Twelve case-control studies (7,894 cases) were included.
Users of paracetamol had a small increased risk of gastrointestinal complications; the overall summary RRs were 1.3 (95% CI: 1.2, 1.5) (fixed effect) and 1.4 (95% CI: 1.1, 1.6) (random-effects). Estimates of RR from individual studies ranged from 0.2 to 1.95.
No significant statistical heterogeneity was detected among the pooled studies (p=0.12). The funnel plot did not provide evidence of publication bias.
In the 3 studies that explored the association of daily dose of paracetamol and gastrointestinal complications, there was a gradient dose-effect with higher doses associated with more gastrointestinal complications. In one study, the adjusted RR was 1.0 (95% CI: 0.8, 1.2) for users of at most 1,000 mg/day (n=752), 0.8 (95% CI: 0.6, 1.1) for users of 1,001 to 1,999 mg/day (n=301), 1.9 (95% CI: 1.4, 2.6) for users of 2,000 mg/day (n=211), 3.4 (95% CI: 2.4, 4.8) for users of 2,001 to 3,999 mg/day (n=78), and 6.5 (95% CI: 2.4, 17.6) for users of at least 4,000 mg/day (n=20). In the other 2 studies, users of more than 20 tablets in the past week had an RR of 2.4 compared with non-users and users of >1000 mg/day had an adjusted RR of 2.6.