title: Low-dose desmopressin combined with serum sodium monitoring can prevent clinically significant hyponatraemia in patients treated for nocturia.
abstract: 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. Patients received placebo or desmopressin orally disintegrating tablet (ODT; 10-100 μg). The 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, according to estimated GFR 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. Use of the proposed monitoring scheme and the minimum effective dose would have omitted all patients with clinically significant hyponatraemia from further treatment.
  
  
  
  The incidence of hyponatraemia can be reduced by using minimum effective gender-specific dosing with the ODT formulation of desmopressin (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 elevated risk because they are aged ≥65 years or receiving concomitant medication associated with hyponatraemia. This monitoring plan would help to prevent some at-risk patients developing hyponatraemia; retrospective application of the monitoring plan showed 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.
authors.affiliation: Clinical R&D, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Kristian Vinter
authors.initials: KV
authors.lastname: Juul
authors.affiliation: Clinical R&D, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Malmberg
authors.affiliation: Clinical R&D, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Egbert
authors.initials: E
authors.lastname: van der Meulen
authors.affiliation: Department of Paediatric Nephrology, University of Gent, Gent, Belgium.
authors.forename: Johan Vande
authors.initials: JV
authors.lastname: Walle
authors.affiliation: Clinical R&D, Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Nørgaard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050034:Antidiuretic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007010:Hyponatremia / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D053158:Nocturia / Q000097:blood* / Q000188:drug therapy*; D012189:Retrospective Studies; D012964:Sodium / Q000097:blood*; D055815:Young Adult
chemical_list: D050034:Antidiuretic Agents; D012964:Sodium; D003894:Deamino Arginine Vasopressin
keywords: desmopressin; hyponatraemia; nocturia