Risk factors for adverse events in analgesic drug users: results from the PAIN study

Background The relative influence of various risk factors for adverse events (AE) in analgesics users have never been precisely quantified. Advantage was taken of data generated in the paracetamol, aspirin and ibuprofen new tolerability (PAIN) study, a large randomized double‐blinded trial of paracetamol, aspirin or ibuprofen for common pain in general practice to attempt this. Objective Identify and quantify factors associated with the occurrence of AE in users of analgesic drugs. Method Multivariate logistic regression analysis of potential risk factors for all AE, clinically significant AE (SAE) and clinically significant gastro‐intestinal AE (GI SAE). Results Of the 8677 patients included in the study, 8633 contributed data. The main risk factors for SAE were indication: compared to those treated for musculoskeletal pain, patients treated for menstrual pain had an odds ratio (95% Confidence Interval) of 0.4 (0.2–0.7), sore throat 0.6 (0.5–0.8), cold and flu 0.7 (0.6–0.8), headache 0.8 (0.7–1.0); concomitant use of medication contra‐indicated in the drugs' labeling (OR: 2.2; 1.6–2.9); increasing number of other concomitant medications: 1: OR 1.5 (1.3–1.8); 2–3: OR 1.9 (1.6–2.3); more than 3: OR (2.7; 2.1–3.5); treatment with aspirin: OR 1.4; (1.2–1.6) but not ibuprofen: OR 0.9; (0.8–1.1) compared to paracetamol; history of previous GI disorder OR 1.4 (1.0–1.8); female gender: OR 1.3 (1.1–1.4). Age was not significantly associated with AE in the multivariate analysis. Risk factors for all AE and GI SAE were mostly the same as for significant AE, but there were fewer GI SAE with ibuprofen than with paracetamol (OR 0.8; 0.6–0.9). Conclusion Apart from the analgesic used and its indication, the main risk factors identified for AE in users of first‐line analgesics for common pain were the number and nature of concomitant medication. Copyright © 2003 John Wiley & Sons, Ltd.