Toxicity of nonsteroidal anti-inflammatory drugs. An overview of the epidemiological evidence.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used throughout the world. This paper reviews the epidemiological data linking NSAID administration with gastrointestinal, hepatic, renal, haematological, and hypersensitivity reactions. Meta-analysis has demonstrated that NSAIDs are associated with serious upper gastrointestinal disorders, with a relative risk of 2.7 in patients receiving NSAIDs compared with subjects not receiving NSAIDs. An increase in the dose and duration of NSAIDs and age > 60 are associated with an increase in the risk of upper gastrointestinal toxicity. The current data strongly support a causal relationship between NSAIDs and gastrointestinal disorders. Case-control studies have demonstrated an association between some NSAIDs and neutropenia, with a relative risk of between 3 and 9 in patients treated with NSAIDs compared with nonusers of these drugs. NSAIDs have also been linked with hypersensitivity reactions, although the incidence of such reactions is very low. However, there are inconsistent data on the potential associations between NSAIDs and renal disease, and there are no epidemiological studies linking NSAIDs with acute liver disease. Overall, the incidence of serious adverse reactions associated with NSAIDs is low, and this class of drugs can be regarded as being reasonably safe.