Pediatric Pharmacology of Desmopressin in Children with Enuresis: A Comprehensive Review

• Published in: Paediatric drugs 2020-08, Vol.22 (4), p.369-383
• Main Authors: Gasthuys, Elke, Dossche, Lien, Michelet, Robin, Nørgaard, Jens Peter, Devreese, Mathias, Croubels, Siska, Vermeulen, An, Van Bocxlaer, Jan, Walle, Johan Vande
• Format: Article
• Language: English
• Subjects: Adenosine; Aquaporins; Bioavailability; Bioequivalence; Care and treatment; Causes of; Children; Children & youth; Congenital diseases; Desmopressin; Desmopressin acetate; Dosage and administration; Drug dosages; Enuresis; Food; Health aspects; Hemophilia; Internal Medicine; Kinases; Medicine; Medicine & Public Health; Methods; Pediatric pharmacology; Pediatrics; Pharmacodynamics; Pharmacokinetics; Pharmacotherapy; Polyuria; Review Article; Teenagers; Urinary incontinence; Urogenital system
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-020-00401-7

Desmopressin is a synthetic analogue of the natural antidiuretic hormone arginine vasopressin. Over the years, it has been clinically used to manage nocturnal polyuria in children with enuresis. Various pharmaceutical formulations of desmopressin have been commercialized for this indication—nasal spray, nasal drops, oral tablet and oral lyophilizate. Despite the fact that desmopressin is a frequently prescribed drug in children, its use and posology is based on limited pediatric data. This review provides an overview of the current pediatric pharmacological data related to the different desmopressin formulations, including their pharmacokinetics, pharmacodynamics and adverse events. Regarding the pharmacokinetics, a profound food effect on the oral bioavailability was demonstrated as well as different plasma concentration–time profiles (double absorption peak) of the desmopressin lyophilizate between adults and children. Literature about maturational differences in distribution, metabolism and excretion of desmopressin is rather limited. Regarding the pharmacodynamics, formulation/dose/food effect and predictors of response were evaluated. The lyophilizate is the preferred formulation, but the claimed bioequivalence in adults (200 µg tablet and 120 µg lyophilizate), could not be readily extrapolated to children. Prescribing the standard flat-dose regimen to the entire pediatric population might be insufficient to attain response to desmopressin treatment, whereby dosing schemes based on age and weight were proposed. Moreover, response to desmopressin is variable, whereby complete-, partial- and non-responders are reported. Different reasons were enumerated that might explain the difference in response rate to desmopressin observed: different pathophysiological mechanisms, bladder capacity and other predictive factors (i.e. breast feeding, familial history, compliance, sex, etc.). Also, the relapse rate of desmopressin treatment was high, rendering it necessary to use a pragmatic approach for the treatment of enuresis, whereby careful consideration of the position of desmopressin within this treatment is required. Regarding the safety of the different desmopressin formulations, the use of desmopressin was generally considered safe, but additional measures should be taken to prevent severe hyponatremia. To conclude the review, to date, major knowledge gaps in pediatric pharmacological aspects of the different desmopressin formulations still remain. Additiona