides; Administration, Oral; Adrenergic beta-Antagonists; Aged; Benzhydryl Compounds; Blood Pressure; Clinical Trials as Topic; Constipation; Female; Heart Rate; Humans; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Retrospective Studies; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

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

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

To assess the efficacy of mirabegron in the treatment of erectile dysfunction concomitant with lower urinary tract symptoms in benign prostatic obstruction patients.. In this randomized controlled trial, 55 sexually active lower urinary tract symptoms/benign prostatic obstruction patients with concomitant erectile dysfunction were randomly allocated in two groups: the first received mirabegron 50 mg plus doxazosin 2 mg once daily (mirabegron group) and the second received tolterodine 4 mg plus doxazosin 2 mg (tolterodine group) for 12 weeks. The evaluation was based on the International Index of Erectile Function questionnaire, Erection Hardness Score questionnaire, International Prostate Symptom Score, quality of life, uroflowmetry and post-voiding residual. The therapeutic outcomes were assessed at 4 and 12 weeks compared with the baseline.. Only the mirabegron group achieved significant improvement in sexual functions after 4 and 12 weeks. By using ≥5 points difference from the baseline as a cut-off point of change, there was a significant difference in change of direction of the International Index of Erectile Function-15 total score in favor of the mirabegron group; after 12 weeks, the International Index of Erectile Function-15 total score decreased in 0%, was unchanged in 8.3% and improved in 91.7% in the mirabegron group compared with 8.7%, 65.2% and 26.1%, respectively, in the tolterodine group (P < 0.001). Regarding the urinary characteristics, both groups showed significant improvement in the International Prostate Symptom Score, quality of life, and post-voiding residual after 4 and 12 weeks, with no significant difference among them.. Mirabegron improves urinary characteristics and the associated sexual dysfunction in patients with lower urinary tract symptoms/benign prostatic obstruction.

Topics: Acetanilides; Doxazosin; Erectile Dysfunction; Humans; Lower Urinary Tract Symptoms; Male; Prostatic Hyperplasia; Quality of Life; Thiazoles; Tolterodine Tartrate; Treatment Outcome

This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long-term safety and efficacy of antimuscarinic add-on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms.. MILAI II consisted of a 2-week screening period (patients received mirabegron 50 mg once daily) plus a 52-week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment-emergent adverse events (TEAEs), vital signs, and 12-lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post-baseline values reported.. Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV-related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug-related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post-baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group.. A favorable CV safety profile was observed following long-term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms.

Topics: Acetanilides; Aged; Aged, 80 and over; Benzilates; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

Mirabegron, a β3-adrenoreceptor agonist, is an alternative drug to antimuscarinics for overactive bladder (OAB) symptoms.. To summarise safety and efficacy reporting of mirabegron treatment for OAB symptoms.. Pooled data analysed from 10 phase 2-4, double-blind, 12-wk mirabegron monotherapy studies in adults with OAB who had received one or more doses of study drug.. Mirabegron: 25 and 50mg; antimuscarinics: solifenacin (2.5, 5, and 10mg) and tolterodine extended release (4mg).. Baseline OAB-related characteristics, intrinsic and extrinsic factors, and analyses by age (<65 vs ≥65yr and <75 vs ≥75yr) and sex were assessed. Solifenacin 2.5 and 10mg groups were not included in the efficacy analyses (small patient numbers). Safety was evaluated using the proportion of treatment-emergent adverse events. Efficacy variables were derived from bladder diaries (baseline and week 12).. Baseline hypertension and diabetes were more frequent across treatment groups in the older versus younger age groups and in men versus women. Within sexes, frequencies were similar between treatment groups. Some differences were observed in baseline characteristics, including type of incontinence and medical history between sexes. No previously unreported safety concerns were identified. Improvements in efficacy (mean number of incontinence episodes/24h, micturitions/24h, urgency episodes/24h, volume voided/micturition, and nocturia episodes) versus placebo were observed in all treatment groups. Significant treatment-by-subgroup interactions included change from baseline in the mean number of incontinence episodes/24h by age (<65 vs ≥65yr), nocturia by age (<65 vs ≥65yr and <75 vs ≥75yr), and urgency episodes by previous OAB medication.. Data from this integrated database of 10 mirabegron studies reaffirm the safety and efficacy profiles of mirabegron, solifenacin, and tolterodine in adults of different age groups and sexes.. Overactive bladder is a complex of symptoms including a compelling desire to pass urine that leads to increased frequency, which may lead to a degree of incontinence if you do not reach the toilet in time and may wake you from sleep. We pooled data from 10 different studies of mirabegron in patients with overactive bladder symptoms, and looked at the effect in the total number of patients who received the treatment, as well as in different age groups and between men and women. No new safety concerns were identified, and mirabegron improved the symptoms of overactive bladder.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Databases, Factual; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

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

The impact of mirabegron on clinical outcome and urodynamic parameters may be important for clinical practice. Thus, the aim of this study was to compare the clinical outcomes and urodynamic effects of mirabegron (Betmiga 50 mg) versus tolterodine (Detrusitol ER 4 mg) treatment for women with overactive bladder syndrome (OAB).. Women with OAB were randomized to receive 12 weeks of mirabegron 50 mg, tolterodine extended-release 4 mg or placebo treatment. The clinical outcomes and urodynamic effects were compared between the subgroups.. Thirty-three women completed 12 weeks of mirabegron (n = 12), tolterodine (n = 12) or placebo (n = 9) treatment. A significant increase in the volumes at strong desire to void and a decrease in the daytime frequency episodes were identified in the mirabegron and tolterodine groups (all P < 0.05). Nonetheless, a decrease in the total voided volume was identified following mirabegron treatment but not tolterodine (P = 0.02).. Mirabegron and tolterodine exhibit similar changes in the urodynamics and bladder diary parameters. However, mirabegron may decrease the total voided volume. These findings may serve as an initial guide or assist in consultations regarding the treatment of OAB patients with mirabegron.

Topics: Acetanilides; Adult; Female; Humans; Middle Aged; Prospective Studies; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urination; Urine; Urodynamics; Urological Agents

The objective of this study was to assess the tolerability and treatment preference in patients with overactive bladder (OAB) treated with mirabegron or tolterodine.. This was a two-period, 8-week crossover, double-blind, phase IV study (PREFER; NCT02138747) in treatment-naive adults with OAB for 3 months or longer randomized to one of four treatment sequences in a 5:5:1:1 ratio (mirabegron/tolterodine, tolterodine/mirabegron, mirabegron/mirabegron, or tolterodine/tolterodine), separated by a washout period of 2 weeks. The primary endpoint was drug tolerability using the Medication Tolerability scale of the OAB Treatment Satisfaction (OAB-S) questionnaire at end of treatment (EoT). Period-by-treatment interactions were analyzed to determine any effect of drug order. Patient preference, change from baseline in OAB symptoms, and treatment-emergent adverse events (TEAEs) were assessed.. A total of 358 randomized patients completed the OAB-S Medication Tolerability scale questionnaire at one or more visits after the baseline evaluation. The mean (95% CI) OAB-S Medication Tolerability scores were significantly higher (better tolerability) for mirabegron (86.29 [83.50, 89.08]) than for tolterodine (83.40 [80.59, 86.20]; p = 0.004). The period-by-treatment interaction was not significant (p = 0.955). Improvements in OAB-S Medication Tolerability scores at EoT were more evident in women, patients aged ≥65 years, and in patients without baseline incontinence, and were greater with mirabegron than with tolterodine extended release. There were no significant differences in patient preference or improvements in OAB symptoms. Significant differences in favor of mirabegron were observed for anticholinergic TEAEs (20.4% vs. 27.4%; p = 0.042) and specifically for gastrointestinal disorders (14.7% vs. 22.5%; p = 0.015).. Tolerability of mirabegron was significantly higher than that of tolterodine, and patient preference and improvements in OAB symptoms were comparable. Both treatments were well tolerated; however, anticholinergic side effects were higher with tolterodine.

Topics: Acetanilides; Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Preference; Prospective Studies; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

The PREFER study was an assessment of medication tolerability, treatment preference and symptom improvement during treatment with mirabegron (M) and tolterodine (T) extended release (ER) in patients with overactive bladder (OAB). In this analysis of PREFER, patient-reported outcomes (PROs) were assessed during treatment.. PREFER was a two-period, 8-week crossover, double-blind, phase IV study (NCT02138747) of treatment-naïve adults with OAB ≥3 months randomized to 1 of 4 treatment sequences (M/T; T/M; M/M; T/T), separated by a 2-week washout. Tolterodine ER was dosed at 4 mg for 8 weeks and mirabegron was dosed at 25 mg for 4 weeks then increased to 50 mg for the next 4 weeks. At each visit, PROs related to treatment satisfaction, quality of life and symptom bother were assessed using the OAB Satisfaction (OAB-S; 3 independent scales/5 single-item overall assessments), OAB-q (total health-related QoL [HRQoL] and subscales [Sleep, Social, Coping, Concern] and Symptom Bother scale) and Patient Perception of Bladder Condition (PPBC) questionnaires. Responder rates were reported for OAB-q subscales based on a minimal important difference (MID; ≥ 10-point improvement) and OAB-S Medication Tolerability score ≥ 90.. In total, 358 randomized patients received ≥1 dose of double-blind study medication and completed ≥1 post-baseline value (OAB-S scale, OAB-q, PPBC): M/T (n = 154), T/M (n = 144), M/M (n = 30) or T/T (n = 30). At end of treatment (EoT), mirabegron and tolterodine ER were associated with similar mean improvements in 7 of the 8 OAB-S scores investigated, OAB-q scales and PPBC. A higher percentage of patients achieved clinically relevant improvements (MID) in OAB-q scales and OAB-S Medication Tolerability score during treatment with mirabegron than tolterodine ER.. On average, patients with OAB experienced improvements in treatment satisfaction, HRQoL and symptom bother that were of a similar magnitude during treatment with mirabegron or tolterodine ER. However, during mirabegron treatment, patients were more likely to achieve clinically relevant improvements in tolerability and HRQoL (as measured by the MID for the OAB-q or an OAB-S Medication Tolerability score ≥ 90) than during tolterodine ER treatment.. NCT02138747 ; registered May 13, 2014.

Topics: Acetanilides; Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Patient Reported Outcome Measures; Patient Satisfaction; Prospective Studies; Quality of Life; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

To assess patient-reported outcomes (PROs) in patients with overactive bladder (OAB) receiving the novel β. Data from a randomised, double-blind, controlled phase III trial in 1,987 patients aged ≥18 years with OAB symptoms for ≥3 months were analysed. Patients received placebo, mirabegron 50 or 100 mg/day, or tolterodine extended release (ER) 4 mg orally once daily for 12 weeks after a 2-week placebo run-in. Prespecified analysis of PROs (changes in OAB Questionnaire [OAB-q], Patient Perception of Bladder Condition [PPBC], and Work Productivity and Activity Impairment: Specific Health Problem [WPAI-SHP] instrument) in patients treated with mirabegron 50 mg/day, tolterodine ER 4 mg/day or placebo is reported. Post-hoc analyses of OAB-q, PPBC and the Treatment Satisfaction-Visual Analogue Scale (TS-VAS) in patients who were incontinent at baseline are also reported.. Significant improvements over placebo in OAB-q coping and concern from baseline to final visit were observed with mirabegron 50 mg/day. No significant improvements in these parameters were observed with tolterodine ER 4 mg/day. Mirabegron 50 mg/day significantly increased the proportion of patients showing a PPBC improvement over placebo. Mirabegron 50 mg/day also produced greater improvements in WPAI-SHP presenteeism and greater reductions in absenteeism and overall work impairment than placebo or tolterodine ER 4 mg/day. The impact of mirabegron 50 mg/day treatment on PROs in the incontinent population appears to be greater than that in the overall OAB population.. At the approved dose of 50 mg/day, mirabegron significantly improves OAB patients' perception of disease and quality of life, independent of whether they are incontinent at baseline. Neurourol. Urodynam. 35:987-994, 2016. © 2015 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

Topics: Absenteeism; Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Double-Blind Method; Female; Humans; Incontinence Pads; Male; Middle Aged; Muscarinic Antagonists; Patient Reported Outcome Measures; Quality of Life; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To assess the efficacy and safety of mirabegron 50 mg once daily compared with placebo and the active control, tolterodine extended-release (ER) 4 mg once daily, in patients with symptoms of overactive bladder (OAB) in Taiwan, Korea, China, and India.. A 12-week multinational, randomized, double-blind, parallel-group placebo- and active-controlled trial. The primary efficacy endpoint was change from baseline to final visit in mean number of micturitions/24 hr. Secondary endpoints were: mean number of urgency episodes, incontinence episodes and urge incontinence episodes/24 hr, mean number of nocturia episodes per night, mean volume voided per micturition, and quality-of-life (QoL) scores as assessed by the King's Health Questionnaire (KHQ).. Of 1,126 patients who were randomized to receive double-blind study drug, 921 patients (300, 311, and 310 in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively) completed the treatment period. Demographic characteristics were similar across treatment groups. A statistically significant improvement versus placebo in mean number of micturitions/24 hr was seen with mirabegron 50 mg at all timepoints (P < 0.05) as well as final visit (-0.57 with 95% confidence intervals [CIs] of [-1.04, -0.09], P = 0.019). There was no significant difference between treatment groups in improvement from baseline to final visit in any of the secondary outcome measures except volume voided per micturition. The overall incidence of drug-related adverse events was 17.2%, 15.8%, and 21.3%, in the placebo, mirabegron 50 mg, and tolterodine ER 4 mg groups, respectively.. Mirabegron 50 mg once daily for 12 weeks was superior to placebo in reducing the frequency of micturitions in patients with symptoms of OAB in Taiwan, Korea, China, and India.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Asia; Double-Blind Method; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Quality of Life; Recovery of Function; Surveys and Questionnaires; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder; Urinary Bladder, Overactive; Urination; Urodynamics; Urological Agents

Overactive bladder (OAB) is highly prevalent and is associated with considerable morbidity and reduced health-related quality of life. β3-adrenergic receptor (β3-AR) stimulation is a novel alternative to antimuscarinic therapy for OAB.. The objective of this analysis was to assess the cost effectiveness of the β3-AR agonist mirabegron relative to tolterodine extended release (ER) in patients with OAB from a UK National Health Service (NHS) perspective.. A Markov model was developed to simulate the management, course of disease, and effect of complications in OAB patients over a period of 5 years. Transition probabilities for symptom severity levels and probabilities of adverse events were estimated from the results of the randomised, double-blind SCORPIO trial in 1,987 patients with OAB. Other model inputs were derived from the literature and on assumptions based on clinical experience.. Total 5-year costs per patient were £1,645.62 for mirabegron 50 mg/day and £1,607.75 for tolterodine ER 4 mg/day. Mirabegron was associated with a gain of 0.009 quality-adjusted life-years (QALYs) with an additional cost of £37.88. The resulting incremental cost-effectiveness ratio (ICER) was £4,386/QALY gained. In deterministic sensitivity analyses in the general OAB population and several subgroups, ICERs remained below the generally accepted willingness-to-pay (WTP) threshold of £20,000/QALY gained. The probability of mirabegron 50 mg being cost effective relative to tolterodine ER 4 mg was 89.4 % at the same WTP threshold.. Mirabegron 50 mg/day is likely to be cost effective compared with tolterodine ER 4 mg/day for adult patients with OAB from a UK NHS perspective.

Topics: Acetanilides; Adult; Benzhydryl Compounds; Cost-Benefit Analysis; Cresols; Double-Blind Method; Humans; Phenylpropanolamine; Quality of Life; Thiazoles; Tolterodine Tartrate; United Kingdom; Urinary Bladder, Overactive; Urological Agents

To evaluate the efficacy and safety of the β3-adrenoceptor agonist mirabegron, in a Japanese population with overactive bladder (OAB).. This randomised, double-blind, placebo-controlled phase III study enrolled adult patients experiencing OAB symptoms for ≥24 weeks. Patients with ≥ 8 micturitions/24 h and ≥1 urgency episode/24 h or ≥1 urgency incontinence episode/24 h were randomised to once-daily placebo, mirabegron 50 mg or tolterodine 4 mg (as an active comparator, without testing for non-inferiority of efficacy and safety) for 12 weeks. The primary endpoint was the change in the mean number of micturitions/24 h from baseline to final assessment. Secondary endpoints included micturition variables related to urgency and/or incontinence and quality-of-life domain scores on the King's Health Questionnaire. Safety assessments included adverse events (AEs), post-void residual urine volume, laboratory variables, vital signs and 12-lead electrocardiogram.. A total of 1139 patients were randomised to receive placebo (n = 381), mirabegron 50 mg (n = 380) or tolterodine 4 mg (n = 378). Demographic and baseline characteristics were similar among the treatment groups. At final assessment, mirabegron was significantly superior to placebo in terms of mean [sd] change from baseline in number of micturitions/24 h (-1.67 [2.212] vs -0.86 [2.354]; P < 0.001) and mean [sd] change from baseline in number of urgency episodes/24 h (-1.85 [2.555] vs -1.37 [3.191]; P = 0.025), incontinence episodes/24 h (-1.12 [1.475] vs -0.66 [1.861]; P = 0.003), urgency incontinence episodes/24 h (-1.01 [1.338] vs -0.60 [1.745]; P = 0.008), and volume voided/micturition (24.300 [35.4767] vs 9.715 [29.0864] mL; P < 0.001). The incidence of AEs in the mirabegron group was similar to that in the placebo group. Most AEs were mild and none were severe.. Mirabegron 50 mg once daily is an effective treatment for OAB symptoms, with a low occurrence of side effects in a Japanese population.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Asian People; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

The aim of the present review article was to summarize the efficacy and tolerability for mirabegron 50 mg over 12 weeks and 1 year versus placebo (SCORPIO) or tolterodine ER 4 mg (SCORPIO and TAURUS). After a 2-week placebo run-in, adults with overactive bladder symptoms for ≥3 months were randomized if, during a 3-day micturition diary period before baseline, they had an average of ≥8 micturitions/24 h and ≥3 urgency episodes. Efficacy end-points were change from baseline to each study visit and final visit in incontinence, micturitions, volume voided/micturition, urgency incontinence, urgency (grades 3 or 4), level of urgency and nocturia. Additional secondary efficacy variables included patient-reported outcomes. Safety variables included changes in treatment-emergent adverse events and vital signs. For SCORPIO, statistically significant improvements from baseline in efficacy variables and patient-reported outcomes were seen with mirabegron versus placebo from week 4, and were maintained over time. For TAURUS, numerical improvements in efficacy were evident from month 1, and were maintained throughout 12 months. Treatment-emergent adverse events incidence was similar between groups, except for dry mouth, which was reported by fourfold (SCORPIO) and threefold (TAURUS) more patients taking tolterodine than mirabegron. Mirabegron 50 mg for 12 weeks was associated with statistically significant improvements in objective measures of efficacy and patient-reported outcomes. At final visit, improvements with mirabegron 50 mg were statistically greater versus placebo. The efficacy profile of mirabegron 50 mg appears to be maintained over 12 months.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Cresols; Double-Blind Method; Drug Administration Schedule; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention; Urinary Tract Infections; Urination; Xerostomia

Mirabegron, a β(3)-adrenoceptor agonist, has been developed for the treatment of overactive bladder (OAB).. To assess the efficacy and tolerability of mirabegron versus placebo.. Multicenter randomised double-blind, parallel-group placebo- and tolterodine-controlled phase 3 trial conducted in 27 countries in Europe and Australia in patients ≥ 18 yr of age with symptoms of OAB for ≥ 3 mo.. After a 2-wk single-blind placebo run-in period, patients were randomised to receive placebo, mirabegron 50mg, mirabegron 100mg, or tolterodine extended release 4 mg orally once daily for 12 wk.. Patients completed a micturition diary and quality-of-life (QoL) assessments. Co-primary efficacy end points were change from baseline to final visit in the mean number of incontinence episodes and micturitions per 24h. The primary comparison was between mirabegron and placebo with a secondary comparison between tolterodine and placebo. Safety parameters included adverse events (AEs), laboratory assessments, vital signs, electrocardiograms, and postvoid residual volume.. A total of 1978 patients were randomised and received the study drug. Mirabegron 50-mg and 100-mg groups demonstrated statistically significant improvements (adjusted mean change from baseline [95% confidence intervals]) at the final visit in the number of incontinence episodes per 24h (-1.57 [-1.79 to -1.35] and -1.46 [-1.68 to -1.23], respectively, vs placebo -1.17 [-1.39 to -0.95]) and number of micturitions per 24h (-1.93 [-2.15 to -1.72] and -1.77 [-1.99 to -1.56], respectively, vs placebo -1.34 [-1.55 to -1.12]; p<0.05 for all comparisons). Statistically significant improvements were also observed in other key efficacy end points and QoL outcomes. The incidence of treatment-emergent AEs was similar across treatment groups. The main limitation of this study was the short (12-wk) duration of treatment.. Mirabegron represents a new class of treatment for OAB with proven efficacy and good tolerability. TRIAL IDENTIFICATION: This study is registered at ClinicalTrials.gov, identifier NCT00689104.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Australia; Benzhydryl Compounds; Cresols; Delayed-Action Preparations; Double-Blind Method; Europe; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Quality of Life; Single-Blind Method; Surveys and Questionnaires; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urination

Despite several antimuscarinic treatment options for overactive bladder (OAB), there is still a need for distinct treatment approaches to manage this condition. Mirabegron, a β(3)-adrenoceptor agonist, has demonstrated efficacy and tolerability for up to 12 wk in phase 3 trials.. To assess the 12-mo safety and efficacy of mirabegron.. Patients ≥ 18 yr of age with OAB symptoms for ≥ 3 mo.. After a 2-wk single-blind placebo run-in, patients with eight or more micturitions per 24h and three or more urgency episodes in a 3-d micturition diary were randomized 1:1:1 to once-daily mirabegron 50mg, mirabegron 100mg, or tolterodine extended release (ER) 4 mg for 12 mo.. Primary variable: incidence and severity of treatment-emergent AEs (TEAEs). Secondary variables: change from baseline at months 1, 3, 6, 9, and 12 in key OAB symptoms.. A total of 812, 820, and 812 patients received mirabegron 50mg, mirabegron 100mg, and tolterodine ER 4 mg, respectively. Baseline demographic and OAB characteristics were similar across groups. TEAEs were reported in 59.7%, 61.3%, and 62.6% of patients, respectively; most were mild or moderate. Serious TEAEs were reported in 5.2%, 6.2%, and 5.4% of patients, respectively. The most common TEAEs were similar across groups. Dry mouth was reported by 2.8%, 2.3%, and 8.6% of patients, respectively. Adjusted mean changes from baseline to final visit in morning systolic blood pressure were 0.2, 0.4, and -0.5mm Hg for mirabegron 50mg, 100mg, and tolterodine ER 4 mg, respectively. Mirabegron and the active control, tolterodine, improved key OAB symptoms from the first measured time point of 4 wk, and efficacy was maintained throughout the 12-mo treatment period. The study was not placebo controlled, which was a limitation.. The safety and tolerability of mirabegron was established over 1 yr, with sustained efficacy observed over this treatment period.. ClinicalTrials.gov identifier: NCT00688688.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Benzhydryl Compounds; Constipation; Cresols; Delayed-Action Preparations; Double-Blind Method; Female; Headache; Humans; Hypertension; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Single-Blind Method; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence, Urge; Urinary Retention; Xerostomia

To assess the prescribing practices for overactive bladder (OAB) pharmacotherapy based on the prescription trend analysis across different specialties of India.. s: IQVIA (Quintiles and IMS Health) secondary sales audit (SSA), as well as a prescription audit for antimuscarinics and beta-3 adrenoceptor agonists (mirabegron) from 2014 to 2021, were analyzed. The data includes SSA data of various antimuscarinics like solifenacin, oxybutynin, tolterodine, darifenacin, trospium and mirabegron change in the prescription trend of antimuscarinics and mirabegron across different specialties; prescribers overlap analysis for solifenacin and mirabegron among Indian urologists were also analyzed.. Urologists prescription rates of OAB drugs were 65% in 2016 and 54% in 2021. The rate of OAB medication prescription by non-urologist was highest from the surgeon (11%), followed by gynecologists (9%) and consultant physicians (8%) in 2021. In addition, among OAB medication prescription rates for antimuscarinics were 100% in 2016 and 58% in 2021 whereas for mirabegron, it was 0% in 2016 and 42% in 2021. Solifenacin was most frequently prescribed anticholinergics, followed by oxybutynin, tolterodine, darifenacin, and trospium. The proportion of prescribers of OAB medication among urologists was 38% in 2016 and 33% in 2021. Exclusive prescribers of solifenacin were 748 in 2018 and 739 in 2021 at the urologist, whereas for mirabegron, it was 961 in 2018 and 934 in 2021. The compound annual growth rate for prescription of the last 6 years (from 2016-2021) for solifenacin and mirabegron was -3% and 8% respectively.. Urology remained a top prescribing specialty for OAB drugs, although prescription share increased at surgeon and consultant physician. OAB medicines prescriptions by urologists are shifting from leading antimuscarinic solifenacin to beta-agonist mirabegron. Data from this study will ultimately lead to the OAB medication preference by the specialist that could lead to more advanced OAB management.

Topics: Acetanilides; Humans; Muscarinic Antagonists; Prescriptions; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urological Agents

The differential risk of incident dementia associated with receiving various overactive bladder (OAB) drugs is unknown.. To estimate the association of antimuscarinic OAB drug (exposure), compared with a β-3 agonist (mirabegron), and incident dementia.. A population-based nested case-control study was conducted in patients treated with OAB medications in Ontario, Canada. A total of 11 392 patients aged ≥66 yr with a new diagnosis of dementia between 2010 and 2017, and 29 881 age- and sex-matched controls without dementia were included in the study.. Receipt of an antimuscarinic OAB drug or receipt of mirabegron, within the previous 6-12 mo.. Cases developed dementia and Alzheimer's disease. Controls were derived from the general population and matched to cases based on important baseline characteristics. Odds ratios (ORs) for incident dementia, adjusted for demographic and health-related characteristics, were determined.. Patients receiving solifenacin (OR 1.24; 95% confidence interval 1.08-1.43) and darifenacin (OR 1.30; 95% CI 1.08-1.56) in the prior 6 mo had increased odds of incident dementia compared with those receiving mirabegron. In the 6 mo to 1 yr prior to diagnosis, receipt of solifenacin (OR 1.34; 95% CI 1.11-1.60), darifenacin (OR 1.49; 95% CI 1.19-1.86), tolterodine (OR 1.21; 95% CI 1.02-1.45), and fesoterodine (OR 1.39; 95% CI 1.14-1.71) was associated with increased odds of incident dementia compared with receipt of mirabegron. No effect was seen with oxybutynin or trospium. Limitations included misclassification of the outcome and residual confounding associated with the use of health administrative databases.. Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron. Oxybutynin and trospium were not associated with dementia, likely due to a protopathic bias. Careful drug selection is warranted when treating patients with OAB.. In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.

Topics: Aged; Canada; Case-Control Studies; Dementia; Humans; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive

Antimuscarinic (AM) and beta-3-agonist (B3A) treatment are the standard first-line pharmacological treatment used to manage overactive bladder (OAB) patients. Aim of our study was to analyze real-life data of adverse events related to AMs and B3A reported on Eudra-Vigilance (EV) Database.. EV database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of AEs for antimuscarinic and beta-3-agonist per category and severity until January 2021.. Overall, 2313 AEs were reported for oxybutinin, 5129 for solifenacin, 2483 for tolterodine, 3523 for fesoterodine, 787 for trospium, 621 for propiverine and 7213 for mirabegron. Urinary retention was higher for fesoterodine (43%) and tolterodine (23%) when compared to solifenacin (10%), mirabegron (11%) and oxybutinin (4%). Cognitive disorder was uncommon for all the analyzed drugs analyzed. Regarding anticolinergic AEs: vision blurred, dry mouth and constipation were higher for AMs when compared to mirabegron. Their prevalence was higher in female patients. Mirabegron presented a higher risk of hypertension (7%) when compared to oxybutinin (2%, P<0.01), solifenacin (2%, P<0.01), tolterodine (2%, P<0.01) and fesoterodine (1%, P<0.01); the rate of hypertension was higher in females (63%) than males (29%) (P<0.01). The risk of acute urinary retention was also significantly higher (15% vs. 10%, P<0.01) in older patients (>85 years).. Real life data is consistent with registry studies regarding the rate of AEs related to antimuscarinic and beta-3-agonist. However some differences were observed. Female patients present higher rates of AEs when compared to male patients. The risk of acute urinary retention was particularly evident in the octogenarians.

Topics: Aged; Aged, 80 and over; Female; Humans; Hypertension; Male; Muscarinic Antagonists; Solifenacin Succinate; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Retention

Transient receptor potential melastatin 8 (TRPM8) channels may contribute to the pathophysiological bladder afferent hyperactivity, thus a TRPM8 antagonist would be a promising therapeutic target for the bladder hypersensitive disorders including urinary urgency in overactive bladder (OAB). We aimed to investigate a pharmacological effect of KPR-5714, a novel selective TRPM8 antagonist, on TRPM8 channels, M

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Calcium Signaling; Cyclic AMP; Disease Models, Animal; Drug Therapy, Combination; Female; HEK293 Cells; Humans; Muscarinic Antagonists; Rats, Sprague-Dawley; Receptors, Adrenergic, beta-3; Thiazoles; Tolterodine Tartrate; TRPM Cation Channels; Urinary Bladder; Urinary Bladder, Overactive; Urodynamics

Today, monotherapy is the most common pharmacological treatment option for patients suffering from overactive bladder (OAB). Recent reports have indicated potential benefits of combination therapy, using a muscarinic antagonist and a β

Topics: Acetanilides; Animals; Cyclophosphamide; Cystitis; Disease Models, Animal; Drug Therapy, Combination; Male; Nitric Oxide; Random Allocation; Rats; Rats, Sprague-Dawley; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Antidepressive Agents; Benzilates; Benzofurans; Brazil; Clinical Decision-Making; Drug Therapy, Combination; Humans; Mandelic Acids; Muscarinic Antagonists; Nortropanes; Pyrrolidines; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Aged; Aged, 80 and over; Benzhydryl Compounds; Benzofurans; Denmark; Female; Humans; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Norway; Practice Patterns, Physicians'; Prospective Studies; Pyrrolidines; Registries; Solifenacin Succinate; Sweden; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

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 establish a new approach to cystometry using telemetry in conscious rats and to use this technique to determine the role of conscious decision making processes with respect to the initiation of voiding in physiological, inflammatory, and painful conditions.. The pressure transducer of a telemetric transmitter was implanted in the dome of the urinary bladder. After a recovery period of at least 1 month, several investigations of urodynamic parameters were performed after diuresis activation by a pulse of furosemide. The model was characterized by tolterodine and mirabegron under physiological conditions and same animals were reused to evaluate the modification of the voiding pattern under bladder inflammation induced by cyclophosphamide.. The quality of traces and measurement of parameters recorded telemetrically were comparable to those with conventional cystometry. Furosemide induced a reproducible transient increase of urine production and a series of voids that persisted for 60 min. Tolterodine reduced the amplitude of micturition contractions although mirabegron was devoid of any effect. Seven hours after injection of CYP, voiding frequency increased significantly and the micturition amplitude contraction was not altered. However, the mean volume voided during individual micturitions and the total voided volume decreased. During a second exposure to furosemide 24H after CYP injection, the micturition pattern returned to control, however, the micturition volume was still lower than in control.. This telemetric model appears to be as accurate as previously described in conscious conventional cystometry, and allows the repeated evaluation of compounds which may modulate the voiding patterns. Neurourol. Urodynam. 36:308-315, 2017. © 2016 The Authors. Neurourology and Urodynamics published by Wiley Periodicals, Inc.

Topics: Acetanilides; Animals; Diuretics; Female; Furosemide; Rats; Rats, Sprague-Dawley; Telemetry; Thiazoles; Tolterodine Tartrate; Urinary Bladder; Urination; Urodynamics; Urological Agents

Mirabegron, the first selective β

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Benzhydryl Compounds; Cresols; Drug Interactions; Female; Healthy Volunteers; Humans; Middle Aged; Postmenopause; Thiazoles; Tolterodine Tartrate; Urological Agents

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Humans; Patient Preference; Randomized Controlled Trials as Topic; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents; Xerostomia

Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB).. Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4 mg was included as an active control in one study: (1) placebo, mirabegron 50 mg and 100 mg, and tolterodine 4 mg ER; (2) placebo, mirabegron 50 mg and 100 mg; (3) placebo, and mirabegron 25 mg and 50 mg. Data were collected at baseline, week 4, 8, and 12.. Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change.. In modified ITT analyses, mirabegron 50 mg was superior to tolterodine 4 mg in changes from baseline utilities after 12 weeks (p < 0.05); similarly, AUC results showed mirabegron 50 mg to be superior to tolterodine (p < 0.05) and placebo (p < 0.05) with the benefit already apparent at 4 weeks (p < 0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms.. Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4 mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.

Topics: Acetanilides; Analysis of Variance; Benzhydryl Compounds; Clinical Trials, Phase III as Topic; Cresols; Data Interpretation, Statistical; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Phenylpropanolamine; Psychometrics; Quality-Adjusted Life Years; Sickness Impact Profile; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Benzhydryl Compounds; Cresols; Female; Humans; Male; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder, Overactive

Mirabegron, a selective β(3)-adrenoceptor agonist, facilitates urine storage function by exerting a relaxing effect on bladder smooth muscle. Here, we investigated the effect of mirabegron on bladder function during the storage phase. We assessed the effect of mirabegron on the resting intravesical pressure in anesthetized rats and also tested antimuscarinics (oxybutynin and tolterodine) under the same experimental conditions. Mirabegron dose-dependently decreased the resting intravesical pressure, while oxybutynin and tolterodine showed no statistically significant effects on resting intravesical pressure. We also investigated the effect of mirabegron on bladder function using cystometry technique in conscious rats with bladder outlet obstruction. While mirabegron dose-dependently decreased the frequency of nonvoiding contractions, considered an index of abnormal response in bladder storage, no significant effects were noted on the amplitude of nonvoiding contractions, micturition pressure, threshold pressure, voided volume, residual volume, or bladder capacity. Neither oxybutynin nor tolterodine affected the frequency of nonvoiding contractions; however, oxybutynin increased residual volume and tended to decrease voided volume in a dose-dependent manner, and tolterodine dose-dependently decreased voided volume. Taken together, these results shed light on the suggestion of mirabegron as a therapeutic agent, compared with antimuscarinics, with its most prominent effect being the facilitation of bladder storage.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Female; Mandelic Acids; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Wistar; Thiazoles; Tolterodine Tartrate; Urinary Bladder; Urinary Bladder Neck Obstruction

Experimental urethral obstruction in rats alters micturition patterns with non-voiding activity (NVA) during filling cystometry, showing similarity to that observed in human detrusor overactivity. Several drug classes with therapeutic potential in overactive bladder in humans have been tested in this model in rats, rabbits or guinea pigs, but no detailed analysis of drug effects on cystometric patterns has been published. The present study uses a rat model of overactivity with partial bladder outflow obstruction (BOO) in combination with the procedures to analyse NVA to study the effects of the anticholinergic drug tolterodine and the novel β(3)-adrenoceptor agonist mirabegron. The current data for the first time show that NVA in rats with BOO is sensitive to both the muscarinergic antagonist tolterodine and the β(3)-adrenoceptor agonist mirabegron, but with clear differences between the two drugs: during progression of bladder filling, tolterodine affected both the amplitude and frequency of NVA whereas mirabegron affected primarily the frequency. In addition, tolterodine dose-dependently reduced voiding contractions, while mirabegron did not. A model is proposed to account for these observations where both agents act on a 'pacemaker-like' mechanism which is sensitive to cholinergic excitatory and beta-adrenergic inhibitory inputs. Such concepts could provide insights into the nature of overactive bladder and the site of action of key therapeutic drugs.. To investigate the hypothesis that tolterodine and the β(3)-adrenoceptor agonist mirabegron exert their actions on the motor component of the motor/sensory system in the bladder wall: non-voiding activity (NVA).. The present study used standard cystometric techniques and a conscious rat model of partial bladder outflow obstruction (BOO). A single dose of either tolterodine (0.01, 0.1 0.3 or 1.0 mg/kg) or mirabegron (0.03, 0.1, 0.3, 1.0 or 3.0 mg/kg) was given i.v. to each animal.. In the dose ranges used, tolterodine reduced the voiding contraction amplitude, whereas mirabegron did not. Non-voiding activity consisted of small (<0.6 mmHg) and large (>0.6 mmHg) transients. As a fill progressed, both tolterodine and mirabegron reduced the cumulative activity of the large non-voiding contractions, but had little effect on the small transients. Tolterodine affected both the amplitude and frequency of NVA, whereas mirabegron affected primarily the frequency.. Non-voiding activity is sensitive to muscarinergic antagonists and β(3)-adrenoceptor agonists, but there are clear differences between the two drugs. A model is proposed to account for these observations where both agents act on a 'pacemaker-like' mechanism with cholinergic excitatory and adrenergic inhibitory inputs. Such concepts may provide insights into the nature of overactive bladder and the site of action of key therapeutic drugs.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Dose-Response Relationship, Drug; Female; Infusions, Intravenous; Muscarinic Antagonists; Phenylpropanolamine; Rats; Rats, Sprague-Dawley; Thiazoles; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urinary Bladder, Overactive; Urination

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Animals; Benzhydryl Compounds; Cresols; Female; Muscarinic Antagonists; Phenylpropanolamine; Thiazoles; Tolterodine Tartrate; Urinary Bladder Neck Obstruction; Urination