Tolvaptan ( Samsca ), an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies.
A study has analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) to evaluate the efficacy and safety of Tolvaptan in this group.
Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators.
Subjects were randomized to receive oral placebo ( n=52 ) or Tolvaptan 15 mg daily, with further titration to 30 and 60 mg daily, if necessary, based on the response of serum [ Na(+) ] ( n=58 ).
In patients with SIADH, improvement in serum [ Na(+) ] was significantly greater ( P less than 0.0001 ) with Tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study, with minimal side effects of increased thirst, dry mouth, and urination.
Only 5.9% of Tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines.
After discontinuation of Tolvaptan, serum [ Na(+) ] declined to values similar to placebo.
A significant positive treatment effect favoring Tolvaptan on the physical component, and a near-significant trend on the mental component, was found using the SF-12 Health Survey.
Tolvaptan was associated with a significantly reduced incidence of fluid restriction.
In conclusion, results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group. ( Xagena )
Verbalis JG et al, Eur J Endocrinol 2011;164: 725-732