Tolvaptan for the treatment of hyponatremia and congestive heart failure

Vasopressin plays a central role in regulating body fluid homeostasis, serum osmolality and vascular tone. In response to elevated serum osmolality, vasopressin acts on V2 renal receptors increasing water reabsorption and causing serum sodium to decrease. Pathological conditions characterized by abnormally elevated vasopressin levels such as heart failure (HF) or syndrome of inappropriate antidiuretic hormone (SIADH) can result in hyponatremia. Tolvaptan is a new selective nonpeptide vasopressin V2 receptor antagonist that has shown to rapidly normalize serum sodium concentrations in hyponatremic patients. In patients with congestive heart failure (CHF) and symptoms of volume overload, tolvaptan prompted rapid free water elimination and improved short-term signs and symptoms of HF, although no effect on long-term mortality or HF-related morbidity was observed. Data from phase III studies including over 5,000 patients have demonstrated that tolvaptan is a safe and well tolerated vasopressin receptor antagonist, whose long-term use is not associated with adverse outcomes. Tolvaptan has been recently approved for the treatment of hyponatremia and a marketing authorization application has been filed for the treatment of CHF.