mirabegron and Urinary-Retention

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

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

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveβ 3-adrenoceptor agonists (sβ 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sβ 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sβ 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sβ 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sβ 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sβ 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

Topics: Adrenergic beta-3 Receptor Agonists; Drug-Related Side Effects and Adverse Reactions; East Asian People; Female; Humans; Male; Muscarinic Antagonists; Quality of Life; Receptors, Adrenergic; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention

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

To investigate the protective effect of mirabegron on bladder dysfunction in an acute urinary retention rat model.. Thirty-six 16-week Sprague-Dawley rats were assigned to the mirabegron and normal saline (N/S) groups. Each group of eighteen was divided into sub-groups of 6 for 30 min, 2 h, and 24 h. They were administered mirabegron (10 mg/kg) and N/S daily for 4 weeks, respectively. Mirabegron and N/S groups were divided into sub-groups of 6 rats for 30 min, 2 h, and 24 h. The changes in bladder blood flow were measured using laser Doppler (moorVMS-LDF2). Histopathological examination of the bladder and nitric oxide (NO) measurement were performed.. During the urinary retention phase in the mirabegron group, it showed higher and rapider recovery of blood flow; the lowest at 19.5% ± 3.68% at 3 min, a significant recovery from the lowest value as 23.7 ± 3.4% at 10 min, than that in the N/S group; 15.1 ± 1.84% at 5 min, 23.7 ± 3.4% at 20 min, respectively (P < 0.05). At 30 min, 120 min, and 24 h after reperfusion, the recovery of blood flow in the mirabegron group was significantly higher than that in the N/S group (mirabegron: 41.1 ± 1.7%, 59.9 ± 7.2%, and 89.7 ± 4.4%, N/S: 31.3 ± 2.1%, 47.3 ± 4.5%, 83.9 ± 3.6%, respectively (P < 0.05)). NO levels tended to be higher in the mirabegron group; however, the difference was not statistically significant. Histological examination revealed that the mirabegron group showed recovery close to normal tissue after 24 h.. In an acute urinary retention rat model, mirabegron maintained and restored higher bladder blood flow, resulting in protective and recovery effect after acute urinary retention.

Topics: Acetanilides; Acute Disease; Adrenergic beta-3 Receptor Agonists; Animals; Disease Models, Animal; Rats; Rats, Sprague-Dawley; Thiazoles; Urinary Retention

To provide real-world data on Japanese patients with overactive bladder (OAB) initiating treatment with the β. Full medical histories, including prior/concomitant drug use, were collected before initiating mirabegron treatment. After 12 weeks mirabegron, physicians assessed ADR incidence and treatment effectiveness. Residual urine volume was assessed and patients completed the Overactive Bladder Symptom Score (OABSS) and International Prostate Symptom Score-Quality of Life (I-PSS QoL) surveys at Baseline and 12 weeks. Data were collected between April 2012 and July 2014.. Of 9795 OAB patients (46.8% male; 80.8% ≥65 years), 71.7% had coexisting disease [notably benign prostatic hyperplasia (BPH, 32.4%), hypertension (31.9%), and diabetes mellitus (9.4%)] and 53.4% reported concomitant drug use (27.8% α. In the clinical setting, mirabegron is well tolerated, with no unanticipated ADRs, and is an effective treatment for Japanese patients with OAB.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Diabetes Complications; Drug Administration Schedule; Female; Humans; Hypertension; Male; Middle Aged; Product Surveillance, Postmarketing; Prostatic Hyperplasia; Quality of Life; Severity of Illness Index; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention; Urological Agents

Topics: Acetanilides; Adult; Aged; Aged, 80 and over; Catheterization; Cohort Studies; Female; Humans; Incidence; Male; Middle Aged; Muscarinic Antagonists; Prostatic Diseases; Randomized Controlled Trials as Topic; Residual Volume; Risk; Solifenacin Succinate; Thiazoles; Treatment Outcome; Urinary Bladder, Overactive; Urinary Retention; Urodynamics; Urological Agents