Tolvaptan 90mg tablets

OBJECTIVE Tolvaptan at the licensed dose of 15mg 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 (<15mg) for treating SIAD-associated hyponatremia. METHODS We systematically searched MEDLINE, EMBASE, Cochrane CENTRAL, ClinicalTrials.gov, SCOPUS from inception to February 2024. Primary outcomes were change in serum sodium and overcorrection rates. 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. RESULTS From 968 identified papers, 18 studies met inclusion criteria, comprising 495 patients. Initial doses below 15mg increased serum sodium by 7.2 mmol/L (95% CI: 6.0-8.4) within 24 hours. In the 7.5mg subgroup (n=286), the mean increase was 7.8 mmol/L (95% CI: 6.2-9.4). Overcorrection rates were 31% (95% CI: 15-53%) for ≥10 mmol/L and 10% (95% CI: 3-20%) for ≥12 mmol/L rise in 24 hours. In the 3.75mg subgroup, the mean increase was 7.1 mmol/L (95% CI: 4.7-9.6). There was insufficient data to review overcorrection rates. No cases of osmotic demyelination syndrome were reported. Secondary outcome data were insufficient for meta-analysis. CONCLUSION Low-dose tolvaptan (3.75-7.5mg) effectively increases serum sodium in SIAD-associated hyponatremia. We recommend initiating tolvaptan at 7.5mg, or 3.75mg in high-risk patients, with close monitoring of sodium levels. These findings support a lower starting dose than currently licensed, though randomized controlled trials are needed to confirm optimal dosing strategies.

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AimsSeveral diuretic strategies, including furosemide i.v. boluses (FB) or continuous infusion (FC), are used in acute heart failure (AHF).Methods and resultsWe systematically searched phase 3 randomized clinical trials (RCTs) evaluating diuretic regimens in admitted AHF patients within 48 h and irrespective of clinical stabilization. We calculated the odds ratio (OR) of FC or FB plus another diuretic (sequential nephron blockade, SNB) compared to FB alone on 24 h weight loss (WL) and worsening renal function (WRF), with a random-effects model with inverse variance weighting. Urine output, hypokalaemia, hyponatremia, and all-cause mortality/rehospitalization were secondary endpoints. In 25 selected RCTs (7149 patients, mean age 68.9 ± 8.7 years, mean left ventricular ejection fraction 38.2 ± 10.7%), FC [OR 1.55 (95% confidence interval 1.39-1.63)], FB plus tolvaptan [OR 1.57 (1.39-1.77)], FB plus SGLT2i [OR 1.23 (1.06-1.42)], and FB plus thiazide [OR 1.63 (1.37-1.94)] were associated with greater WL than FB. FB plus SGLT2i [OR 1.52 (1.19-1.94)] and FB plus acetazolamide [OR 1.81 (1.31-2.49)] were associated with WRF. FB plus thiazide was associated with both WRF [OR 1.78 (1.43-2.21)] and hypokalaemia [OR 1.69 (1.32-2.16)]. Results were consistent in sensitivity analyses considering urine output, RCTs protocol-established furosemide doses, or daily furosemide dose. Congestion/decongestion scores and clinical outcomes were reported in around 50% of RCTs. In an underpowered exploratory analysis, mortality/rehospitalization was non-significantly lower with SGLT2i [OR 0.45 (0.19-1.07)].ConclusionFC and SNB improve surrogates of response to FB in AHF. SNB is also connoted by WRF and may induce hypokalaemia. The endpoints of diuretic RCTs should be revised and harmonized.

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, with tolvaptan remaining the primary disease-modifying therapy. SGLT2 inhibitors have demonstrated robust renoprotection across the chronic kidney disease (CKD) spectrum, yet patients with ADPKD have been systematically excluded from pivotal trials due to concerns over vasopressin-mediated cystogenesis. This systematic review and meta-analysis aimed to pool available evidence on SGLT2 inhibitor use in patients with ADPKD. This systematic review and meta-analysis were registered with PROSPERO (CRD420261324155) and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta‑Analyses (PRISMA) guidelines. Five databases were searched through February 2026 for studies including ADPKD patients receiving any SGLT2 inhibitor. Quality was assessed using the Risk of Bias 2 (RoB2), Newcastle-Ottawa Scale, and Joanna Briggs Institute (JBI) tools, depending on the study design. Eight studies encompassing 3,180 patients were included, comprising one randomized controlled trial (RCT), one target trial emulation study, and six retrospective observational studies. In comparative analyses, SGLT2 inhibitor use was associated with a statistically significant attenuation of estimated glomerular filtration rate (eGFR) decline (pooled mean difference {MD}: 1.344 mL/min/1.73 m²/year; 95% CI: 0.836-1.852). A significant hemoglobin increase was observed in both comparative (MD: 0.66 g/dL) and single-arm analyses (MD: 0.55 g/dL). Subgroup analyses suggested a greater eGFR benefit in non-diabetic patients, though differences were not statistically significant. Our findings suggest that SGLT2 inhibitors may attenuate eGFR decline and improve hemoglobin in ADPKD, with the initial eGFR dip representing a class effect rather than harm, supporting their prospective evaluation in dedicated randomized trials. These findings should be interpretedwith cuchion the predominantly observational study designs, heterogeneous patient populations.

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