Tolerability Of Solifenacin Research Articles

Comparative Analysis of Solifenacin Plus Desmopressin Versus Desmopressin Alone in the Treatment of Primary Mono Symptomatic Nocturnal Enuresis

ObjectivesTo compare the efficacy and tolerability of Solifenacin plus Desmopressin and Desmopressin alone in the treatment of primary monosymptomatic nocturnal enuresis (PMNE). MethodsA total of 88 children, 5–14 years old, diagnosed with PMNE were enrolled in this randomized control trial (RCT) from June 2017 to June 2020. After informed written consent patients were randomized to one of the two therapeutic groups. Group 1 received one puff of desmopressin nasal spray 1 h before bedtime every night. Group 2 received one pill of solifenacin 5 mg plus one puff of desmopressin nasal spray 1 h before bedtime every night. All patients were evaluated after three months for their response to treatment and drug side effects. ResultsThe mean age in desmopressin alone group and solifenacin plus desmopressin group was 8.1 ± 2.2 (5–14) and 7.9 ± 2.2 (5–14) years respectively (p-value >0.05). In group 2, 37/44 (84.09%) patients achieved complete response after three months of treatment in comparison to group 1 in which 27/44 (61.36%) patients showed complete response (p-value <0.05). In group 1, 8/44 (18.18%) patients developed treatment related side effects whereas in group 2, 12/44 (27.27%) patients developed side effects (p-value >0.05). No case of discontinuation of treatment due to side effects was observed in any of the two groups. The recurrence rate was also significantly lower in group 2 in comparison to group 1 (8.1% vs 33.3%, p-value <0.05). ConclusionOur study demonstrated that the combination of Solifenacin plus Desmopressin is more effective than desmopressin monotherapy in the treatment of PMNE with an acceptable tolerability profile. Level of EvidenceLevel I.

Safety and tolerability of solifenacin in children and adolescents with overactive bladder- a systematic review

Solifenacin is an anticholinergic that is used to treat overactive bladder syndrome (OAB) in children. It is important to ascertain the safety and tolerability of solifenacin in the paediatric population as solifenacin offers an alternative, is more bladder specific, and should have less anticholinergic side effects than other therapies. The aim of this study is to systematically evaluate the safety and tolerability of solifenacin in children and adolescents with OAB. We included studies that reported the safety and tolerability of solifenacin in children and adolescents. All study types were included. Electronic searches were conducted in Ovid MEDLINE, Ovid Embase, TRIP, CINAHL and ICTRP on the 18th of January 2022. Risk of bias was assessed with the Cochrane Risk of Bias tool 2.0 (ROB-2) for randomised controlled trials (RCTs) and the Newcastle-Ottowa scale for cohort studies. A total of twelve studies including two RCTs were included in this review. Results from the meta-analysis of RCTs showed the commonest side effects were constipation (RR 3.5, 95%CI 0.9-13.7) and dry mouth (RR 3.1 95%CI 0.2-53). In terms of tolerability, the effect estimate of ceasing solifenacin due to an adverse effect was 2.7 (95%CI 0.8-9.1). Within the cohort studies, out of the 779 patients 21.7% experienced side effects. The most common side effects were constipation (6.8%) and dry mouth/lips (6.0%) and 3.5% of patients ceased solifenacin due to adverse effects. Overall, the certainty of the evidence for side effects and tolerability were very low. The reported incidence of side effects is low, and less than reported with oxybutynin use. However, the very low certainty of the evidence means the findings should be interpreted with caution. There is limited reporting of a prolonged QTc interval on ECG. Studies that described this only had an increase of QTc from baseline and not a clinically significant prolonged QTc that resulted in arrhythmias. Solifenacin is an alternative anticholinergic for the treatment of OAB in children. However, given the paucity of good quality data on safety and tolerability it should be used cautiously in children with close monitoring for potential side effects.

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.

To compare efficacy and tolerability of solifenacin 5 mg/day versus other oral antimuscarinic agents for the treatment of overactive bladder (OAB). 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. 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. 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 solifenacin in men with overactive bladder: results of an observational study

To evaluate the efficacy and safety of solifenacin for the treatment of OAB in men. This prospective observational study, reflective of actual practice patterns, was conducted in men older than 18 years who were prescribed solifenacin for the treatment of OAB symptoms. Men with suspected bladder outlet obstruction were excluded. The primary efficacy measure was change in OAB symptoms after 12 weeks of solifenacin. Also assessed were changes in severity of urinary urgency, IPSS, quality of life, cognitive function, and adverse events. Data were analyzed using descriptive methods. A total of 799 men recruited at 251 centers, average age 67 years (range 27-92), received solifenacin 5 mg or 10 mg/day. Mean episodes of urinary urgency, frequency, and nocturia decreased by 4.4, 3.6, and 1.4 episodes/24 h, respectively. As per IPSS, severe urinary symptoms were reported by 20.4 % at baseline versus by 2.3 % at week 12. Both voiding and storage symptoms showed improvement. Patient-reported general health condition was excellent/good for 39 % at baseline increasing to 76 % at week 12. Adverse event rate was 5.5 %, and discontinuation of solifenacin due to an event was 1.6 %. No change in post-void residual urine volume was experienced in 80%, while an increase of ≥50 mL was observed in 2.2 %; no cases of acute urinary retention occurred. Baseline mean MMSE was 27.5 points versus 27.9 points at week 12. Solifenacin reduced all OAB symptoms, was well tolerated, and had no apparent effect on post-void residual urine volume. Cognitive function was unaltered in this population of older men with OAB.

Patient-reported outcome of solifenacin treatment among women experiencing urinary urgency and urgency incontinence

ObjectiveTo evaluate treatment success and tolerability of solifenacin among women with urinary urgency (UU) and urgency urinary incontinence (UUI). MethodsIn a prospective, observational, multicenter pilot study in Slovenia and Croatia, 100 women with UU and UUI were enrolled between January 2011 and July 2011. Patients received 5mg of solifenacin once daily for 12weeks and completed a 3-day bladder diary, urgency questionnaire, Urogenital Distress Inventory (UDI), and Incontinence Impact Questionnaire (IIQ). ResultsOverall, 91 women completed 12weeks of treatment. Severity, frequency, and bother of UU significantly had decreased at weeks 4 and 12 (P<0.001). Improvement in UU led to an improvement in mean IIQ score: a reduction in UU frequency had the greatest impact (P=0.006). The mean treatment success rate was 74.2% (by visual analog score) and was closely related to the mean change in irritative UDI score (r=0.39; P<0.001). Treatment success was greatest for patient perception of intensity of urgency scale (PPIUS; P=0.003), UU bother (P=0.017), and micturition frequency (P<0.026). Dry mouth occurred in 35.2% of women at 4weeks, and 27.7% at week 12. ConclusionSolifenacin treatment was effective and well-tolerated among women with UU and UUI. All overactive bladder symptoms had improved by week 12.

Therapie der überaktiven Blase

Epidemiological data demonstrate an increasing prevalence of symptoms of overactive bladder (OAB) with age not only in women, but especially in men. Despite a comparable prevalence, however, men are still highly underrepresented in most large randomized studies on the effect of antimuscarinic drugs. In this subgroup analysis of the CAP Study the efficacy and tolerability of solifenacin was examined in 111 men with symptoms of OAB. The study was performed in a network between general practitioners and urologists under routine conditions over a period of 12 months. Treatment with solifenacin reduced all symptoms of OAB significantly, and the use of pads decreased by more than half. The tolerability of therapy was judged as "excellent" or "good" by over 95% of doctors and patients. This subgroup analysis of the CAP Study confirms the good efficacy and tolerability of solifenacin in male OAB in daily practice over a treatment period of 1year.

Efficacy and Tolerability of Solifenacin in Patients Aged ⩾ 65 Years with Overactive Bladder: Post-Hoc Analysis of 2 Open-Label Studies

Background: Antimuscarinics have proven efficacy as first-line therapy in overactive bladder (OAB); however, data on their use in older adults are needed. Objective: To assess the efficacy and tolerability of solifenacin in patients aged ≥ 65 years, we conducted post-hoc analyses of data from VESIcare® Open-Label Trial (VOLT) and VESIcare® Efficacy and Research Study US (VERSUS). Methods: In both of these 12-week, open-label, flexible-dosing studies involving 2645 patients with OAB for ≥ 3 months, patients received 5 mg solifenacin daily for 4 weeks, with an option to increase to 10 mg at week 4 (both studies) and week 8 (VOLT). VERSUS patients had received tolterodine extended release 4 mg for ≥ 4 weeks without sufficient subjective improvement in urgency (mean ≥ 3 urgency episodes/24 h). Baseline values 14 days after tolterodine washout were used for comparison with VOLT. Common study endpoints were the Patient Perception of Bladder Condition (PPBC) scale and the Overactive Bladder Questionnaire (OAB-q). VOLT used a horizontal visual analog scale (VAS), and diary-recorded symptom data were captured in VERSUS. Results: In the full analysis sets (FAS), 40% of VOLT and 44% of VERSUS patients were aged ≥ 65 years. After 12 weeks of solifenacin, older patients experienced decreases in OAB symptoms, and improvements from baseline on the PPBC, OAB-q, and VAS. In total, 59% of older VOLT and 62% of older VERSUS patients reported ≥ 1 treatment-emergent adverse event (AE); the AEs were mostly anticholinergic and of mild-to-moderate severity. Results were consistent with younger patients and the FAS. Conclusions: In this large group of older patients, flexibly dosed solifenacin was associated with reductions in diary-documented OAB symptoms (VERSUS). In both studies, solifenacin was associated with improvements in measures assessing patients' perception of their bladder problems, symptom bother, and aspects of health-related quality of life. Adverse event rates in older patients were comparable to those in younger patients and the FAS.

Tolerability of solifenacin and oxybutynin immediate release in older (>65 years) and younger (≤65 years) patients with overactive bladder: sub-analysis from a Canadian, randomized, double-blind study

Objective:Overactive bladder (OAB) is a common condition whose prevalence increases with age. Antimuscarinic agents are the pharmacologic treatment of choice, but adverse events such as dry mouth may lead to early discontinuation. The purpose of this analysis was to compare the incidence and severity of dry mouth and other adverse events with solifenacin 5 mg/day and oxybutynin immediate release (IR) 15 mg/day in patients ≤65 years and >65 years in the Canadian VECTOR study (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients).Research design and methods:VECTOR was a randomized, multicentre, prospective, double-blind, double-dummy study in 132 subjects with ≥1 urgency episode per 24 h, with or without urgency incontinence, and ≥8 micturitions per 24 h for ≥3 months. After a 2-week washout, patients received solifenacin 5 mg once daily or oxybutynin IR 5 mg tid for 8 weeks. For the current post-hoc analysis, adverse events were evaluated in subgroups of patients ≤65 years and >65 years, using a full logistic regression model, multinomial logit regression model and reduced model.Clinical trial registration:NCT00431041.Results:The incidence and severity of dry mouth and other adverse events with solifenacin were similar between younger and older patients. In both age subgroups, solifenacin 5 mg/day was associated with fewer episodes and lower severity of dry mouth, and a lower discontinuation rate, compared with oxybutynin IR 15 mg/day.Conclusions:Solifenacin 5 mg/day was better tolerated than oxybutynin IR 15 mg/day in younger (≤65 years) and older (>65 years) subgroups. Solifenacin was equally well tolerated in both age subgroups. Limitations of the analysis were that the study was not preplanned to perform post-hoc subgroup analysis, patients knew that dry mouth was a primary outcome, and the study used fixed doses of each drug.

Impact of solifenacin on quality of life, medical care use, work productivity, and health utility in the elderly: An exploratory subgroup analysis

Background: Overactive bladder (OAB) is a common problem among the elderly and a financial burden to society. The prevalence of OAB increases with age and affects ≥25% of people aged ≥65 years. Objective: The goal of this exploratory subgroup analysis of the VESIcare Efficacy and Research Study US (VERSUS) was to assess changes in health-related quality of life (HRQoL), medical care resource utilization, work and activity impairment, and health utility among elderly patients with OAB who continued to have urgency symptoms with tolterodine and were willing to try solifenacin. Methods: This was a 12-week, multicenter, prospective, open-label, noncomparative, flexible-dosing study designed to assess the efficacy and tolerability of solifenacin. Patients who received tolterodine 4 mg/d for ≥4 weeks but continued to experience urgency symptoms (≥3 urgency episodes/24 hours) were enrolled. This exploratory analysis describes results from 2 elderly cohorts (patients 65 to 74 years and ≥75 years of age). After a washout period of ≥14 days, patients began treatment with solifenacin 5 mg/d with dosing adjustments allowed at week 4 (to 10 mg/d) and at week 8 (back to 5 mg/d for patients whose dose was increased to 10 mg/d at week 4). Outcomes were assessed using the OAB-q (a questionnaire specific to OAB and HRQoL), the Work Productivity and Activity Impairment-Specific Health Problem index, the Medical Care Use Index, and the Health Utilities Index Mark 2 and Mark 3 (HUI2/3), administered at the prewashout and week-12 visits. Results: The subgroup analysis included 108 patients 65 to 74 years of age and 86 patients ≥75 years of age. Patients in both age groups experienced significant improvement in HRQoL ( P < 0.001), as well as significant reductions in nonprotocol-related office visits ( P < 0.001) and activity impairment ( P < 0.025). A significant reduction in the use of pads/diapers was reported for patients 65 to 74 years of age ( P < 0.018), and patients in this age group who were working reported significantly less impairment related to OAB while working during solifenacin treatment than during tolterodine treatment ( P < 0.042). No significant differences in HUI2/3 scores were observed in either of the elderly subgroups. Conclusions: Overall, solifenacin was found to improve symptom bother, HRQoL, work productivity, activity participation, and reduced medical care resource utilization in these elderly subjects with OAB who continued to have urgency symptoms with tolterodine and were willing to try solifenacin. This was an exploratory subgroup analysis of an open-label, noncomparative study; further research is needed to confirm these results.

Cardiovascular Safety and Overall Tolerability of Solifenacin in Routine??Clinical Use

Muscarinic receptor antagonists are the standard of care for patients with overactive bladder (OAB). However, they can increase heart rate, and this can be disadvantageous in patients with coronary heart disease (CHD) or congestive heart failure (CHF). Comedications frequently used in the treatment of cardiovascular disease can further increase the risk for elevation of heart rate. As such high-risk patients have not been well represented in most randomized trials of muscarinic receptor antagonists, we investigated whether the muscarinic receptor antagonist solifenacin alters heart rate or has other cardiovascular adverse effects during routine use in OAB patients. The study evaluated these effects both in the overall group and in pre-defined risk groups. The overall tolerability and safety of solifenacin were also explored. This open-label, post-marketing surveillance study was specifically designed to evaluate the cardiovascular safety of solifenacin 5-10 mg once daily during a 12-week treatment course without specific inclusion or exclusion criteria but with systematic documentation of heart rate-relevant co-morbidities and comedications. The study was conducted in 4450 patients with OAB under the care of office-based urologists. The primary outcome measurement was heart rate. Secondary outcome measures were blood pressure and overall adverse events, which were systematically recorded before, during (after 1 week) and at study end; in many cases, an ECG was also conducted. CHD, previous myocardial infarction or CHF were reported by 11.9%, 1.6% and 7.0% of patients, respectively, and >60% were receiving at least one comedication. An ECG was conducted prior to solifenacin treatment in 915 patients and revealed abnormalities in 17.3%. At study end, 72.4% and 19.1% of patients were taking solifenacin 5 mg and 10 mg, respectively. No clinically relevant alterations in mean heart rate (75.2 +/- 8.2 beats/min pre-treatment vs 74.5 +/- 7.6 beats/min at study end) or mean blood pressure (137/82 mmHg pre-treatment vs 134/81 mmHg at study end) were observed. In the subgroup of patients who underwent ECG both before and during treatment, no increase in the prevalence of pathological findings was noted. Adverse effects were rare (affecting 4.8% of patients), and treatment discontinuations due to adverse effects occurred in only 1.4% of patients. Among various possible cofactors, only age >80 years and the presence of comedications significantly affected adverse event incidence. In real-life conditions, i.e. with inclusion of large numbers of patients with cardiovascular co-morbidities and taking comedications, therapeutically effective doses of solifenacin did not increase heart rate or blood pressure.

Pharmacokinetics, Safety, and Tolerability of Solifenacin in Patients With Renal Insufficiency

To evaluate the pharmacokinetics, safety, and tolerability of solifenacin in patients with mild, moderate, or severe renal disease, eighteen patients with renal disease and six healthy volunteers Received a single oral dose of solifenacin (10 mg). Pharmacokinetic parameters were assessed from blood samples drawn over a 360-h period. Safety and tolerability were also evaluated. Total mean ± S.D. exposure (ng ⋅ h/mL) to solifenacin in healthy individuals (1190 ± 403) was increased in patients with renal disease (mild: 1784 ± 792, moderate: 1559 ± 555, severe: 2530 ± 700), and elimination half-life (mean ± S.D. [h]) was prolonged (healthy: 68.2 ± 27.2, mild: 89.1 ± 34.5, moderate: 90.6 ± 27.3, severe: 111 ± 38.3). A significant correlation was found between creatinine clearance and pharmacokinetic parameters for exposure and apparent oral clearance. No deaths or serious adverse events occurred during the study. Solifenacin 10 mg was well tolerated in patients with renal disease. Solifenacin displays a higher exposure and a prolonged half-life in patients with renal impairment, especially severe. Therefore, while no special cautions are necessary for patients with mild/moderate renal impairment, patients with severe renal impairment should receive no more than 5 mg solifenacin once daily.

Efficacy and tolerability of solifenacin in elderly subjects with overactive bladder syndrome: A pooled analysis

Background: Overactive bladder (OAB) syndrome is characterized by urinary frequency and urgency with or without urge incontinence, and often accompanied by nocturia. The prevalence of OAB increases with aging; it is a particularly common condition among the elderly, affecting at least 25% of people aged ≥65 years. Objective: The goal of this study was to assess the efficacy and tolerability of solifenacin 5 and 10 mg once daily for treating elderly subjects with OAB. Methods: This was a retrospective analysis of pooled data from 4 studies. Data were analyzed from elderly subjects (aged ≥65 years) with OAB who were treated with solifenacin in four 12-week, double-blind, Phase III, international, multicenter, randomized, parallel-group, fixed-dose, placebo-controlled studies and from elderly subjects who received solifenacin in a 40-week, open-label, flexible-dose extension trial that enrolled subjects who completed 2 of the double-blind studies. Micturition data were collected from diaries completed during the 3 days before each study visit. Efficacy end points included mean change from baseline for the number of incontinence episodes/24 hours, urgency episodes/24 hours, number of micturitions/24 hours, and volume voided/micturition. The proportion of subjects who became continent or had no urgency episodes at end point was also evaluated. Results: The mean age of the subjects in the 12-week, double-blind studies (N = 1045; 781 women, 264 men) was 71.9 years; mean age in the 40-week extension trial (N = 509; 359 women, 150 men) was 71.2 years. The majority of subjects (74.7% in the 12-week, double-blind studies and 70.5% in the 40-week extension trial) were female, and >90% of the elderly subjects were white. The duration of OAB ranged from 0 to 66 months, and 43.7% had received previous medical therapy for OAB. The completion rate for elderly subjects was 85.5% for the 12-week, double-blind studies and 80.0% for the 40-week extension trial. Efficacy end points at week 12 of double-blind treatment demonstrated statistically significant improvements in the symptoms of OAB with solifenacin compared with placebo. Mean (SE) changes in number of incontinence episodes/24 hours were −1.5 (0.17) for the 5-mg dose and −1.9 (0.14) for the 10-mg dose compared with −1.0 (0.14) for placebo ( P = 0.013 for the 5-mg dose and P < 0.001 for the 10-mg dose, vs placebo); mean (SE) changes in the number of urgency episodes/24 hours were −3.2 (0.27) for the 5-mg dose and −3.2 (0.19) for the 10-mg dose compared with −1.6 (0.18) for placebo ( P < 0.001 for both doses vs placebo); mean (SE) changes in the number of micturitions/24 hours were −2.0 (0.17) for the 5-mg dose and −2.5 (0.13) for the 10-mg dose compared with −1.1 (0.13) for placebo ( P < 0.001 for both doses vs placebo); mean (SE) changes in the volume voided/micturition were 30.2 (3.24) mL for the 5-mg dose and 46.2 (2.55) mL for the 10-mg dose, compared with 9.1 (2.39) mL for placebo ( P < 0.001 for both doses vs placebo). The proportion of subjects with restoration of continence was 49.1% and 47.3% of the 5- and 10-mg treatment groups, respectively, compared with 28.9% of the placebo group ( P < 0.001 for both doses vs placebo). The proportion of subjects with resolution of urgency was 34.6% and 24.9% for the 5- and 10-mg treatment groups, respectively, compared with 16.9% of the placebo group ( P < 0.001 for the 5-mg dose and P < 0.01 for the 10-mg dose). Improvements in incontinence, urgency, and micturitions were maintained during the 40-week extension trial. The most common adverse events in both the double-blind and extension trials were dry mouth, constipation, and urinary tract infection. Most adverse events were mild to moderate in nature and did not result in treatment discontinuation. Conclusions: In these pooled analyses, solifenacin 5 and 10 mg once daily were efficacious and well tolerated in the treatment of these elderly subjects with OAB. Solifenacin therapy was also associated with a high level of persistence in a 40-week extension trial.