Hypothesis / aims of study
Introduction
Lower urinary tract symptoms (LUTS) are prevalent in the paediatric population. If symptoms are not adequately controlled with urotherapy and management of underlying conditions then medication is often required. Anticholinergics are the mainstay of medical therapy though mirabegron is used in selected patients, usually when anticholinergic options have been exhausted. In the United Kingdom, oxybutynin is the first line drug therapy as it is licensed for children from the age of 5 years. However, oxybutynin is a broad spectrum anticholinergic, the downside of which is a broad side effect profile. In our experience a large number of children do not tolerate this medication. Subsequent prescribing is almost entirely off license even though more specific anticholinergics, such as solifenacin, and mirabegron are better tolerated in adults.
AIMS:
To determine reported side effects for anticholinergics and mirabegron in children attending a specialist urology nurse led clinic. To look in depth at the proportion of children who discontinue oxybutynin, as well as the time to and reason for discontinuation.
Study design, materials and methods
Methods
The electronic patient record database at a single tertiary children’s hospital was searched for children aged 5 and over who were seen in the specialist urology nurse service from June 2016 – April 2021. A retrospective review of the records of children who had at least one visit to the urology nurse clinic which included medication review was undertaken. Children with neuropathic bladder were excluded. Data was analysed using χ² test, Fisher’s exact test, and linear regression.
Results
175 children (128 (73%) female) were included in the data analysis (Figure 1). In the entire cohort, the most common symptoms reported were incontinence (158, 90%), urgency (144, 82%) and frequency (89, 51%). During the period of the study 129 children were prescribed oxybutynin, 82 were prescribed tolterodine, 70 were prescribed solifenacin and 33 were prescribed mirabegron; a number of children were prescribed more than one medication on a sequential basis and 8 received combination therapy with solifenacin and mirabegron. One patient was prescribed trospium and was excluded from the review. Table 1 shows the side effects reported. Children prescribed Solifenacin had significantly fewer side effects when compared to Oxybutynin (p=0.018) and Tolterodine (p=0.037). Whilst the side effects reported with mirabegron were comparable to solifenacin, i.e. fewer reported side effects than both oxybutynin and tolterodine, the number was not statistically significant in this patient cohort (p=0.082).
Out of 129 children who were prescribed Oxybutynin, 100 (78%) discontinued the medication. The reasons documented for discontinuation are given in Table 2. Linear regression analysis showed correlation between time to discontinuation of oxybutynin and age, older patients discontinuing the medication more quickly than younger children (p=0.0102).
Interpretation of results
Oxybutynin is prescribed in the majority of patients yet this medication is associated with a high rate of side effects. In this review 71% of patients discontinued the medication, almost 40% due to side effects. The equivalent data for other medications is currently being captured. In our practice, tolterodine is the second line medication since there is a dosing schedule in the British National Formulary for children (BNFc) although it is not licensed for use in children. The rate of reporting side effects was very similar to oxybutynin, despite the increased selectivity of tolterodine for the urinary bladder. In keeping with their more selective nature, both solifenacin and mirabegron were associated with fewer reported side effects.
The time to discontinuation of oxybutynin ranged from 8-35 weeks. The data analysis thus far does not allow interpretation of whether the side effect was present soon after commencing the medication but not reported / tolerated because of a benefit to symptoms or whether the side effect developed after a prolonged period of time. Of note, older children stopped taking the medication more quickly. This is most likely to be due to an increased likelihood that they would recognise and report a side effect. However, the treatment alogorithm followed in our centre limits the age at which solifenacin and mirabegron can be considered, requiring consultant input which is also likely to influence the timing of medication changes . Younger patients are more likely to be offered alternate formulations of oxybutynin (such as modified release tablets or patches) before moving to the next medication in the pathway.