LAUSR

Objectives: The long-term efficacy of tolvaptan, a vasopressin V2 receptor antagonist, has been reported. However, the safety of long-term treatment remains to be fully elucidated. We assessed the safety profile of tolvaptan with respect to hypernatremia. Methods: This retrospective study included 371 patients treated with tolvaptan. Risk factors for hypernatremia (serum sodium concentration ≥ 147 mEq/L) were determined. Results: Hypernatremia occurred in 64 patients (25.6 %), of whom 45 (18.0 %) developed hypernatremia within 7 days of tolvaptan treatment (early onset). Stepwise logistic regression analysis demonstrated that baseline serum sodium ≥ 140 mEq/L, an initial tolvaptan dosage > 7.5 mg, and a BUN/serum creatinine ratio ≥ 20 were independent risk factors for early onset of hypernatremia. Tolvaptan was prescribed for more than 7 days to 163 patients, of whom 97 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 11 of these patients (11.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age ≥ 75 years. Conclusion: A daily dosage of 7.5 mg or less was recommended to prevent hypernatremia in short- as well as long-term tolvaptan treatment, and mainly elderly patients were at risk for hypernatremia.