Keita Hirai1,2, Tatsuki Shimomura1, Hideaki Moriwaki3, Hidetoshi Ishii1,4, Takayuki Shimoshikiryo1, Daiki Tsuji1,2, Kazuyuki Inoue1,2, Toshihiko Kadoiri4, Kunihiko Itoh5,6. 1. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan. 2. Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan. 3. Department of Cardiology, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan. 4. Department of Pharmacy, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan. 5. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan. itohk@u-shizuoka-ken.ac.jp. 6. Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan. itohk@u-shizuoka-ken.ac.jp.
Abstract
PURPOSE: 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 95 patients (25.6 %), of whom 71 (19.1 %) 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 233 patients, of whom 123 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 24 of these patients (10.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age ≥75 years. CONCLUSIONS: 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.
PURPOSE: 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 95 patients (25.6 %), of whom 71 (19.1 %) 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 233 patients, of whom 123 were administrated tolvaptan for more than 1 month. Hypernatremia occurred in 24 of these patients (10.3 %) (late onset). Predictive factors for late onset of hypernatremia were an average daily dosage of tolvaptan >7.5 mg and age ≥75 years. CONCLUSIONS: 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.
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