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Is There Still a Role for Desmopressin in Children with Primary Monosymptomatic Nocturnal Enuresis?

A Focus on Safety Issues

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Abstract

It has recently became apparent that severe primary monosymptomatic nocturnal enuresis (MNE) has a worse prognosis than generally believed, and may have major consequences on the well-being of the child, thus making treatment mandatory. Desmopressin is one of the most widely prescribed medications for MNE, and in this current opinion article we discuss the safety of desmopressin in children with this condition.

Following a US FDA request in December 2007 that the prescribing information for desmopressin nasal spray be updated, desmopressin spray is no longer indicated for the treatment of MNE or for use in patients at risk for hyponatraemia.

Multiple reports of hyponatraemia in patients with nocturia (mainly the elderly) led to an increased awareness of the risks associated with desmopressin. While the pathogenesis of hyponatraemia in those over 65 years of age relates more to changing renal water and solute handling, we believe that in the young, overdosing and insufficient fluid restriction are usually the major causes.

Hyponatraemia is most frequently reported when desmopressin is administered by nasal spray compared with the tablet formulation. This may simply reflect the fact that for more than 10 years the spray was the only available mode of administration in many countries. However, it may also reflect the higher biodisponibility and/or intraindividual variability of pharmacokinetics of the spray compared with the tablet. There are few serious adverse events reported for the melt formulation (oral lyophilisate), but as it has only recently become available on the market, it would be premature to conclude that it has a better safety profile.

We believe that desmopressin in all formulations has a good safety profile in children with MNE, provided that treatment is properly prescribed and monitored; improving the training of doctors and patients in the dose-response kinetics of the drug, teaching appropriate restriction of fluid intake and by encouraging the use of desmopressin within a narrow dose range (10–20 μg spray, 120–240 μg melt and 200–400 μg tablet) when used in primary-care settings. Titrating higher doses in therapy-resistant patients should probably be carried out in a specialized enuresis centre, and only after documenting adequate morning urinary diluting capacity.

In summary, the risk of hyponatraemia is exacerbated by misuse of the drug rather than an inherent danger associated with the drug, which in our opinion should be addressed with better education rather than withdrawal of a medication that has the potential to benefit children with nocturnal enuresis.

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Acknowledgements

No sources of funding were used to assist in the preparation of this current opinion article. J. Van de Walle is a member of the Safety Advisory Board of Ferring Pharmaceuticals. J. Van de Walle and C. Van Herzeele are investigators on the ongoing DRIP (A Study of Oral Desmopressin in Previously Untreated Children Aged 5 to 15 Years With Primary Nocturnal Enuresis) study, which is funded by Ferring Pharmaceuticals, and C. Van Herzeele is funded by a grant from Ferring Pharmaceuticals. Ann Raes has no conflicts of interest to declare that are relevant to the content of this current opinion article.

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  1. Department of Pediatric Nephrology, University Hospital Ghent, De Pintelaan 185, 9000, Ghent, Belgium

    Johan Van de Walle, Charlotte Van Herzeele & Ann Raes

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  1. Johan Van de Walle
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  2. Charlotte Van Herzeele
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  3. Ann Raes
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Correspondence to Johan Van de Walle.

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Van de Walle, J., Van Herzeele, C. & Raes, A. Is There Still a Role for Desmopressin in Children with Primary Monosymptomatic Nocturnal Enuresis?. Drug-Safety 33, 261–271 (2010). https://doi.org/10.2165/11319110-000000000-00000

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