Llewellyn David C, Oštarijaš Eduard, Sahadevan Sheyaam, Nuamek Thitikorn, Byrne Corrine, Taylor David R, Vincent Royce P, Dimitriadis Georgios K, Aylwin Simon Jb
Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Doctoral School of Clinical Medical Sciences, Medical School, University of Pécs, Pécs, Hungary; Faculty of Medicine, J. J. Strossmayer University of Osijek, Osijek, Croatia.
Endocr Pract. 2025 Apr;31(4):419-425. doi: 10.1016/j.eprac.2024.12.019. Epub 2024 Dec 27.
The recommended dose of tolvaptan for hyponatremia secondary to the syndrome of inappropriate antidiuretic hormone is 15 mg. We evaluated the efficacy of an initial 7.5 mg 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.
A retrospective review of patients with syndrome of inappropriate antidiuretic hormone treated in a single academic hospital in London. The initial dose was 7.5 mg and the second dose was 7.5 or 15 mg.
One hundred eighty-one patients were included. With the initial dose, the mean Na + increase was 4.54 ± 3.70 mmol/L (P < .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 < .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 were observed. For patients needing a second dose, the increment in Na + concentration showed no significant difference between 7.5 and 15 mg (P = .532).
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.