title: Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders.
abstract: BACKGROUND
  Many Japanese patients with hepatic disorders confirmed on diagnostic imaging and coexisting upper gastrointestinal (GI) peptic lesions receive treatment with proton pump inhibitors. Some pharmacotherapies used to treat peptic ulcers have been associated with adverse drug reactions (ADRs), including elevated liver enzyme levels.
  
  
  OBJECTIVE
  The aim of this study was to determine the tolerability and effectiveness of rabeprazole sodium in treating peptic lesions in patients with coexisting hepatic disorders.
  
  
  METHODS
  This open-label, practice-based, postmarketing surveillance investigation was conducted at 15 centers across Japan. Male and female patients aged ≥18 years with peptic lesions confirmed on upper GI endoscopy and with underlying hepatic disease were enrolled. Patients were randomly assigned to receive rabeprazole 10 or 20 mg PO (tablet) QD after a meal for up to 8 weeks. Tolerability was assessed using monitoring of the incidence of ADRs determined by direct patient questioning, spontaneous reporting, and laboratory assessment. All patients who received at least 1 dose of study drug were included in the tolerability assessment. Effectiveness was assessed at baseline and study end using the rates of achievement of improvement on endoscopy, relief of subjective/objective symptoms (rates of improvement in epigastric pain and heartburn), and global improvement. The effectiveness analysis included all patients with complete data before and after treatment. Subanalyses were conducted to determine the effectiveness of drug by identification of the proportion of patients with coexisting hepatic disorders (cirrhosis, chronic hepatitis, and other hepatic diseases [eg, alcoholic hepatitis, fatty liver]) and by peptic lesion (gastric ulcer, duodenal ulcer, stomal ulcer, and reflux esophagitis) who achieved improvement.
  
  
  RESULTS
  A total of 114 patients were enrolled; 108 patients were included in the tolerability analysis (81 men, 27 women; mean age, 59.9 years; 10-mg dose, 90 patients; 20-mg dose, 18 patients) and 98 patients were included in the analysis of effectiveness. Twenty-one ADRs occurred in 11 (10.2%) patients. Serious ADRs occurred in 2 patients (elevated bilirubin level and hepatic encephalopathy, 1 patient each). Administration of rabeprazole was discontinued in 5 patients due to the occurrence of the following ADRs: constipation (1 patient); epigastric pain (1); dyslalia, disorientation, tremor, sleep disorder, and hepatic encephalopathy (1); diarrhea (1); and elevated alkaline phosphatase and y-glutamyl transpeptidase levels (1). On endoscopy, the proportion of patients achieving improvement with either dose was 30/33 (90.9%). The relief rates assessed using subjective symptoms were 47/55 (85.5%) and 47/56 (83.9%) for epigastric pain and heartburn, respectively. The proportion of patients achieving global improvement with either dose was 80/98 (81.6%) patients (49/62 [79.0%] for cirrhosis, 11/16 [68.8%] for chronic hepatitis, and 20/20 [100.0%] for other hepatic diseases [alcoholic hepatitis, fatty liver]).
  
  
  CONCLUSIONS
  In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.
authors.affiliation: Second Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Makino
authors.affiliation: Second Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
authors.forename: Kimihide
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authors.lastname: Nakamura
authors.affiliation: Second Department of Internal Medicine, Asahikawa Medical College, Hokkaido, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Division of Gastroenterology, Kanto Medical Center NTT EC, Tokyo, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Division of Gastroenterology, Kanto Medical Center NTT EC, Tokyo, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Sezai
authors.affiliation: Department of Internal Medicine, Tokyo- Kosei-nenkin Hospital, Tokyo, Japan.
authors.forename: Yusei
authors.initials: Y
authors.lastname: Ikeda
authors.affiliation: Department of Internal Medicine, Tokyo- Kosei-nenkin Hospital, Tokyo, Japan.
authors.forename: Wahei
authors.initials: W
authors.lastname: Shinmura
authors.affiliation: Department of Gastroenterology, Seirei Mikatahara General Hospital, Shizuoka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Watahiki
authors.affiliation: Department of Gastroenterology, Seirei Mikatahara General Hospital, Shizuoka, Japan.
authors.forename: Hideaki
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authors.lastname: Yamamoto
authors.affiliation: Department of Gastroenterology, Seirei Mikatahara General Hospital, Shizuoka, Japan.
authors.forename: Yayuki
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authors.lastname: Hioki
authors.affiliation: Department of Gastroenterology, Seirei Mikatahara General Hospital, Shizuoka, Japan.
authors.forename: Masao
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authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Takashi
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authors.lastname: Kumada
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Takashi
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authors.lastname: Honda
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Tomoo
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authors.lastname: Rikitoku
authors.affiliation: Department of Gastroenterology, Ogaki Municipal Hospital, Gifu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hisanaga
authors.affiliation: Third Department of Internal Medicine, Nora Medical University, Nora, Japan.
authors.forename: Hiroshi
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authors.lastname: Fukui
authors.affiliation: Third Department of Internal Medicine, Nora Medical University, Nora, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamao
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Hironaka
authors.initials: H
authors.lastname: Kawasaki
authors.affiliation: Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Tottori, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Hosoda
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Ehime University, Ehime, Japan.
authors.forename: Morikazu
authors.initials: M
authors.lastname: Onji
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Ehime University, Ehime, Japan.
authors.forename: Hidetaka
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authors.lastname: Matsui
authors.affiliation: Second Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
authors.affiliation: Second Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.affiliation: Second Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Kazuhiko
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authors.lastname: Oho
authors.affiliation: Department of Internal Medicine, Social Insurance Tagawa Hospital, Fukuoka, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Maekawa
authors.affiliation: Department of Internal Medicine, Social Insurance Tagawa Hospital, Fukuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Takagi
authors.affiliation: Department of Internal Medicine, Social Insurance Tagawa Hospital, Fukuoka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shakado
authors.affiliation: Department of Internal Medicine, Social Insurance Tagawa Hospital, Fukuoka, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakayama
authors.affiliation: Department of Internal Medicine, Fukuoka Prefectural Yanagawa Hospital, Fukuoka, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Gondo
authors.affiliation: Department of Internal Medicine, Fukuokaken Saiseikai Futsukaichi Hospital, Fukuoka, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Internal Medicine, Fukuokaken Saiseikai Futsukaichi Hospital, Fukuoka, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Kusaba
authors.affiliation: Department of Internal Medicine, Miyazaki Medical College Hospital, Miyazaki, Japan.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Tsubouchi
authors.affiliation: Department of Internal Medicine, Miyazaki Medical College Hospital, Miyazaki, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Hayashi
authors.affiliation: Department of Internal Medicine, Miyazaki Medical College Hospital, Miyazaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hori
authors.affiliation: Department of Gastroenterology, Kokura Memorial Hospital, Fukuoka, Japan.
authors.forename: Yozo
authors.initials: Y
authors.lastname: Iida
authors.affiliation: Department of Gastroenterology, Kokura Memorial Hospital, Fukuoka, Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Yutoku
authors.affiliation: Department of Gastroenterology, Kokura Memorial Hospital, Fukuoka, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Maetani
authors.affiliation: Department of Gastroenterology, Kokura Memorial Hospital, Fukuoka, Japan.
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Kubo
authors.affiliation: Department of Internal Medicine, Chubu Hospital, Miyazaki, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Miyata
keywords: chronic hepatitis; cirrhosis; duodenal ulcer; gastric ulcer; hepatic disorders; rabeprazole; reflux esophagitis; stomal ulcer; upper gastrointestinal lesions