Long-term tolerability of tolterodine extended release in children 5-11 years of age: results from a 12-month, open-label study.
ABSTRACT To evaluate the long-term tolerability of tolterodine extended release (ER) in children (aged 5-11 yr) with urgency urinary incontinence (UUI).
This was a multicenter, open-label extension of a 12-wk, double-blind, placebo-controlled study of tolterodine ER. Patients had UUI suggestive of detrusor overactivity (>/=1 diurnal incontinence episode per 24h for >/=5 of 7 d) and >/=6 voids per 24h at baseline and had completed the 12-wk double-blind study. Patients received tolterodine ER (2mg once daily) for 12 mo. The primary end points were the incidence and severity of adverse events (AEs) and the incidence and reasons for withdrawals. Visits were scheduled at 3, 6, 9, and 12 mo, and investigators were instructed to report all AEs. At 6 and 12 mo, vital signs were recorded and a physical examination was performed.
A total of 318 patients were enrolled (double-blind tolterodine ER, n=221; placebo, n=97). The majority of patients were white (90%), mean+/-SD age was 7.6+/-1.5 yr, and 54% were boys. Forty-nine percent of patients reported >/=1 AE during the study, similar to that observed in the preceding 12-wk study (42%). The most frequent AEs were urinary tract infection (7%), nasopharyngitis (5%), headache (5%), and abdominal pain (4%); 111 (35%) patients withdrew. The most common reasons for withdrawal were lack of efficacy (12%), symptom improvement (8%), and withdrawn consent (6%). Ten patients (3%) withdrew because of AEs.
Long-term treatment with tolterodine ER was well tolerated in children with UUI.
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ABSTRACT: Pharmacological treatment for overactive bladder has centred around the interruption of the detrusor activity that is central to urge and incontinence symptoms. The majority of patients with this disorder are treated with antimuscarinic agents. These drugs have been demonstrated to improve urgency, frequency of micturition and urge incontinence, all of which are primary symptoms of overactive bladder; however, they are also commonly associated with anticholinergic adverse effects, most notably dry mouth. Attempts to increase tolerability have included the development of advanced formulations that regulate release of the active ingredient and the development of pharmacological agents that target the desired bladder receptors more specifically and accurately. Although all agents provide good efficacy, tolerability is greatly affected by the formulation used to deliver the active pharmacological agent, as well as the specificity of the targeted receptors. Clinical trials involving a transdermal formulation of oxybutynin have shown that this delivery method may be associated with a lower incidence of anticholinergic adverse events compared with both the immediate-release and the extended-release oral formulations of traditional agents, as well as the most recently approved agents - trospium chloride, solifenacin and darifenacin. Much is still being learned about the function and specificity of muscarinic receptors, which will support the development of agents with sustained efficacy and enhanced tolerability compared with the available formulations to date. These include the S-isomer of oxybutynin, as well as selective muscarinic M2 receptor antagonists.Drug Safety 02/2005; 28(7):583-600. · 3.41 Impact Factor
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ABSTRACT: Forty-one children, aged 5-15 years, were referred because of recurrent urinary infections and/or enuresis. They were examined prospectively by means of cystometry. CO2 cystometry revealed detrusor instability in 18 children (44%), but if complete reproducibility were to be requested in repeated tests, only 7 children (17%) would have presented instability. Detrusor instability was not significantly related to definite pathological changes in the urinary tract or to irritative bladder symptoms.Urologia Internationalis 02/1986; 41(3):196-8. · 1.07 Impact Factor
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ABSTRACT: To evaluate the efficacy and tolerability of tolterodine in children with an overactive bladder, treated in a single incontinence centre. A retrospective analysis of a database of a total of two hundred and fifty-six patients (175 boys and 81 girls, age range 3 years to 17 years, mean age 8.33 years) with urodynamically confirmed bladder overactivity was performed. All children received tolterodine tartrate (dose range of 0.5-4 mg orally). In group I (n=205) tolterodine tartrate replaced anticholinergic drugs (AC) (oxybutinin chloride or oxyphencyclimin hydrochloride). A subgroup of patients switched because of intolerance due to serious adverse events (60.4%) or because of lack of improvement in micturition variables (39.6%). In group II tolterodine was prescribed as initial therapy (n=51). Tolerability was assessed by a standardised questionnaire on adverse events at every outdoor clinic visit. Efficacy assessment was based on micturition diary variables, mean change of maximum bladder capacity and number of incontinence episodes/24 h. The mean treatment time was 9.32 months with a range from 1.5 months to 23.4 months. The final dose was 0.1mg/kg orally daily divided into two doses. In group I central nervous system disorders (81%) were the most common adverse events, 26.2% showed flushing, 12.2% accommodation problems and 25.2% had gastrointestinal complaints (constipation, encopresis, abdominal pain). Withdrawal of the non-selective antimuscarinic drug resulted in total recovery from adverse events. Introduction of tolterodine in group I and II caused no serious adverse events. Nine patients (3.5%) reported side-effects and only two discontinued treatment. There were no reports of flushing, troubles of visual accommodation, hyperpyrexia. In group I we observed a mean decrease in urgency by 38.7%, a mean increase in maximal bladder capacity by 33.6% and the number of incontinence episodes decreased by 64.8%. In group II we observed equivalent values with a significant (p<0.001) change in maximal bladder capacity (49.7%), incontinence episodes (64.8%) and micturition episodes/24 h. The results of this retrospective analysis suggest that tolterodine is well tolerated in children and offers an effective treatment for urinary symptoms due to overactive bladder. Tolterodine is superior to non-selective antimuscarinic drugs, with respect to adverse events, allowing more compliance and more effective treatment in children.European Urology 02/2004; 45(2):240-4. · 10.48 Impact Factor