Efficacy and safety of oral tolvaptan therapy in patients with the syndrome of inappropriate antidiuretic hormone secretion.

Abstract

OBJECTIVE:

Tolvaptan, an oral antagonist of the vasopressin V(2) receptor, has been found to improve hyponatremia in patients with mixed etiologies. This study 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.

DESIGN AND PATIENTS:

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).

RESULTS:

In patients with SIADH, improvement in serum [Na(+)] was significantly greater (P<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.

CONCLUSIONS:

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.

• Authors: Joseph G Verbalis, Suzanne Adler, Robert W Schrier, Tomas Berl, Qiong Zhao, Frank S Czerwiec, SALT Investigators
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 164 Issue 5 Pg. 725-32 (May 2011) ISSN: 1479-683X [Electronic] England
• PMID: 21317283 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzazepines
• Tolvaptan

Topics

• Administration, Oral
• Aged
• Benzazepines (administration & dosage, adverse effects)
• Dizziness (chemically induced)
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Inappropriate ADH Syndrome (blood, drug therapy, urine)
• Male
• Middle Aged
• Thirst (drug effects, physiology)
• Tolvaptan
• Treatment Outcome