Lewellyn David, Nuamek Thitikorn, Ostarijas Eduard, Logan Ellis Hugh, Drakou Eftychia E, Aylwin Simon J B, Dimitriadis Georgios K
Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, United Kingdom.
Department of Endocrinology, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, England.
Endocr Pract. 2025 Jul;31(7):956-964. doi: 10.1016/j.eprac.2025.04.012. Epub 2025 Apr 25.
Tolvaptan at the licensed dose of 15 mg effectively treats syndrome of inappropriate antidiuresis (SIAD)-associated hyponatremia. However, concerns about overcorrection and osmotic demyelination syndrome have limited its adoption. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of lower tolvaptan doses (<15 mg) for treating SIAD-associated hyponatremia.
We systematically searched MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, and Scopus from inception to February 2024. The primary outcomes were change in serum sodium and overcorrection rates. The secondary outcomes included adverse effects, hospital length of stay, and quality-of-life measures. We conducted meta-analyses using mean differences for efficacy and proportions for safety outcomes, with dose-based subgroup analyses and meta-regression.
From 968 identified studies, 18 met inclusion criteria, comprising 495 patients. Initial doses below 15 mg increased the serum sodium level by 7.2 mmol/L (95% CI, 6.0-8.4) within 24 hours. In the 7.5-mg subgroup (n = 286), the mean increase was 7.8 mmol/L (95% CI, 6.2-9.4). The overcorrection rates were 31% (95% CI, 15%-53%) for an increase of ≥10 mmol/L and 10% (95% CI, 3%-20%) for an increase of ≥12 mmol/L in 24 hours. In the 3.75-mg subgroup, the mean increase was 7.1 mmol/L (95% CI, 4.7-9.6). There were insufficient data to review overcorrection rates. No cases of osmotic demyelination syndrome were reported. The secondary outcome data were insufficient for meta-analysis.
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.
托伐普坦以15毫克的许可剂量可有效治疗抗利尿激素分泌异常综合征（SIAD）相关的低钠血症。然而，对过度纠正和渗透性脱髓鞘综合征的担忧限制了其应用。我们进行了一项系统评价和荟萃分析，以评估较低剂量（<15毫克）托伐普坦治疗SIAD相关低钠血症的疗效和安全性。
我们从数据库建立至2024年2月，系统检索了MEDLINE、Embase、Cochrane CENTRAL、ClinicalTrials.gov和Scopus。主要结局为血清钠变化和过度纠正率。次要结局包括不良反应、住院时间和生活质量指标。我们使用疗效的均值差和安全性结局的比例进行荟萃分析，并进行基于剂量的亚组分析和荟萃回归。
在968项已识别的研究中，18项符合纳入标准，共495例患者。初始剂量低于15毫克可在24小时内使血清钠水平升高7.2毫摩尔/升（95%CI，6.0 - 8.4）。在7.5毫克亚组（n = 286）中，平均升高7.8毫摩尔/升（95%CI，6.2 - 9.4）。24小时内血清钠升高≥10毫摩尔/升时，过度纠正率为31%（95%CI，15% - 53%）；升高≥12毫摩尔/升时，过度纠正率为10%（95%CI，3% - 20%）。在3.75毫克亚组中，平均升高7.1毫摩尔/升（95%CI，4.7 - 9.6）。没有足够数据评估过度纠正率。未报告渗透性脱髓鞘综合征病例。次要结局数据不足以进行荟萃分析。
低剂量托伐普坦（3.75 - 7.5毫克）可有效提高SIAD相关低钠血症患者的血清钠水平。我们建议起始剂量为7.5毫克，高危患者为3.75毫克，并密切监测钠水平。这些发现支持采用低于当前许可的起始剂量，不过仍需随机对照试验来确定最佳给药策略。
