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

Ramy M. Hanna, Juan Carlos Velez, Anjay Rastogi, Minhtri K. Nguyen, Mohammad K. Kamgar, Kyaw Moe, Farid Arman, Huma Hasnain, Niloofar Nobakht, Umut Selamet, Ira Kurtz

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Rationale & Objective: Euvolemic 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 Design: A retrospective chart review study comparing outcomes in patients with SIADH treated with 15 versus 7.5 mg of tolvaptan. Settings & Participants: Patients 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. Predictors: Tolvaptan dose of 7.5 versus 15 mg daily. Outcomes: Appropriate 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 Approach: Descriptive study with additional outcomes compared using t tests and F-tests (Fischer's Exact χ2 Test). Results: Among 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). Limitations: Small sample size, retrospective, and nonrandomized. Conclusions: Tolvaptan, 7.5 mg, daily corrects hyponatremia with similar efficacy and less risk for overcorrection in patients with SIADH versus 15 mg of tolvaptan.

Original languageEnglish
Pages (from-to)20-28
Number of pages9
JournalKidney Medicine
Volume2
Issue number1
DOIs
StatePublished - 1 Jan 2020
Externally publishedYes

Keywords

  • SIADH
  • Tolvaptan
  • hyponatremia
  • osmotic demyelination syndrome

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