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The gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs


Clinical bottom line:

Conventional NSAIDs are, associated with a high incidence of gastroduodenal toxicity. In patients needing NSAIDs, low toxicity NSAIDs should be prescribed preferentially and commenced at the lowest recommended dose. Gastroprotective prophylaxis should be considered for patients at high risk of toxicity using a proton pump inhibitor or misoprostol.

The prevalence of peptic ulceration in chronic NSAID users is 20 - 30% with gastric ulcers approximately six times more common than duodenal ulcers. Upper GI symptoms do not match GI pathology. At least 50% of NSAID users with dyspepsia have no significant mucosal abnormalities whereas 60% of life-threatening complicated ulcers induced by NSAIDs have no preceding symptoms.

Literature review:

Hawkins C, Hanks G W. The Gastroduodenal Toxicity of Nonsteroidal Anti-Inflammatory Drugs. A Review of the Literature. Journal of Pain and Symptom Management ; 2000; 20:140-151.

Though there are 106 references, no mention is made of how searches were conducted and criteria for selection of papers.


In five endoscopic studies comprising 2882 patients misoprostol in different doses was used versus placebo, sucralfate or ranitidine for primary prophylaxis of NSAID-induced peptic ulcers. Misoprostol was shown to be effective for the primary prophylaxis of both duodenal and gastric ulcers. GI side effects were dose-related, with up to 40% of patients reporting diarrhoea on the higher dose regimen.

Four RCTs (1822 patients) studies the role of omeprazole in prevention and healing of NSAID-induced duodenal injury only. Omperazole 20mg or 40mg was compared with ranitidine, misoprostol or placebo. Omeprazole was significantly more effective than ranitidine in healing established ulcers. Misoprostol appeared equally effective. There was no difference between the two doses of omeprazole. Omeprazole was better tolerated than misoprostol.


This overview does not follow standard systematic review methodology. The effectiveness of misoprostol should be weighed against its side effects notable diarrhoea.