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

Abstract Rationale & Objective Euvolemic hyponatremia often occurs due to the syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Vasopressin 2 (V2) 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 of serum sodium overcorrection with 15 mg of tolvaptan in SIADH patients. Study design A retrospective chart review study comparing the outcomes in patients with SIADH treated with 15 mg versus 7.5 mg of tolvaptan. Settings and participants: Patients with SIADH who were treated with a very low dose of tolvaptan (7.5 mg) at a single center compared to patients using a 15 mg dose from patient level data from the observational study described previously. Predictors Tolvaptan dose of 7.5 mg versus 15 mg daily. Outcomes Appropriate response to tolvaptan, defined by an initial rise in serum sodium of >3 mEq/L, and overcorrection of serum sodium (>8 mEq/L per day, and > 10 mEq/day in sensitivity analyses). Analytical approach Descriptive study with additional outcomes compared using t-tests. Results Among 18 patients receiving 7.5 mg of tolvaptan, the mean rate of correction was 5.6 ± 3.1 mEq/L/day and 2 patients (11.1%) corrected their serum sodium by more than 8 mEq/L/day, with one of these rising by more than 12 mEq/L/day. Of those receiving tolvaptan 7.5mg, 14 had efficacy, with rises of ≥ 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 mg tolvaptan versus 7.5 mg tolvaptan (11 of 28 versus 2 of 18, p=0.05 and 10 of 28 versus 1 of 18, p=0.03, for >8 mEq/L/day and >10 mEq/L/day, respectively). Limitations Small sample size, retrospective and non-randomized. Conclusions Tolvaptan 7.5mg daily corrects hyponatremia with similar efficacy and less risk of overcorrection in SIADH patients versus 15 mg tolvaptan.