Efficacy and safety of low-dose tolvaptan (7.5mg) in the treatment of inpatient hyponatraemia: a retrospective study

Endocr Pract. 2024 Dec 27:S1530-891X(24)00879-6. doi: 10.1016/j.eprac.2024.12.019. Online ahead of print.

Abstract

Objectives: The recommended dose of tolvaptan for hyponatraemia secondary to SIADH is 15mg. We evaluated the efficacy of an initial 7.5mg dose and determined the frequency where sodium (Na+) correction exceeded safe limits, defined as an increment of ≥10 mmol/L, within the initial 8 or 24 hours of administration.

Methods: A retrospective review of patients with SIADH treated in a single academic hospital in London. The initial dose was 7.5mg and the second dose was 7.5 or 15 mg.

Results: 181 patients were included. With the initial dose, the mean Na+ increase was 4.54 ± 3.70 mmol/L (p < 0.0001) after 4-12 hours, with 8.7% demonstrating an increase exceeding 10 mmol/L. Between 18-30 hours, the mean Na+ increase was 6.15 ± 3.51 mmol/L (p < 0.0001), with 19.4% over-correcting. Over-correction was more likely in patients with a pre-dose Na+ concentration of ≤127 mmol/L (OR 13.64, 95% CI 1.80-102.95). No cases of osmotic demyelination syndrome (ODS) were observed. For patients needing a second dose, the increment in Na+ concentration showed no significant difference between 7.5 and 15mg (p = 0.532).

Conclusion: In our view, tolvaptan can be initiated with a 7.5 mg dose, accompanied by Na+ monitoring at 12 and 24 hours. If a second dose is necessary, 7.5 mg is comparably effective to a 15 mg dose, depending on the initial response. Further monitoring should include Na+ concentration at around 24 hours after the second dose.

Keywords: SIADH; hyponatraemia; over-correction; tolvaptan.