Evaluation of lixivaptan in euvolemic and hypervolemic hyponatremia and heart failure treatment.

ABSTRACT

INTRODUCTION: Lixivaptan is a selective vasopressin type 2 (V2) receptor antagonist that induces aquaresis, the electrolytes sparing excretion of water. Its ability to correct hyponatremia has been demonstrated in experimental animal studies as well as in clinical trials in humans. Recently, three Phase III, double-blind, randomized, placebo-controlled studies have been completed. In two studies, patients with euvolemic hyponatremia were enrolled, one in the inpatient and the other in the outpatient setting and the third study involved patients with hypervolemic hyponatremia hospitalized for decompensated heart failure (HF). The trials confirmed the efficacy of lixivaptan in raising serum sodium but raised concern about its safety in patients hospitalized with decompensated HF. AREAS COVERED The authors review original publications on lixivaptan and summarize their findings. Specifically, the authors present information regarding its structure, pharmacodynamics and kinetics, metabolism as well as its efficacy and safety in laboratory animals and human studies. Furthermore, the FDA website was accessed to obtain information presented at the September 13, 2012 meeting of the Cardiovascular and Renal Drugs Advisory Committee. EXPERT OPINION The published data indicate that lixivaptan raises sodium levels in hyponatremic patients and supports its use in patients with euvolemic hyponatremia. However, the authors note that more safety data are still needed specifically in patients with decompensated HF.