Equivalent Efficacy and Decreased Rate of Overcorrection in Patients With Syndrome of Inappropriate Secretion of Antidiuretic Hormone Given Very Low-Dose Tolvaptan

Abstract

Rationale & ObjectiveEuvolemic hyponatremia often occurs due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Vasopressin 2 receptor antagonists may be used to treat SIADH. Several of the major trials used 15 mg of tolvaptan as the lowest effective dose in euvolemic and hypervolemic hyponatremia. However, a recent observational study suggested an elevated risk for serum sodium level overcorrection with 15 mg of tolvaptan in patients with SIADH.Study DesignA retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan.Settings & ParticipantsPatients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared with patients using a 15-mg dose from patient-level data from the observational study described previously.PredictorsTolvaptan dose of 7.5 versus 15 mg daily.OutcomesAppropriate response to tolvaptan, defined as an initial increase in serum sodium level > 3 mEq/L, and overcorrection of serum sodium level (>8 mEq/L per day, and >10 mEq/L per day in sensitivity analyses).Analytical ApproachDescriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test).ResultsAmong 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L per day and 2 (11.1%) patients corrected their serum sodium levels by >8 mEq/L per day, with 1 of these increasing by >12 mEq/L per day. Of those receiving tolvaptan 7.5 mg, 14 had efficacy, with increases ≥ 3 mEq/L; similar results were seen with the 15-mg dose (21 of 28). There was a statistically significant higher chance of overcorrection with the use of 15 versus 7.5 mg of tolvaptan (11 of 28 vs 2 of 18; P = 0.05; and 10 of 28 vs 1 of 18; P = 0.03, for >8 mEq/L per day and >10 mEq/L per day, respectively).LimitationsSmall sample size, retrospective, and nonrandomized.ConclusionsTolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan.