Tolvaptan is an oral, once-daily nonpeptide
arginine vasopressin V(2)-receptor antagonist under development for the treatment of
hyponatremia and
congestive heart failure. In Phase II clinical trials,
tolvaptan, in addition to standard
therapy, increased fluid loss, resulting in decreased
body weight and improved
edema and serum
sodium without affecting blood pressure, heart rate or renal function in patients with
heart failure. The compound appeared to be well tolerated and dose-dependent adverse events were generally realated to its pharmacological activity, such as thirst and dry mouth. In patients with
hyponatremia,
tolvaptan appears to be more effective than fluid restriction at improving
sodium levels without an increase in adverse events. An international Phase III outcome study; Efficacy of
Vasopressin antagonism in
hEaRt failurE outcome Study with
Tolvaptan (EVEREST), evaluating the long-term efficacy and safety of
tolvaptan in patients hospitalized with worsening
heart failure, is currently ongoing.