Safety and Efficacy of Tolvaptan in Korean Patients with Hyponatremia Caused by the Syndrome of Inappropriate Antidiuretic Hormone

Background: The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).Methods: Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 +/- 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4.Results: Serum sodium increased significantly from baseline during the first 24 hours (126.8 +/- 4.3 vs. 133.7 +/- 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 +/- 3.8 vs. 135.6 +/- 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 +/- 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = -0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 +/- 4.8 mmol/L) than in moderate (6.4 +/- 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 +/- 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775-0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500-0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected.Conclusion: TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV.This study was funded by Korea Otsuka Pharmaceutical Co., Ltd. in 2012