Hyponatremia is the most common
electrolyte disorder in clinical practice. Its incidence increases with age and it is associated with increased morbidity and mortality. Recently, the vaptans, antagonists of the
arginine vasopressin pathway, have shown promise for safe treatment of
hyponatremia. Here we evaluated the efficacy, safety, and tolerability of oral
lixivaptan, a selective
vasopressin V2-receptor antagonist, for treatment of nonhospitalized individuals with euvolemic
hyponatremia (
sodium less than 135 mmol/l) in a multicenter, randomized, double-blind, placebo-controlled, phase III study. About half of the 206 patients were elderly in a chronic care setting. Of these patients, 52 were given a placebo and 154 were given 25-100 mg per day
lixivaptan, titrated based on the daily serum
sodium measurements. Compared with placebo (0.8 mmol/l), the serum
sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 (primary efficacy endpoint) with
lixivaptan treatment. A significantly greater proportion of patients that received
lixivaptan achieved normal serum
sodium (39.4%) by day 7 relative to placebo (12.2%). Overall,
lixivaptan was considered safe and well-tolerated. Thus, oral
lixivaptan can be safely initiated in the outpatient setting and effectively increases serum
sodium concentrations in outpatients with euvolemic
hyponatremia.