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. 2006 Jan;67(1):1–20. doi: 10.1016/j.curtheres.2006.02.003

Postmarketing surveillance of rabeprazole in upper gastrointestinal peptic lesions in Japanese patients with coexisting hepatic disorders

Isao Makino 1,*, Kimihide Nakamura 1, Yoichi Sato 1, Yuzuru Sato 2, Shuichi Sezai 2, Yusei Ikeda 3, Wahei Shinmura 3, Hajime Watahiki 4, Hideaki Yamamoto 4, Yayuki Hioki 4, Masao Suzuki 4, Takashi Kumada 5, Takashi Honda 5, Tomoo Rikitoku 5, Yasuhiro Hisanaga 5, Hiroshi Fukui 6, Junichi Yamao 6, Hironaka Kawasaki 7, Akihide Hosoda 7, Morikazu Onji 8, Hidetaka Matsui 8, Michio Sata 9, Takuji Torimura 9, Kazuhiko Oho 9, Ryuichiro Maekawa 10, Yoshiyuki Takagi 10, Satoshi Shakado 10, Masafumi Nakayama 10, Kazuhisa Gondo 11, Hirofumi Fukushima 12, Taku Kusaba 12, Hirohito Tsubouchi 13, Katsuhiro Hayashi 13, Takeshi Hori 13, Yozo Iida 14, Kouki Yutoku 14, Noboru Maetani 14, Yoshitsugu Kubo 14, Yoshifumi Miyata 15
PMCID: PMC3965972  PMID: 24678081

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]).

Conclusion:

In this study in Japanese patients with hepatic disorders, rabeprazole was well tolerated and appeared effective for the treatment of upper GI peptic lesions.

Key words: rabeprazole, hepatic disorders, cirrhosis, chronic hepatitis, upper gastrointestinal lesions, gastric ulcer, duodenal ulcer, reflux esophagitis, stomal ulcer

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