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Advances in Therapy

, Volume 31, Issue 12, pp 1306–1316 | Cite as

Safety Profile of Desmopressin Tablet for Enuresis in a Prospective Study

  • Charlotte Van Herzeele
  • Pauline De Bruyne
  • Jonathan Evans
  • Paul Eggert
  • Henri Lottmann
  • Jens Peter Norgaard
  • Johan Vande Walle
Original Research

Abstract

Introduction

This pre-specified sub-study of the desmopressin response in primary nocturnal enuresis study (DRIP study) evaluates the safety profile of the oral desmopressin tablet in children with primary nocturnal enuresis. Endpoints are adverse events and change in body mass index.

Methods

The DRIP study was an open-label, intention-to-treat, phase IV, multi-national study. Overall, 936 patients were screened and 744 children aged 5–15 years with previously untreated primary nocturnal enuresis were eligible to receive the study medication desmopressin once daily as an oral tablet formulation. At each visit, adverse events were questioned and observed signs or symptoms were recorded.

Results

Overall, 222 (30%) patients experienced 404 treatment-emergent adverse events. The proportion of patients experiencing treatment-emergent adverse events was similar regardless of patient gender or age. Most treatment-emergent adverse events were experienced in three system organ classes: gastrointestinal disorders; infections and infestations; and respiratory, thoracic and mediastinal disorders and were considered unrelated to the study drug. There was a slight increase in body mass index from screening levels during the study, however, clinically not significant.

Conclusion

Desmopressin tablet treatment is well tolerated in children with primary nocturnal enuresis, regardless of patient gender or age.

Funding

The desmopressin response in primary nocturnal enuresis study (DRIP- study) was funded by Ferring.

Keywords

Children Desmopressin Enuresis Safety Tablet 

Notes

Acknowledgments

The desmopressin response in primary nocturnal enuresis study (DRIP study) was funded by Ferring. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. All named authors meet the ICMJE criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval for the version to be published.

Conflict of interest

C. Van Herzeele, J. Evans and P. Eggert declare that they have no actual or potential conflict of interest. P. De Bruyne received an independent Grant for Strategic Basic Research of the Agency for Innovation by Science and Technology in Flanders (IWT). H. Lottmann is a lecturer and advisor for Ferring Pharmaceuticals. J. Norgaard is a full time employee of Ferring Pharmaceuticals. J. Vande Walle is a lecturer, investigator and advisor for Ferring Pharmaceuticals.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki declaration of 1975, as revised in 2000 and 2008. Informed consent was obtained from all patients before being included in the study.

Supplementary material

12325_2014_173_MOESM1_ESM.pptx (205 kb)
Supplementary material 1 (PPTX 205 kb)

References

  1. 1.
    Hjalmas K, Arnold T, Bower W, et al. Nocturnal enuresis: an international evidence based management strategy. J Urol. 2004;171(6 Pt 2):2545–61.PubMedCrossRefGoogle Scholar
  2. 2.
    Neveus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol. 2010;183(2):441–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Glazener CM, Evans JH, Peto RE. Alarm interventions for nocturnal enuresis in children. Cochrane Database Syst Rev. 2005;2:CD002911.PubMedGoogle Scholar
  4. 4.
    Neveus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2006;176(1):314–24.PubMedCrossRefGoogle Scholar
  5. 5.
    Vande Walle J, Rittig S, Bauer S, et al. Practical consensus guidelines for the management of enuresis. Eur J Pediatr. 2012;171(6):971–83.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Glazener CM, Evans JH. Desmopressin for nocturnal enuresis in children. Cochrane Database Syst Rev. 2002;3:CD002112.PubMedGoogle Scholar
  7. 7.
    Djurhuus JC, Norgaard JP, Rittig S. Monosymptomatic bedwetting. Scand J Urol Nephrol Suppl. 1992;141:7–17 (discussion 8–9).PubMedGoogle Scholar
  8. 8.
    Van de Walle J, Van Herzeele C, Raes A. Is there still a role for desmopressin in children with primary monosymptomatic nocturnal enuresis?: a focus on safety issues. Drug Saf Int J Med Toxicol Drug Exp. 2010;33(4):261–71.CrossRefGoogle Scholar
  9. 9.
    Robson WL, Leung AK, Norgaard JP. The comparative safety of oral versus intranasal desmopressin for the treatment of children with nocturnal enuresis. J Urol. 2007;178(1):24–30.PubMedCrossRefGoogle Scholar
  10. 10.
    VandeWalle J, Stockner M, Raes A, Norgaard JP. Desmopressin 30 years in clinical use: a safety review. Curr Drug Saf. 2007;2(3):232–8.CrossRefGoogle Scholar
  11. 11.
    Robson WL, Norgaard JP, Leung AK. Hyponatremia in patients with nocturnal enuresis treated with DDAVP. Eur J Pediatr. 1996;155(11):959–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Lucchini B, Simonetti GD, Ceschi A, et al. Severe signs of hyponatremia secondary to desmopressin treatment for enuresis: a systematic review. J Pediatr Urol. 2013;9(6 Pt B):1049–53.PubMedCrossRefGoogle Scholar
  13. 13.
    Dehoorne JL, Raes AM, van Laecke E, Hoebeke P, Vande Walle JG. Desmopressin toxicity due to prolonged half-life in 18 patients with nocturnal enuresis. J Urol. 2006;176(2):754–7 (discussion 7–8).PubMedCrossRefGoogle Scholar
  14. 14.
    De Guchtenaere A, Raes A, Vande Walle C, et al. Evidence of partial anti-enuretic response related to poor pharmacodynamic effects of desmopressin nasal spray. J Urol. 2009;181(1):302–9 (discussion 9).PubMedCrossRefGoogle Scholar
  15. 15.
    Lottmann H, Baydala L, Eggert P, et al. Long-term desmopressin response in primary nocturnal enuresis: open-label, multinational study. Int J Clin Pract. 2009;63(1):35–45.PubMedCrossRefGoogle Scholar
  16. 16.
    Van Herzeele C, Alova I, Evans J, et al. Poor compliance with primary nocturnal enuresis therapy may contribute to insufficient desmopressin response. J Urol. 2009;182(4 Suppl):2045–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Juul KV, Klein BM, Sandstrom R, Erichsen L, Norgaard JP. Gender difference in antidiuretic response to desmopressin. Am J Physiol Renal Physiol. 2011;300(5):F1116–22.PubMedCrossRefGoogle Scholar
  18. 18.
    De Bruyne P, De Guchtenaere A, Van Herzeele C, et al. Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis. Eur J Pediatr. 2014;173(2):223–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2014

Authors and Affiliations

  • Charlotte Van Herzeele
    • 1
  • Pauline De Bruyne
    • 1
  • Jonathan Evans
    • 2
  • Paul Eggert
    • 3
  • Henri Lottmann
    • 4
  • Jens Peter Norgaard
    • 5
  • Johan Vande Walle
    • 1
  1. 1.Department of Pediatric NephrologyUniversity Hospital GhentGhentBelgium
  2. 2.Children’s Renal and Urology Unit, Nottingham Children’s HospitalNottingham University Hospitals NHS Trust, Queens, Medical Centre CampusNottinghamUK
  3. 3.Klinik f. Allgemeine PädiatrieUKSH, Campus KielKielGermany
  4. 4.Service de chirurgie viscérale pédiatriqueHôpital Necker-Enfants MaladesParisFrance
  5. 5.Ferring, Global Scientific affairs Urology Ferring International PharmaScience CentreCopenhagenDenmark

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