Non-steroidal anti-inflammatory drugs(NSAIDs) are widely used for the treatment of many rheumatic diseases. Gastrointestinal ulcers are the most important complication during long-term NSAIDs therapy and sometimes, serious complications, such as perforation, stenosis, and bleeding occurs. Recently, use of COX-2 selective NSAIDs reduced such complications, however the increase of cardiovascular risks has been reported. Administration of misoprostol, one of the prostaglandin derivatives has been proven to be effective for both prevention and treatment of gastrointestinal ulcers associated with NSAIDs therapy and is recommended by the Japanese guidelines. In addition, the reduction of NSAIDs-related serious complications, such as perforation, stenosis, and bleeding have been reported with misoprostol therapy. The important side effects include abdominal pain, flatulence, and diarrhea.

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