Conivaptan for the Treatment of Severe Hyponatremia: Open‐Label Study Results

Background:

Hyponatremia is a common electrolyte disorder in hospitalized patients often resulting from elevated arginine vasopressin (AVP) levels. Conivaptan (CNV) is a novel AVP‐receptor antagonist that produces aquaresis, the solute‐free, electrolyte‐sparing excretion of water, by ing AVP V₂ receptors. The efficacy and safety of using CNV in the treatment of euvolemic and hypervolemic hyponatremia of various causes were investigated in a 4‐day, multicenter, open‐label study. The results for a subset of patients with severe hyponatremia, defined as serum sodium concentration ([Na⁺]) < 120 mEq/L are reported.

Methods:

Patients received a CNV 20‐mg intravenous loading dose, followed by a continuous 4‐day infusion of CNV 20 or 40 mg/day. The primary efficacy measure was area under the serum [Na⁺] time curve (AUC) from baseline to end of treatment. Secondary efficacy measures were also evaluated (see table). Of the 251 patients given treatment, 28 had a baseline serum [Na⁺] < 120 mEq/L.

Results:

Baseline serum [Na⁺] was similar in both treatment groups (see table). Both CNV doses increased serum [Na⁺] AUC and absolute serum [Na⁺] from baseline. Other secondary efficacy measures also showed improvement. A serum [Na⁺] correction was demonstrated on follow‐up day 34, with final mean serum [Na⁺] of 133.8 and 132.8 mEq/L in the 20 and 40 mg/day groups, respectively. CNV was well tolerated; infusion‐site phlebitis, hypokalemia, infusion‐site reaction, and hypotension were the most common adverse events. One patient in each group discontinued treatment because of an adverse event. Although 5 patients with severe hyponatremia experienced an overly rapid rise in serum [Na⁺], no patient had permanent neurological sequelae, such as osmotic demyelina‐tion syndrome.

TABLE — Efficacy of Conivaptan in Severe Hyponatremia

Conclusions:

CNV 20 and 40 mg/day increased serum [Na⁺] in patients with severe hyponatremia.

Author Disclosure:

S. Rosansky, None; L. E. Wagoner, None; J. G. Verbalis, Astellas Pharma US, Inc., consulting fees or other remuneration (payment); Otsuka Pharmaceutical Co., Ltd., consulting fees or other remuneration (payment); sanofi‐aventis, consulting fees or other remuneration (payment); B. McNutt, Astellas Pharma US, Inc., employment (full‐ or part‐time); N. Smith, Astellas Pharma US, Inc., employment (full‐ or part‐time); B. Yan, Astellas Pharma US, Inc., employment (full‐ or part‐time).