title: Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study).
abstract: OBJECTIVE
  Loop diuretics and spironolactone are used in patients with hepatic edema, but they are sometimes associated with insufficient responses as well as adverse events. Tolvaptan, a vasopressin type 2 receptor antagonist, was approved for hepatic edema in 2013. A large-scale post-marketing surveillance study has been carried out to evaluate the effectiveness and safety of tolvaptan in real-world clinical settings.
  
  
  METHODS
  Patients with hepatic cirrhosis with insufficient response to conventional diuretics were enrolled. The observational period was up to 6 months. Changes in body weight and clinical symptoms were measured to evaluate effectiveness. The incidence of adverse drug reactions was summarized as a safety measure.
  
  
  RESULTS
  Of 970 patients enrolled, 463 were included in the safety analysis. Of this group, 340 were included in the effectiveness analysis. Decreases in body weight from baseline were -2.38 kg on day 7 and -3.52 kg on day 14. Ascites and bloated feeling was significantly improved within 14 days. The mean change in body weight depended on estimated glomerular filtration rate levels. The most frequently reported adverse drug reaction was thirst (6.9% of patients). Serum sodium level of ≥146 mEq/L was observed in 12 patients (2.7%).
  
  
  CONCLUSIONS
  In the real-world clinical setting, tolvaptan showed aquaretic effectiveness in patients with cirrhosis. The mean change in body weight depended on renal function. We recommend tolvaptan use for hepatic cirrhosis at a stage in which the renal function is maintained.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Yamaguchi University, Ube, Yamaguchi, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.affiliation: Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.affiliation: Department of Pharmacovigilance, Otsuka Pharmaceutical Co.Ltd., Osaka, Japan.
authors.forename: Moriyoshi
authors.initials: M
authors.lastname: Yasuda
authors.affiliation: Department of Pharmacovigilance, Otsuka Pharmaceutical Co.Ltd., Osaka, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Pharmacovigilance, Otsuka Pharmaceutical Co.Ltd., Osaka, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Bando
authors.affiliation: Department of Pharmacovigilance, Otsuka Pharmaceutical Co.Ltd., Osaka, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Fukuta
keywords: cirrhosis; fibrosis