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

Published:September 30, 2022DOI:https://doi.org/10.1016/j.jpurol.2022.09.014

      Summary

      Background

      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.

      Objective

      The aim of this study is to systematically evaluate the safety and tolerability of solifenacin in children and adolescents with OAB.

      Study design

      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.

      Results

      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.

      Discussion

      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.

      Conclusion

      Summary TableSummary of evidence and GRADE rating.
      Outcomes Type of study (N) Results Risk of bias Inconsistency Indirectness Imprecision Publication bias Overall GRADE rating
      Adverse effects of solifenacin RCT (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 concerns

      1 RCT had a low risk of bias and the other high.

      6/10 cohort studies were of good quality and therefore low risk of bias
      No concerns

      Of the common side effects in the RCT, 3 out of 4 had low heterogeneity.
      No concerns

      Studies were performed in the population of interest.
      Some concerns

      Only 2 studies in the meta-analysis with wide confidence intervals crossing the null
      Some concerns

      Most studies had a small sample size and some were in abstract form only.
      Very Low (+)
      Tolerability RCT (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 = 0.49

      3.5% of patients in the cohort studies ceased solifenacin due to adverse effects.
      Some concerns

      1 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 bias
      No concerns

      Low heterogeneity
      No concerns

      Studies were performed in the population of interest
      Some concerns

      Only 2 studies in the meta-analysis with a wide confidence interval
      Some concerns

      Most studies had a small sample size and some were in abstract form only.
      Very Low (+)

      Keywords

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