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

• Published in: Journal of pediatric urology Vol. 19; no. 1; pp. 19.e1 - 19.e13
• Main Authors: Raman, Gayathri, Tunnicliffe, David, Lai, Elise, Bennett, Trish, Caldwell, Patrina
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2023
• Subjects: Adolescent; Adverse effects; Child; Cholinergic Antagonists - adverse effects; Constipation; Humans; Muscarinic Antagonists - adverse effects; Overactive bladder syndrome; Safety; Solifenacin; Solifenacin Succinate - adverse effects; Treatment Outcome; Urinary Bladder, Overactive - drug therapy; Xerostomia - chemically induced; Xerostomia - drug therapy; Overactive bladder syndrome; Safety; Adverse effects; Solifenacin; Child; Adolescent
• ISSN: 1477-5131; 1873-4898
• DOI: 10.1016/j.jpurol.2022.09.014

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.Summary TableSummary of evidence and GRADE rating.OutcomesType of study (N)ResultsRisk of biasInconsistencyIndirectnessImprecisionPublication biasOverall GRADE ratingAdverse effects of solifenacinRCT (2)Cohort studies (10)Constipation:RR 3.5, (95%CI 0.9–13.7)Dry mouth:RR 3.1 (95%CI 0.2–53), Dizziness (RR 1.5 95%CI 0.1–16.3) Behavioural difficulties (RR 3.8, 95% CI 0.4–34.4)Constipation6.8%Dry mouth 6.0%Other gastrointestinal side effects 6.2%Some concerns1 RCT had a low risk of bias and the other high.6/10 cohort studies were of good quality and therefore low risk of biasNo concernsOf the common side effects in the RCT, 3 out of 4 had low heterogeneity.No concernsStudies were performed in the population of interest.Some concernsOnly 2 studies in the meta-analysis with wide confidence intervals crossing the nullSome concernsMost studies had a small sample size and some were in abstract form only.Very Low (+)TolerabilityRCT (2)Cohort studies (7)(Single dose studies removed as not applicable to tolerability)Risk of ceasing due to side effects; RR 2.7 (95%CI 0.8–9.1). I2 statistic = 0%, p value = 0.493.5% of patients in the cohort studies ceased solifenacin due to adverse effects.Some concerns1 RCT had a low risk of bias and the other high.6/10 of the cohort studies were of good quality and therefore low risk of biasNo concernsLow heterogeneityNo concernsStudies were performed in the population of interestSome concernsOnly 2 studies in the meta-analysis with a wide confidence intervalSome concernsMost studies had a small sample size and some were in abstract form only.Very Low (+)