title: Risk factors for hypernatremia in patients with short- and long-term tolvaptan treatment.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.|Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Shimomura
authors.affiliation: Department of Cardiology, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Moriwaki
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.|Department of Pharmacy, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shimoshikiryo
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.|Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, 422-8526, Japan.|Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Department of Pharmacy, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kadoiri
authors.affiliation: 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.|Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital, 4-27-1, Kita-ando, Aoi-ku, Shizuoka, 420-8527, Japan. itohk@u-shizuoka-ken.ac.jp.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006955:Hypernatremia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Diuretics; Heart failure; Hypernatremia; Liver cirrhosis; Tolvaptan