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.