Risk of serious upper gastrointestinal toxicity with over-the-counter nonaspirin nonsteroidal anti-inflammatory drugs

Background & Aims: Use of prescription nonaspirin nonsteroidal anti-inflammatory drugs (NANSAIDs) increases the risk of serious upper gastrointestinal toxicity. Less is known about over-the-counter (OTC) NANSAIDs, which are typically used at lower doses and for shorter durations. This study assessed the risk of toxicity with OTC NANSAIDs. Methods: A total of 359 case subjects hospitalized for upper gastrointestinal bleeding, perforation, or benign gastric outlet obstruction were recruited from 28 hospitals. A total of 1889 control subjects were recruited by random digit dialing from the same region. Data on medication use were collected via structured telephone interview. Results: Use of OTC NANSAIDs on :4 days during the most recent week had an adjusted odds ratio (OR) of 1.83 (95% confidence interval [CI], 1.14 - 2.95). Use of high-dose OTC NANSAIDs during the index week had an adjusted OR of 5.21 (95% CI, 2.32 - 11.69). In contrast, use of OTC NANSAIDs < 4 times during the index week (adjusted OR, 0.67; 95% CI, 0.43 - 1.06) and use of very low doses of prescription or OTC NANSAIDs during the index week (adjusted OR, 0.74; 95% CI, 0.49 - 1.12) were not significantly associated with an increased risk of serious gastrointestinal toxicity. We did not observe a significant difference between the risk of toxicity with OTC naproxen versus OTC ibuprofen (adjusted OR, 0.84; 95% CI, 0.26 - 2.70). Conclusions: Use of OTC NANSAIDs at recommended doses has a relatively good safety profile compared with prescription NANSAIDs. However, use of high-dose OTC NANSAIDs (comparable to a prescription dose) is associated with serious gastrointestinal toxicity.