Upper gastrointestinal complications among users of paracetamol.
Basic and Clinical Pharmacology and Toxicology 2006;98:297-303
ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) have been associated
with upper gastrointestinal complications (UGIC) such as bleeding or
perforation. Paracetamol has been traditionally considered a safer
alternative to NSAIDs. In a previous case-control study we found that
paracetamol at high doses increased the risk of UGIC. We proposed to
review all studies addressing the association between paracetamol and
UGIC and placed our results in the context of existing literature. We
conducted a nested case-control study using the United Kingdom General
Practice Research Database during the period between April 1993 and
October 1998. Then we performed a systematic review of the literature
indexed in MEDLINE published between 1980 and 2004. We identified a
total of twelve studies that assessed the association between
paracetamol and UGIC. We used a fixed effects model to calculate a
summary estimate of these studies. In the nested case control study,
use of paracetamol was associated with a small elevated risk of UGIC
(RR: 1.3; 95% CI, 1.1-1.5). The RR was 3.6 (95% CI, 2.6-5.1) among
paracetamol users of more than 2 grams daily, whereas smaller doses
did not carry an increased risk. Among the twelve studies identified
in the systematic review, estimates ranged from 0.2 through 2.0 with a
summary estimate of 1.3 (95% CI: 1.2-1.5). Our findings indicate that
use of paracetamol at the doses most commonly used confer little or no
increased risk of UGIC. More data are needed to confirm or refute the
suggestion that high dose paracetamol is associated with an increased
risk of UGIC of the same magnitude than the one observed with
traditional NSAIDs.