Comparative assessment of efficacy and safety of approved oral therapies for overactive bladder: a systematic review and network meta-analysis.

bladder based on a systematic review and network meta-analysis approach. METHODS: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. RESULT: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. CONCLUSION: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Risk of delirium associated with antimuscarinics in older adults: A case-time-control study.

BACKGROUND: Older adults are at an increased risk of delirium because of age, polypharmacy, multiple comorbidities and acute illness. Antimuscarinics are the backbone of the pharmacological management of overactive bladder. However, the safety profiles of antimuscarinics vary because of their dissimilarities to muscarinic receptor-subtype affinities and are associated with differential central anticholinergic adverse effects. OBJECTIVE: This study aimed to examine delirium risk in new users of oxybutynin and solifenacin in older adults (≥ 65 years). In the secondary analyses, we examined the risk of delirium by type and dose of antimuscarinic. METHOD: We applied a case-time-control design to investigate delirium risk in older adults who started taking oxybutynin and solifenacin. We used a nationwide inpatient hospital data (2005-2016), National Minimum Data Set, maintained by the Ministry of Health, New Zealand (NZ), to identify older adults with a new-onset diagnosis of delirium. Eligible patients were older adults aged 65 at entry into the cohort on 1/1/2006. We used dispensing claims data to determine antimuscarinic treatment exposure. The antimuscarinic included in the study were new users of oxybutynin and solifenacin. These two antimuscarinics are subsidised by the Pharmaceutical Management Agency and are the most frequently used antimuscarinic in NZ. A conditional logistic regression model was used to compute matched odds ratios (MORs) and 95% confidence intervals (CIs). In the case-time-control design, we made separate analyses to evaluate the dose-response risk of delirium. RESULTS: We identified 4818 individuals (mean age 82.14) from 2005 to 2015 with incident delirium and were exposed to at least one of the antimuscarinic of interest. The case-time-control matched odds ratio (MOR) for delirium with oxybutynin was (2.06, 95% confidence interval [CI] 1.07-3.96). Solifenacin was not associated with delirium (0.89 95%CI 0.64-1.23). In the sensitivity analyses, the case-time-control MOR for delirium using a shorter risk period (0-3 days) did not change the results. The dose-response risk of delirium was significant for oxybutynin (0.05, 95%CI 0.02-0.08) but not for solifenacin (-0.01, 95%CI -0.03 to 0.00). In addition, in the subgroup analyses, a statistically significant association of delirium was found for oxybutynin but not for solifenacin in the non-dementia cohort (2.11,95% CI 1.08-4.13) and the dementia cohort (1.25, 95%CI 0.05-26.9). CONCLUSION: The study found that oxybutynin but not solifenacin is associated with a risk of new-onset delirium in older adults. The higher blockade of M1 and M2 receptors by oxybutynin is likely to contribute to delirium than solifenacin, which is highly selective for the M3 receptor subtype. Therefore, the treatment choice with an M3 selective agent must be given due consideration, particularly in those with pre-existing cognitive impairment.

Solifenacin-induced acute urticaria and angioedema: a rare adverse effect.

Antimuscarinics are first-line medication for management of overactive bladder with solifenacin being commonly prescribed. Angioedema is the swelling of mucosa and submucosal tissue. There are no published case reports of drug-induced angioedema involving solifenacin. We report a case of a 41-year-old man with spinal cord injury who presented with oedema of face, lips, tongue and associated pruritic urticaria after taking 5 mg of solifenacin. All other possible causes including food allergy, insect bite, hereditary angioedema, use of NSAIDs, ACE inhibitors and antibiotics were ruled out. The temporal association between solifenacin and angioedema and complete resolution of symptoms after discontinuing the drug suggest that solifenacin was the most probable cause of angioedema in our patient.

Therapeutic efficacy and cognitive adverse events of overactive bladder medication in patients with central nervous system Disorders-A cohort study.

PURPOSE: This cohort study evaluates therapeutic efficacy and adverse events (AEs) of various overactive bladder (OAB) medications for patients with central nervous system (CNS) disorders. METHODS: Patients with OAB and CNS disorders were prospectively enrolled. They were randomly allocated to 3 different treatment subgroups: (1) mirabegron 50 mg once daily (2) solifenacin 5 mg per day, and (3) combined solifenacin 5 mg and mirabegron 50 mg once daily. Efficacy and safety questionnaires and objective parameters were compared among the subgroups, and subgroups between baseline and 3 and 6 months after treatment. AEs, including cognitive dysfunction, were assessed using the Mini-Mental State Examination (MMSE). RESULTS: 102 patients (mean age, 71.8 ± 8.7 years) were enrolled, including 35, 36, and 31 patients received mirabegron monotherapy, solifenacin monotherapy, and combination therapy, respectively. OAB symptoms scores all significantly improved 3 months after treatment in different subgroup. However, PVR increased and VE decreased significantly after treatment in patients receiving solifenacin monotherapy and combination therapy. Dry mouth and constipation were the most common AEs, especially in the solifenacin and combination subgroups. Mild incidence of AEs was noted in patients receiving mirabegron monotherapy. No significant change in MMSE was noted among the subgroups after treatment. CONCLUSION: OAB medication had good therapeutic efficacy in patients who had OAB with CNS disorders, especially in cerebrovascular accident and parkinsonism. No OAB medication or their combination affected cognitive function, whereas minimal AEs were noted with mirabegron. Mirabegron could be recommended as the first choice for managing OAB in these patients.

A systematic review of neurocognitive dysfunction with overactive bladder medications.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to report cognitive dysfunction with commonly used antimuscarinic overactive bladder medications in patients suffering from overactive bladder disorder with and without baseline neurologic conditions. METHODS: We conducted an Ovid MEDLINE, Embase, and PsycINFO search from January 1998 to December 2018 using PRISMA guidelines. Eighteen studies met the inclusion criteria, including 5 randomized controlled trials and 13 observational studies. RESULTS: Cognitive decline was reported with oxybutynin use (5 of 8 studies) and tolterodine use (4 of 7 studies) among patients with and without baseline cognitive impairment. Oxybutynin use was linked to functional, mental, and behavioral decline among patients with Alzheimer's disease (2 studies). No cognitive decline was detected among patients with and without baseline cognitive impairment taking trospium (6 studies), darifenacin (3 studies), imidafenacin (2 studies), and fesoterodine (1 study). Solifenacin was not associated with cognitive decline (2 studies) but was linked to an increased risk of dementia among patients with diabetes (1 study). CONCLUSION: In this review, cognitive decline was reported with oxybutynin and tolterodine use and should be used with caution in adults over 65 years of age. Solifenacin, fesoterodine, and imidafenacin showed mixed results related to central nervous system effect. Trospium and darifenacin were not associated with cognitive decline among patients with and without baseline cognitive impairment.

Mirabegron versus Solifenacin in Children with Overactive Bladder: Prospective Randomized Single-Blind Controlled Trial.

PURPOSE: The purpose of this study is to investigate the efficacy and safety of mirabegron versus solifenacin in the treatment of newly diagnosed overactive bladder (OAB) in children. METHODS: We conducted a prospective randomized controlled study on pediatric patients with newly diagnosed OAB. Patients were randomized into 3 groups: mirabegron (50 mg once daily) in group I, solifenacin (5 mg) in group II, and placebo in group III. Before starting our treatment and at the end of the 3 months course, we obtained a 3-day voiding diary. This diary included incontinence episode per day, mean voided volume per micturition, mean number of micturition per day, and post-void residual urine. Moreover, the parents/patients were asked to rate symptom relief, and the adverse events were recorded throughout the study period. RESULTS: A total of 190 patients aged from 5 to 14 years completed this study. At the end of this trial, both groups I and II showed significant improvement versus placebo regarding our efficacy parameters with no significant difference between group I and II. The overall success rate based on assessment of symptom relief was significantly higher in the treated groups (87.5% in I and 90.2% in II) versus placebo (55.8%). Dry mouth was reported in 2.8, 10, and 0% and constipation in 2.8, 11.4, and 1.4% in group I, II, and III, respectively, without statistically significant difference between group I and placebo. However, there was a significant difference between group II and placebo regarding these side effects. CONCLUSION: Both mirabegron and solifenacin have comparable efficacy regarding the control of OAB symptoms in the newly diagnosed children, but mirabegrone seems to have less side effects.

Comparision effects of solifenacin, darifenacin, propiverine on ocular parameters in eyes: A prospective study.

OBJECTIVE: To evaluate the effects of solifenacin, darifenacin, and propiverine on nasal-, subfoveal-, temporal choroidal thicknesses (NCT, SFCT, TCT), intraocular pressure (IOP) and pupil diameter (PD). MATERIALS AND METHODS: Patients with overactive bladder (OAB) diagnosed according to The International Continence Society were administered with solifenacin, darifenacin or propiverine on a daily basis between November 2017 and May 2018. NCT, SFCT, TCT, IOP, and PD of these patients were measured and compared as initial, fourth and twelfth weeks. RESULTS: A total of 165 patients (330 eyes) with OAB were evaluated. Solifenacin (n=140) signifi cantly reduced IOP from 17.30±2.72 mmHg to 16.67±2.56 mmHg (p=0.006) and 16.57±2.41 mmHg (p=0.002), at the fourth and twelfth weeks, respectively. Darifenacin (n=110) signifi cantly reduced NCT from 258.70±23.96 µm to 257.51±22.66 µm (p=0.002) and 255.36±19.69 µm (p=0.038), at the fourth and twelfth weeks, respectively. Propiverine (n=80) signifi cantly increased PD from 4.04±0.48 mm to 4.08±0.44 mm (p=0.009) and 4.09±0.45 mm (p=0.001), at the fourth and twelfth weeks, respectively. CONCLUSION: These findings can help to decide appropriate anticholinergic drug choice in OAB patients. We finally suggest further well-designed randomized prospective studies with a larger population to evaluate the anticholinergic-related complications in eyes.

Meta-analysis of the efficacy and safety of mirabegron and solifenacin monotherapy for overactive bladder.

AIM: We conducted a meta-analysis to evaluate the safety and efficacy of mirabegron (50 mg) and solifenacin (5 mg) monotherapy for overactive bladder (OAB) during a 12-week cycle. METHODS: Randomized controlled trials (RCTs) of mirabegron and solifenacin for OAB were searched systematically by using MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of retrieved studies were also perused. RESULTS: Five RCTs which compared solifenacin with mirabegron were studied. Mirabegron achieved the same effect as solifenacin in treating OAB. The mean number of incontinence episodes per 24 h (P = 0.20), mean number of micturitions per 24 h (P = 0.11), mean number of urgency episodes per 24 h (P = 0.23), and mean volume voided per micturition (P = 0.05) suggested that mirabegron and solifenacin had no significant differences in terms of OAB treatment. With regard to drug-related treatment-emergent adverse events (DR-TEAEs) and dry mouth, mirabegron showed better tolerance than solifenacin. Post-voiding residual volume showed a distinct difference in the two groups. Hypertension and tachycardia did not show a significant difference between the two groups, but the pulse rate did. CONCLUSION: The therapeutic effect of mirabegron is similar to that of solifenacin, and mirabegron does not increase the risk of adverse events (AEs).

Comparisons of Therapeutic Efficacy and Safety of Solifenacin versus Tolterodine in Patients with Overactive Bladder: A Meta-Analysis.

OBJECTIVES: This meta-analysis was to assess solifenacin and tolterodine in patients with overactive bladder. METHODS: We searched PubMed, the Cochrane Library, EMBASE, CNKI, Wanfang, and ClinicalTrials.gov databases for randomized controlled trials (RCTs). The efficacy endpoint was daily micturition frequency, daily urgency episodes, daily incontinence episodes, and micturition volume per voiding. The safety endpoint was the incidence of the rate of major bleeding, intracranial bleeding, and gastrointestinal bleeding. RESULTS: Seven RCTs met the inclusion criteria and 1,318 patients were included. The meta-analysis showed that, compared with tolterodine, solifenacin was associated with similar daily micturition frequency, daily urgency episodes, daily incontinence episode, and micturition volume per voiding at 8 and 12 weeks of follow-up. Moreover, no significant difference was obtained in the incidence of dry mouth between solifenacin and tolterodine at 8 and 12 weeks of follow-up. However, tolterodine decreased the constipation rate at 12 weeks compared with solifenacin. CONCLUSION: Solifenacin and tolterodine yielded similar results on daily micturition frequency, daily urgency episodes, daily incontinence episodes, micturition volume per voiding, and the incidence of dry mouth. However, tolterodine can decrease the constipation rate at 12 weeks compared with solifenacin.

Comparison of Two Different Drugs for Overactive Bladder, Solifenacin and Mirabegron: A Prospective Randomized Crossover Study.

To assess the efficacy and safety of 2 drugs for overactive bladder (OAB), solifenacin and mirabegron. Fortyseven female OAB patients were randomized into 2 groups. Twenty-three patients were initially prescribed solifenacin for 4 weeks, followed by mirabegron for 4 weeks (group S). The other 24 patients were initially prescribed mirabegron for 4 weeks, followed by solifenacin for 4 weeks (group M). Evaluations included clinical determination of the OAB symptom score (OABSS), International Prostate Symptom Score (IPSS), and Visual Analog Scale. The IPSS significantly improved after the administration of solifenacin in both groups. The OABSS significantly improved in both groups after 4 weeks. In group M, the OABSS after eight weeks was significantly improved compared to that after 4 weeks. However, in group S, it was not significantly improved. Twelve patients experienced adverse events during the solifenacin treatment, while 2 patients experienced adverse events during the mirabegron treatment. Both solifenacin and mirabegron led to improved OAB symptoms. Switching from mirabegron to solifenacin significantly improved the OABSS. However, mirabegron led to fewer adverse events than solifenacin. We recommend that mirabegron be prescribed first for OAB patients. If patients are not satisfied with mirabegron, solifenacin should be used.

Long-term safety and efficacy of antimuscarinic add-on therapy in patients with overactive bladder who had a suboptimal response to mirabegron monotherapy: A multicenter, randomized study in Japan (MILAI II study).

OBJECTIVES: To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron. METHODS: 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. RESULTS: 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. CONCLUSIONS: Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin.

INTRODUCTION: Correction of benign prostatic hyperplasia (BPH) with lower urinary tract (LUT) symptoms (LUTS) is treated with drugs of different pharmacological classes having side effects including suppression of sexual function. AIM: To assess the effect of simultaneous intake of dutasteride and solifenacin on the reversibility of severe LUTS and sexual function in men with BPH. METHODS: Patients from group A took dutasteride 0.5 mg/d, those from group В took dutasteride 0.5 mg/d and solifenacin 10 mg/d, and those from group С took dutasteride 0.5 mg/d and solifenacin 20 mg/d. The duration of the observation was 6 months. The sexual function was rated with the International Index of Erectile Function questionnaire and Men's Sexual Health Questionnaire-ejaculatory dysfunction. The functional status of LUT was rated with International Prostate Symptom Score, overactive bladder questionnaire-awareness tool, diary voiding, and uroflowmetry. MAIN OUTCOME MEASURE: The state of sexual function and function of the LUT in men improved. RESULTS: The erectile function in all men, having participated in the study, did not change [group A, 9.8 (1.6)/9.4 (3.8), P ≥ .05; group B, 10.1 (2.1)/10.5 (3.7), P ≥ .05; group C, 9.7 (1.5)/9.5 (2.6), P ≥ .05]. The ejaculator function significantly decreased in all groups. According to International Prostate Symptom Score, obstruction diminished in this group [incomplete emptying, 3.7 (0.7)/1.5 (0.3), P ≤ .05; intermittence, 3.5 (1.0)/3.5 (1.0), P ≤ .05; weak stream, 3.8 (0.6)/1.5 (0.4), P ≤ .05; straining, 3.4 (0.5)/0.7 (0.7), P ≤ .05] as did hyperactivity [urgency, 2.8 (0.7)/0.9 (0.7), P ≤ .05; nocturia, 2.8 (0.6)/1.2 (0.4), P ≤ .05]. All numbers in the manuscript are given in points unless otherwise stated. The values in parentheses are SD (unless otherwise specified). CLINICAL IMPLICATIONS: The information that a high dose of solifenacin administered concomitantly with dutasteride may contribute to increase in sexual satisfaction and preservation of erectile function at the baseline level can be useful and used by sexologists, urologists, and family doctors. STRENGTH & LIMITATIONS: The combination of dutasteride 0.5 mg/d and solifenacin 10 mg/d saves erectile function and improves sexual satisfaction. At the same time, the symptoms of obstruction and hyperactivity disappear or are reduced in most patients. Nevertheless, we did not study late results of the combined therapy. CONCLUSION: Suggested combination does not impact on erectile function but decreases ejaculator function; however, it does not affect a general high rating of sexual function by patients. Thus, overall sexual function in men with BPH and severe LUTS is not impaired by prolonged intake of double dosage of solifenacin combined with dutasteride. The combination of dutasteride and solifenacin is effective and safe to treat BPH and severe LUTS. Kosilov K, Kuzina I, Kuznetsov V, et al. The Risk of Sexual Dysfunction and Effectiveness of Treatment of Benign Prostatic Hyperplasia With Severe Lower Urinary Tract Dysfunction With Combination of Dutasteride and Solifenacin. J Sex Med 2018;15:1579-1590.

Comparative efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents in overactive bladder: A systematic literature review and network meta-analysis.

AIMS: To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB). METHODS: Literature searches of MEDLINE, Embase, and the Cochrane Library were undertaken to identify randomized controlled trials in OAB (2000-2015) for antimuscarinic agents. A network meta-analysis (NMA) was performed to estimate efficacy and tolerability outcomes for solifenacin 5 mg/day relative to other antimuscarinics. RESULTS: The NMA included 53 eligible trials (published, n = 48; unpublished on search date, n = 5). Solifenacin 5 mg/day was significantly more effective than tolterodine 4 mg/day for reducing incontinence and urgency urinary incontinence (UUI) episodes, but significantly less effective than solifenacin 10 mg/day for micturition; no other statistically significant differences were noted for efficacy. Solifenacin 5 mg/day had a statistically significant lower risk of dry mouth compared with darifenacin 15 mg/day, fesoterodine 8 mg/day, oxybutynin extended-release 10 mg/day, oxybutynin immediate-release (IR) 9-15 mg/day, tolterodine IR 4 mg/day, propiverine 20 mg/day, and solifenacin 10 mg/day. There were no significant differences between solifenacin 5 mg/day and other antimuscarinics for risk of blurred vision, or for 11 of 17 active comparators for risk of constipation. CONCLUSIONS: This NMA suggests that the efficacy of solifenacin 5 mg/day is at least similar to other common antimuscarinics across the spectrum of OAB symptoms analyzed, and is more effective than tolterodine 4 mg/day in reducing incontinence and UUI episodes. Solifenacin 5 mg/day has a lower risk of dry mouth compared with several agents.

Efficacy and tolerability of treatment with mirabegron compared with solifenacin in the management of overactive bladder syndrome: A retrospective analysis.

AIM: The aim of this study was to compare the efficacy and tolerability of solifenacin and mirabegron in patients with overactive bladder (OAB) syndrome. METHODS: We carried out a retrospective analysis in 342 women affected by OAB syndrome; 168 were treated with solifenacin 5 mg/daily and 174 with mirabegron 50 mg/daily. A clinical evaluation, 3-day voiding diary, and urodynamic testing was performed. Patients completed the Overactive Bladder Questionnaire - Short Form, the King's Health Questionnaire, and the Patient Global Impression of Improvement questionnaire. The adverse effects were evaluated. The two groups were compared at baseline and at 12 weeks. RESULTS: After 12 weeks, a significant reduction in the mean number/24 h of voids and urgent micturition episodes/24 h was observed in both groups. Detrusor overactivity decreased from 58.3% to 13.1% in the solifenacin group and from 58% to 11% in the mirabegron group. Twenty (12%) and 18 (10.7%) patients taking solifenacin reported constipation and dry mouth, respectively, versus four (2.3%) and five (2.9%) patients taking mirabegron, respectively, but there was no difference between the groups in the change in vital signs. The Overactive Bladder Questionnaire - Short Form and King's Health Questionnaire scores did not demonstrate significant differences and the abandonment rates in the solifenacin and mirabegron groups were 25.5% and 20%, respectively. CONCLUSION: Solifenacin and mirabegron showed the same efficacy in the treatment of OAB but solifenacin had more adverse effects.

Efficacy and safety of combinations of mirabegron and solifenacin compared with monotherapy and placebo in patients with overactive bladder (SYNERGY study).

OBJECTIVE: To evaluate the potential of solifenacin 5 mg combined with mirabegron 25 or 50 mg to deliver superior efficacy compared with monotherapy, with acceptable tolerability, in the general overactive bladder (OAB) population with urinary incontinence (UI). PATIENTS AND METHODS: After a 4-week placebo run-in, patients aged ≥18 years with wet OAB (urgency, urinary frequency and UI) for ≥3 months who recorded on average ≥8 micturitions/24 h, ≥1 urgency episode/24 h, and ≥3 UI episodes over the 7-day micturition diary, were eligible for randomisation to double-blind treatment [2:2:1:1:1:1 ratio, solifenacin 5 mg + mirabegron 25 mg (combined S5 + M25 group); solifenacin 5 mg + mirabegron 50 mg (combined S5 + M50 group); solifenacin 5 mg; mirabegron 25 mg; mirabegron 50 mg; or placebo for 12 weeks], and 2-weeks' single-blind, placebo run-out. Co-primary efficacy variables were change from baseline to end of treatment (EoT) in the mean number of UI episodes/24 h and micturitions/24 h, assessed using a 7-day electronic micturition diary. Secondary efficacy variables included change from baseline to EoT in the mean volume voided/micturition, change from baseline at weeks 4, 8, 12 and EoT in mean number of UI episodes/24 h, micturitions/24 h, urgency episodes/24 h, urgency UI (UUI) episodes/24 h and nocturia episodes/24 h; the percentage of patients (responders) achieving zero UI episodes/24 h at EoT in the last 7 days prior to each visit, micturition frequency normalisation (<8 episodes/24 h) at weeks 4, 8, 12 and EoT; and the number of UUI episodes and nocturia episodes in the 7-day diary. Safety assessments included incidence and frequency of treatment-emergent adverse events (TEAEs), post-void residual (PVR) urine volume, and changes from baseline in laboratory parameters. RESULTS: Whilst the combined S5 + M50 group was superior to solifenacin 5 mg for UI, with a mean (standard error) adjusted difference of -0.20 (0.12) UI episodes/24 h (95% confidence interval -0.44, 0.04, P = 0.033), there was no statistical superiority vs mirabegron 50 mg [-0.23 (0.12) UI episodes/24 h; P = 0.052]. In secondary analyses, all active treatment groups had greater improvements in UI episodes/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.70 episodes/24 h; combined S5 + M50 group: -0.65 episodes/24 h) that were substantially higher than those obtained with monotherapy (range -0.37 episodes/24 h for mirabegron 25 mg to -0.45 episodes/24 h for solifenacin 5 mg). For micturitions/24 h, adjusted change from baseline to EoT was greater in the combined therapy groups vs monotherapies (combined S5 + M50 group, nominal P values 0.006 and <0.001 vs solifenacin 5 mg and mirabegron 50 mg, respectively; combined S5 + M25 group, nominal P values 0.040 and 0.001 vs solifenacin 5 mg and mirabegron 25 mg, respectively). All active treatment groups had greater improvements in the mean numbers of micturitions/24 h vs placebo, with effect sizes for the combined therapy groups (combined S5 + M25 group: -0.85 micturitions/24 h; combined S5 + M50 group: -0.95 micturitions/24 h) higher than with mirabegron monotherapy (25 mg: -0.36; 50 mg: -0.39 micturitions/24 h) and solifenacin 5 mg (-0.56 micturitions/24 h). The combined S5 + M50 group was statistically significantly superior to both monotherapies at EoT for UUI episodes, urgency episodes and nocturia, with effect sizes that appeared to be additive. The combined S5 + M25 group was statistically significantly superior to mirabegron 25 mg for the same variables, except for nocturia. In responder analyses at the EoT, odds ratios in favour of both combined therapies vs monotherapies were shown for the proportion of patients with zero UI episodes and those achieving micturition frequency normalisation. There was a slightly increased frequency of TEAEs in the combined therapy groups vs monotherapies and placebo. Most of the TEAEs were mild or moderate in severity. Events indicative of urinary retention were reported slightly more frequently in the combined therapy groups vs monotherapy and placebo. PVR volume was slightly increased in the combined therapy groups vs solifenacin 5 mg, mirabegron monotherapy, and placebo groups. There were slightly higher frequencies of dry mouth, constipation, and dyspepsia in the combined therapy groups vs monotherapies. There were no concerns regarding electrocardiograms and laboratory data. CONCLUSION: In the largest OAB study to date, combined therapy with solifenacin 5 mg + mirabegron 25 mg and solifenacin 5 mg + mirabegron 50 mg provided consistent improvements in efficacy compared with the respective monotherapies across most of the outcome parameters, with effect sizes generally consistent with an additive effect. Although the combined S5 + M50 group did not achieve a statistically significant effect vs mirabegron 50 mg in the primary analysis of one of the co-primary endpoints (change from baseline in mean number of UI episodes/24 h), it approached statistical significance (P = 0.052), and the nominal P values for the other co-primary endpoint (micturitions/24 h) were <0.05. Most effects of combined therapy vs monotherapy were observable by week 4. The clinical relevance of the improvements seen with combined therapy for several objective OAB outcome measures was also supported by the improvements of combined therapy vs monotherapy in the responder analyses.

Solifenacin is effective and well tolerated in patients with neurogenic detrusor overactivity: Results from the double-blind, randomized, active- and placebo-controlled SONIC urodynamic study.

AIMS: To investigate the effect on urodynamics of 4 weeks treatment with solifenacin succinate in patients with neurogenic detrusor overactivity (NDO) due to multiple sclerosis (MS) or spinal cord injury (SCI). METHODS: SONIC was a prospective, multicenter, double-blind, phase 3b/4 study investigating the efficacy and safety of solifenacin 10 mg in patients with NDO due to MS or SCI. Patients (n = 189) were randomized to placebo or active treatment (solifenacin 5 mg, 10 mg or oxybutynin hydrochloride 15 mg) for 4 weeks, after a 2-week, single-blind, placebo run-in period. The primary endpoint was change in maximum cystometric capacity (MCC) from baseline to end of treatment. The primary analysis compared solifenacin 10 mg versus placebo; all other comparisons were considered secondary. Secondary endpoints included changes in urodynamic parameters, patient-reported outcomes, and safety assessments. RESULTS: In the primary analysis, solifenacin 10 mg significantly improved mean change from baseline MCC versus placebo (P < 0.001) and was associated with improvements in bladder volume at first contraction and at first leak as well as detrusor pressure at first leak. Similar results were obtained for oxybutynin versus placebo. Patient perception of bladder condition significantly improved with solifenacin 10 mg versus placebo (P = 0.041). There was a clear improvement in quality of life (QoL) in the solifenacin arms versus placebo. The overall incidence of adverse events was low. CONCLUSIONS: In patients with NDO due to MS and SCI, 4 weeks of treatment with solifenacin 10 mg improved urodynamic variables and QoL versus placebo and was well tolerated. Neurourol. Urodynam. 36:414-421, 2017. © 2015 Wiley Periodicals, Inc.

Changes in intraocular pressure and tear secretion in patients given 5 mg solifenacin for the treatment of overactive bladder.

INTRODUCTION AND HYPOTHESIS: To investigate the effect of solifenacin succinate on intraocular pressure (IOP) and dry eye in patients with overactive bladder (OAB). METHODS: The study was conducted prospectively between October 2014 and November 2015. A total of 93 female OAB patients with a mean age of 48.59 ± 11.28 years (range 19-75 years) were evaluated. A full ophthalmic examination, including the Schirmer I test and IOP measurements, was conducted. Solifenacin succinate (5 mg/day) was started orally. All procedures were repeated at the 4- and 12-week follow-up, and the effects and side effects were documented. RESULTS: No statistically significant difference was observed in IOP (p = 0.282, p = 0.189) and tear secretion (p = 0.122, p = 0.071) values from the baseline (day 0) to the 12th week in OAB patients using solifenacin succinate. Solifenacin succinate treatment was terminated in 3 patients owing to dry eye in 1 patient, increased IOP in 1 patient, and systemic side effects in 1 patient. Constipation and dry mouth at various rates were the most common systemic side effects observed. CONCLUSIONS: Solifenacin succinate is useful in eliminating OAB symptoms in female patients, but can cause systemic side effects. It had no significant side effects on tear secretion (Schirmer I) and IOP. We concluded that solifenacin succinate could be reliably used in pure OAB patients without comorbidity in terms of dry eye and IOP. We believe that prospective studies with larger series are still needed to reach a definite conclusion.

Cardiovascular safety in refractory incontinent patients with overactive bladder receiving add-on mirabegron therapy to solifenacin (BESIDE).

AIMS/OBJECTIVES: In the BESIDE study, combination therapy (antimuscarinic [solifenacin] and ß3 -adrenoceptor agonist [mirabegron]) improved efficacy over solifenacin monotherapy without exacerbating anticholinergic side effects in overactive bladder (OAB) patients; however, a potential synergistic effect on the cardiovascular (CV) system requires investigation. METHODS: OAB patients remaining incontinent despite daily solifenacin 5 mg during 4-week single-blind run-in, were randomised 1:1:1 to double-blind daily combination (solifenacin 5 mg/mirabegron 25 mg, increasing to 50 mg after week 4), solifenacin 5 or 10 mg for 12 weeks. CV safety assessments included frequency of CV-related treatment-emergent adverse events (TEAEs), change from baseline in vital signs (systolic blood pressure [SBP], diastolic blood pressure [DBP], pulse rate) and electrocardiogram (ECG) parameters. RESULTS: The frequency of hypertension, tachycardia and ECG QT prolongation, respectively, was low and comparable across combination (1.1%, 0.3%, 0.1%), solifenacin 5 mg (0.7%, 0.1%, 0.1%), and solifenacin 10 mg groups (0.8%, 0%, 0.1%). Adjusted mean (SE) change from baseline to end of treatment (EoT) in SBP, DBP, and pulse rate with combination (0.07 mm Hg [0.38], -0.35 mm Hg [0.26], 0.47 bpm [0.28]), solifenacin 5 mg (-0.93 mm Hg [0.38], -0.45 mm Hg [0.26], 0.43 bpm [0.28]) and solifenacin 10 mg (-1.28 mm Hg [0.38], -0.48 mm Hg [0.26], 0.27 bpm [0.28]) was generally comparable, with the exception of a mean treatment difference of ~1 mm Hg in SBP between combination and solifenacin monotherapy; SBP was unchanged with combination and decreased with solifenacin monotherapy. Mean changes from baseline to EoT in ECG parameters were generally similar across treatment groups, except for QT interval corrected using Fridericia's formula, which was higher with solifenacin 10 mg (3.30 mseconds) vs. combination (0.49 mseconds) and solifenacin 5 mg (0.77 mseconds). CONCLUSION: The comparable frequency of CV-related TEAEs, changes in vital signs and ECG parameters indicates no synergistic effect on CV safety outcomes when mirabegron and solifenacin are combined.

Solifenacin in the Elderly: Results of an Observational Study Measuring Efficacy, Tolerability and Cognitive Effects.

INTRODUCTION: The study aimed to evaluate the efficacy and safety of solifenacin in older patients with overactive bladder (OAB). MATERIALS AND METHODS: Observational data on patients aged ≥70 years and the prescribed flexible dose of solifenacin for OAB were collected at 294 offices of German general practitioners. Baseline and week 12 data included type and severity of OAB symptoms, adverse events, quality of life, and change in cognitive function per Mini Mental State Examination (MMSE). RESULTS: Mean age of 774 patients was 78 ± 6 years. A decrease was observed in all OAB symptoms including a reduction of urinary urgency and micturition, each by 4 episodes per 24 h. No change in mean MMSE scores was apparent at week 12. Adverse events and treatment discontinuations were low at 5.8 and 0.5%, respectively. CONCLUSION: Solifenacin was well-tolerated while OAB symptoms declined at week 12. No relevant effect of solifenacin on cognitive function was observed in this elderly population.

Efficacy and Tolerability of Solifenacin 5 mg Fixed Dose in Korean Children with Newly Diagnosed Idiopathic Overactive Bladder: a Multicenter Prospective Study.

We investigated the efficacy and tolerability of solifenacin 5 mg fixed dose in children with newly diagnosed idiopathic overactive bladder (OAB). A total of 34 children (male/female patients = 16/18) aged under 13 years (mean age: 7.2 ± 2.3; range: 5-12) who were newly diagnosed with OAB from January 2012 to September 2014 were prospectively evaluated with open-label protocol. All patients were treated with solifenacin 5 mg fixed dose once daily for at least 4 weeks. The efficacy and tolerability of solifenacin were evaluated 4, 8, and 12 weeks after the initiation of treatment. The mean voiding frequency during daytime was decreased from 9.4 ± 3.0 to 6.5 ± 2.3 times after the 12-week treatment (P < 0.001). The mean total OAB symptom score (OABSS) decreased from 7.7 ± 4.2 to 3.1 ± 3.1 after the 12-week treatment (P < 0.001). The urgency and urgency urinary incontinence (UUI) domains significantly improved from the 12-week treatment, and complete resolution of urgency occurred in 38.9% of patients and the percentage of children with UUI among urgent patients decreased from 79.4% to 57.1%. According to 3-day voiding diaries, the average bladder capacity increased from 90.4 ± 44.4 to 156.2 ± 67.3 mL (P < 0.001). Drug-induced adverse effects (AEs) were reported in 7 patients (20.6%). Our results indicate that solifenacin 5 mg fixed dose is effective against OAB symptoms, and its tolerability is acceptable without significant AEs in children with OAB.