To explore risk factors for desmopressin-induced hyponatraemia and evaluate the impact of a serum sodium monitoring plan.
This was a meta-analysis of data from three clinical trials of desmopressin in nocturia. Participants received placebo or desmopressin orally disintegrating tablet ([ODT], 10-100 μg). Incidence of serum sodium <130 mmol/L was recorded by age, sex and dose. Potential predictors of clinically significant hyponatraemia were identified using multivariate analysis in a Cox proportional hazards model.
Dose, age, baseline serum sodium level and kidney function as estimated by eGFR clearance were significant risk factors for hyponatraemia in both sexes - similar to the known risk factors associated with hyponatraemia in the general population. In men, arthritis and use of drugs for bone disease were also predictive of hyponatraemia, while in women, raised monocytes and absence of lipid-modifying drugs increased the risk of hyponatraemia. Using the proposed monitoring scheme and the minimum effective dose would have omitted all patients with clinically significant hyponatraemia from further treatment.
Hyponatraemia is a recognised and well-understood risk of desmopressin therapy for nocturia. Its incidence can be reduced by using minimum effective gender-specific dosing with the ODT formulation (25 μg in women, 50 μg in men). A sodium monitoring plan is proposed whereby baseline sodium must be ≥135 mmol/L (especially important in the elderly), with additional monitoring at Week 1 and Month 1 for those at increased risk due to age ≥65 years or use of concomitant medication associated with hyponatraemia. This monitoring plan would help to prevent some at-risk patients developing hyponatraemia; retrospective application of the monitoring plan demonstrated that, once at-risk patients were appropriately screened out, only mild, non-clinically significant hyponatraemia was observed, within ranges of other drugs associated with hyponatraemia and similar to the background prevalence in the treatment population. This article is protected by copyright. All rights reserved.
BJU international. 2016 Jan 15 [Epub ahead of print]
Kristian Vinter Juul, Anders Malmberg, Egbert van der Meulen, Johan Vande Walle, Jens Peter Nørgaard
Clinical R&D, Ferring Pharmaceuticals A/S, Copenhagen, Denmark., Department of Paediatric Nephrology, University of Gent, Gent, Belgium.