Low-Dose Tolvaptan for the Treatment of Syndrome of Inappropriate Antidiuretic Hormone–Associated Hyponatremia: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Clinical Effectiveness and Safety
Authors' conclusion
Low-dose tolvaptan (3.75-7.5 mg) effectively increases the serum sodium level in SIAD-associated hyponatremia. We recommend initiating tolvaptan at 7.5 mg, or 3.75 mg in high-risk patients, with close monitoring of sodium levels. These findings support a lower starting dose than currently licensed, although randomized controlled trials are needed to confirm optimal dosing strategies.
Study context
- Population
- Patients with syndrome of inappropriate antidiuresis (SIAD)-associated hyponatremia; MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and Scopus searched from inception to February 2024
- Comparison
- Low-dose tolvaptan in SIAD-associated hyponatremia
- Tolvaptan <15 mgn = 495
- 7.5 mgn = 286
- Outcome
- Change in serum sodium and overcorrection rates
- Follow-up
- 24 hours
Methodological detailsdose-based subgroup analyses
- Dose-based subgroup analyses
Pooled result
As reported in the abstract
Tolvaptan <15 mg
7.2
95% CI 6.0–8.4 · mmol/L
7.5 mg
7.8
mean · 95% CI 6.2–9.4 · mmol/L
3.75 mg
7.1
mean · 95% CI 4.7–9.6 · mmol/L
Further pooled results
Secondary outcomes (adverse effects, LOS, quality of life)
- Data insufficient for meta-analysis
Safety
Overcorrection · 24 hours
- Overcorrection rate, increase ≥10 mmol/L in 24 h
- 31% (95% CI, 15%-53%)
- Overcorrection rate, increase ≥12 mmol/L in 24 h
- 10% (95% CI, 3%-20%)
Overcorrection in the 3.75-mg subgroup
- Insufficient data to review overcorrection rates
Osmotic demyelination syndrome
- Cases of osmotic demyelination syndrome reported
- 0
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Original publication
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