Korean J Urol.  2014 Dec;55(12):828-833. 10.4111/kju.2014.55.12.828.

Efficacy, Tolerability, and Safety of Oxybutynin Chloride in Pediatric Neurogenic Bladder With Spinal Dysraphism: A Retrospective, Multicenter, Observational Study

• Lee JH
• Kim KR
• Lee YS
• Han SW
• Kim KS
• Song SH
• Baek M
• Park K

• KMID: 2070098
• DOI: http://doi.org/10.4111/kju.2014.55.12.828

Abstract

PURPOSE
Anticholinergics are a key element in treating neurogenic detrusor overactivity, but only limited data are available in the pediatric population, thus limiting the application to children even for oxybutynin chloride (OC), a prototype drug. This retrospective study was designed to provide data regarding the efficacy, tolerability, and safety of OC in the pediatric population (0-15 years old) with spinal dysraphism (SD).
MATERIALS AND METHODS
Records relevant to OC use for neurogenic bladder were gathered and scrutinized from four specialized clinics for pediatric urology. The primary efficacy outcomes were maximal cystometric capacity (MCC) and end filling pressure (EFP). Data on tolerability, compliance, and adverse events (AEs) were also analyzed.
RESULTS
Of the 121 patient records analyzed, 41 patients (34%) received OC at less than 5 years of age. The range of prescribed doses varied from 3 to 24 mg/d. The median treatment duration was 19 months (range, 0.3-111 months). Significant improvement of both primary efficacy outcomes was noted following OC treatment. MCC increased about 8% even after adjustment for age-related increases in MCC. Likewise, mean EFP was reduced from 33 to 21 cm H2O. More than 80% of patients showed compliance above 70%, and approximately 50% of patients used OC for more than 1 year. No serious AEs were reported; constipation and facial flushing consisted of the major AEs.
CONCLUSIONS
OC is safe and efficacious in treating pediatric neurogenic bladder associated with SD. The drug is also tolerable and the safety profile suggests that adjustment of dosage for age may not be strictly observed.

Keyword

Child; Neurogenic urinary bladder; Oxybutynin

MeSH Terms

Adolescent
Child
Child, Preschool
Drug Evaluation/methods
Female
Humans
Infant
Infant, Newborn
Male
Mandelic Acids/adverse effects/*therapeutic use
Muscarinic Antagonists/adverse effects/*therapeutic use
Retrospective Studies
Spinal Dysraphism/*complications
Treatment Outcome
Urinary Bladder, Neurogenic/*drug therapy/etiology/physiopathology
Urological Agents/adverse effects/*therapeutic use
Mandelic Acids
Muscarinic Antagonists
Urological Agents

Figure

• 

  FIG. 1 Comparison of maximal cystometric capacity (A), age adjusted maximal cystometric capacity (B), and end filling pressure (C) between pretreatment and posttreatment with oxybutynin chloride. Each value represents mean±standard deviation. *p<0.05. **p<0.01.

• 

  FIG. 2 The second efficacy parameters are depicted. Changes of bladder compliance (A) and incontinence status following the treatment of oxybutynin chloride (B) are seen.

Reference

1. Bauer SB, Hallett M, Khoshbin S, Lebowitz RL, Winston KR, Gibson S, et al. Predictive value of urodynamic evaluation in newborns with myelodysplasia. JAMA. 1984; 252:650–652.

2. Copp AJ, Stanier P, Greene ND. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 2013; 12:799–810.

3. Mourtzinos A, Stoffel JT. Management goals for the spina bifida neurogenic bladder: a review from infancy to adulthood. Urol Clin North Am. 2010; 37:527–535.

4. Frimberger D, Cheng E, Kropp BP. The current management of the neurogenic bladder in children with spina bifida. Pediatr Clin North Am. 2012; 59:757–767.

5. Edelstein RA, Bauer SB, Kelly MD, Darbey MM, Peters CA, Atala A, et al. The long-term urological response of neonates with myelodysplasia treated proactively with intermittent catheterization and anticholinergic therapy. J Urol. 1995; 154:1500–1504.

6. Goessl C, Knispel HH, Fiedler U, Harle B, Steffen-Wilke K, Miller K. Urodynamic effects of oral oxybutynin chloride in children with myelomeningocele and detrusor hyperreflexia. Urology. 1998; 51:94–98.

7. Cartwright PC, Coplen DE, Kogan BA, Volinn W, Finan E, Hoel G. Efficacy and safety of transdermal and oral oxybutynin in children with neurogenic detrusor overactivity. J Urol. 2009; 182:1548–1554.

8. Grigoleit U, Murtz G, Laschke S, Schuldt M, Goepel M, Kramer G, et al. Efficacy, tolerability and safety of propiverine hydrochloride in children and adolescents with congenital or traumatic neurogenic detrusor overactivity: a retrospective study. Eur Urol. 2006; 49:1114–1120.

9. Neveus T, von Gontard A, Hoebeke P, Hjalmas K, Bauer S, Bower W, et al. Committee of the International Children's Continence Society. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation . J Urol. 2006; 176:314–324.

10. Hjalmas K. Urodynamics in normal infants and children. Scand J Urol Nephrol Suppl. 1988; 114:20–27.

11. Franco I, Horowitz M, Grady R, Adams RC, de Jong TP, Lindert K, et al. Efficacy and safety of oxybutynin in children with detrusor hyperreflexia secondary to neurogenic bladder dysfunction. J Urol. 2005; 173:221–225.

12. Ellsworth PI, Borgstein NG, Nijman RJ, Reddy PP. Use of tolterodine in children with neurogenic detrusor overactivity: relationship between dose and urodynamic response. J Urol. 2005; 174(4 Pt 2):1647–1651.

13. Yoo DS, Han JY, Lee KS, Choo MS. Prescription pattern of oxybutynin ER in patients with overactive bladder in real life practice: a multicentre, open-label, prospective observational study. Int J Clin Pract. 2012; 66:132–138.

14. Bennett N, O'Leary M, Patel AS, Xavier M, Erickson JR, Chancellor MB. Can higher doses of oxybutynin improve efficacy in neurogenic bladder? J Urol. 2004; 171(2 Pt 1):749–751.

15. Bolduc S, Moore K, Lebel S, Lamontagne P, Hamel M. Double anticholinergic therapy for refractory overactive bladder. J Urol. 2009; 182:4 Suppl. 2033–2038.

16. Madhuvrata P, Singh M, Hasafa Z, Abdel-Fattah M. Anticholinergic drugs for adult neurogenic detrusor overactivity: a systematic review and meta-analysis. Eur Urol. 2012; 62:816–830.