Endocrine Abstracts

Background and aims: Tolvaptan at the current licensed dose of 15 mg is highly efficious in the treatment of hyponatraemia secondary to syndrome of inappropriate antidiuretic hormone (SIADH), but there is a significant risk of over-correcting and therefore the possibility of osmotic demyelination syndrome (ODS). We aimed to investigate the efficacy and safety of both initial and subsequent doses of sub-15 mg, and review the effects on quality of life, length of stay and also side effects.

Method: Systematic searches were performed across six databases. Our keywords and Medical Subject Heading (MeSH) search terms included: ‘hyponatremia OR hyponatraemia AND (SIADH OR Syndrome of Inappropriate ADH Secretion OR syndrome AND of AND Inappropriate AND ADH AND secretion) AND tolvaptan’.

Findings: 18 papers were available for data extraction. When tolvaptan was administered at an initial dose of below 15 mg, data could be extracted for 495 patients. The mean increase in sodium within 24 hours was 7.2 mmol/L (CI 6–8.4 mmol/l). 31% had an overcorrections of ≥ 10 mmol/L with an initial dose of 7.5 mg tolvaptan (CI 15-53%). Over-corrections of ≥ 12 mmol/L was seen in only 10% of patients (CI 3-20%). Assessment of subsequent doses suggests that continued use of sub-15 mg is effective and safe, with the increment in sodium being smaller compared to the initial dose and much reduced chances of over-correcting compared to the initial dose. There was insufficient evidence to comment on side effects and the effects on length of stay and quality of life.

Interpretation: Our analysis supports the use of sub-15 mg as the initial dose of tolvaptan. If the basal sodium is ≥ 125, or if the patient is frail or has risk factors for ODS, then 3.75 mg should initially be trialled. In other cases, 7.5 mg is sufficient. 7.5 mg can be given for subsequnt doses.