Treatment of hyponatremia: the role of lixivaptan

Abstract

Hyponatremia is the most common electrolyte disorder and is associated with serious neurologic sequelae and increased mortality. Conventional treatment options for hyponatremia, such as fluid restriction, hypertonic saline, loop diuretics, demeclocycline or urea, are ineffective in the long-term. The present review considers the role of vasopressin receptor inhibitors (vaptans), focusing on lixivaptan, in the treatment of patients with euvolemic or hypervolemic hyponatremia. Lixivaptan is an oral selective V2 receptor inhibitor, which produces a significantly greater increase of serum sodium levels compared with placebo. These effects seem promising, but more trials are needed to examine whether the beneficial effect of lixivaptan on serum sodium concentration translates into clinical benefit in these patient populations.

Keywords::

• antidiuretic hormone
• heart failure
• hyponatremia
• lixivaptan
• sodium
• V2 receptor inhibitors
• vaptans
• vasopressin

Financial & competing interests disclosure

This review was conducted independently; no company or institution supported it financially. The authors have given talks, attended conferences and participated in trials and advisory boards sponsored by various pharmaceutical companies. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Hyponatremia is the most common electrolyte disorder in both hospitalized patients and community subjects and is associated with serious neurological sequelae and increased mortality.

• Conventional treatment options for hyponatremia, such as fluid restriction, hypertonic saline, loop diuretics, demeclocycline or urea, have been proven inefficient in the long term or difficult to sustain.

• The selective V2-receptor antagonists, also called ‘vaptans,’ represent the first targeted therapy of hyponatremia.

• These agents correct hyponatremia by producing a selective water diuresis without affecting sodium and potassium excretion (aquaretics).

• Lixivaptan is an oral selective V2-receptor antagonist, which effectively improves serum sodium concentrations compared with placebo in patients with euvolemic or hypervolemic hyponatremia.

• More research is needed to examine if the beneficial effects of lixivaptan on the serum sodium concentration lead to decreased morbidity or mortality in patients with hyponatremia.