Gastrointestinal safety of paracetamol: is there any cause for concern?

Paracetamol is classically considered as a very safe analgesic/antipyretic compound and, more specifically, as being virtually devoid of any gastrointestinal (GI) ulcerogenic potential. Accordingly, it is widely stated that paracetamol is particularly suitable for patients at high risk of developing GI ulcers or bleeds. This view has been challenged by recent epidemiological studies using computerised prescription data, which indicated that paracetamol exhibits dose-dependent GI toxicity. However, the results of these studies are most likely incorrect for reasons of inherent biases and confounding. Furthermore, their findings conflict with those of clinical trials and case-control studies in which information about drug exposure was obtained by direct questioning of both cases and controls. Finally, paracetamol, especially at high doses, may induce upper GI symptoms such as abdominal pain/discomfort, heartburn, nausea or vomiting. Conversely, the risk for ulcers and ulcer complications due to paracetamol is not supported by available data.