The overactive bladder in children: a potential future indication for tolterodine

Abstract

Objective To determine the safety, efficacy and pharmacokinetics of tolterodine in children with an overactive bladder. Patients and methods Thirty-three children (20 boys and 13 girls, aged 5-10 years) with an overactive bladder and symptoms of urgency, frequency and/or urge incontinence were enrolled in an open, dose-escalation study. Patients were treated with oral tolterodine 0.5 mg (n=11), 1 mg (n=10) or 2 mg (n=12) twice daily for 14 days. The primary safety endpoint was the change in residual urinary volume, as determined by ultrasonography. In addition, voiding diary variables (frequency and incontinence episodes) and pharmacokinetics were evaluated. Other safety endpoints included laboratory variables, electrocardiogram recordings and reported adverse events. Results There were no safety concerns in terms of the change in residual urinary volume for any of the three dosage groups; values were comparable with baseline after 2 weeks of treatment for all three dosages. Adverse events were reported by 20 patients (six on 0.5 mg, five on 1 mg, and nine on 2 mg). Most adverse events were not considered to be drug-related; of the 13 possibly related events, 10 occurred in those taking 2 mg. Headache was the most commonly reported adverse event. No serious adverse events were reported and there were no general safety concerns.There was an improvement in voiding diary variables in all treatment groups after 2 weeks of treatment, although the efficacy was greatest in those taking 1 mg and 2 mg. Pharmacokinetic findings were consistent with dose linearity over the range 0.5-2 mg. Conclusion The results support the use of 1 mg twice daily as the optimal dose of tolterodine for treating children aged 5-10 years with an overactive bladder. Keywords tolterodine, antimuscarinic agents, children, overactive bladder, dose-finding study IntroductionThe symptoms of an overactive bladder are urgency and frequency, with or without urge incontinence, caused by uncontrolled contractions of the detrusor muscle. As uncontrolled detrusor contractions are mediated by muscarinic receptor stimulation, antimuscarinic agents are the most frequently used medications for treating this condition [1]. Historically, antimuscarinic agents like oxybutynin have been effective for treating the overactive bladder but they are poorly tolerated because they are not selective for the bladder [2]. Side-effects on the parotid gland, CNS, gastrointestinal tract and on the eye limit their clinical usefulness [3]. Particularly frequent and troublesome is dry mouth, which has been shown to cause poor compliance and frequent discontinuation of treatment [1,[4][5][6].Tolterodine is a muscarinic receptor antagonist that has been shown to be effective for treating the overactive bladder [7][8][9]. The advantages of tolterodine are numerous and are ascribed to its selectivity for the bladder over other tissues and to its low lipophilicity. Differences between tolterodine and oxybutynin have been reported in several preclinical studies, including pharmacologi...

Long-term use of solifenacin in pediatric patients with overactive bladder: Extension of a prospective open-label study

“…20 Aside from oxybutynin, which is FDA-approved for children, reports on use in children with OAB are provided for tolterodine, trospium and propiverine. [5][6][7][8][9][10][11][12] Hoebeke and colleagues performed a retrospective uncontrolled study in 138 children with therapy resistant non-neurogenic overactive bladder whom they treated with solifenacin for a mean of 23 months. They found solifenacin effective with an overall 85% response rate, a full response in more than 50% and side effects in only 6.5% of their cohort.…”

A review of adherence to drug therapy in patients with overactive bladder

“…Young patients might be more compliant with treatment if a parent supervises medication dosing. Variation in drug metabolism [21], fewer comorbidities and prescribed medicines in young patients might contribute to fewer or better tolerance of side-effects, and better adherence to therapy.…”

Efficacy of tolterodine as a first‐line treatment for non‐neurogenic voiding dysfunction in children

“…For all patients, the mean ( SD ) DVSS was 14.0 (2.67) and 6.68 (3.67) before and after treatment, respectively; the difference was statistically significant ( P < 0.001). The respective mean ( SD , range) DVSS of girls and boys before treatment was 13.8 (2.79, 8-20) and 14.5 (2.44, [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and after treatment was 6.43 (3.79) and 7.50 (3.34). The mean scores for a subgroup of DVSS questions (numbers 1, 2, 6 and 7) related to detrusor hyperactivity were also significantly different before and after treatment, at 7.63 (1.97) and 2.59 (1.04) ( P < 0.001).…”

“…Munding et al [7] reported that tolterodine may be beneficial for reducing wetting episodes in children with voiding dysfunction, with no severe adverse effects. Hjalmas [8] published pharmacokinetic data and reported that the overactive bladder in children may be a potential future indication for tolterodine. Raes et al [10] evaluated the efficacy and tolerability of tolterodine in unselected children with detrusor hyperactivity, and concluded that tolterodine is well tolerated in children and offers an effective treatment which is better than unselective antimuscarinic drugs for adverse effects.…”