The excellent tolerability of therapeutic doses of
paracetamol (
acetaminophen) is a major factor in the very wide use of the drug. The major problem in the use of
paracetamol is its hepatotoxicity after an overdose. Hepatotoxicity has also been reported after therapeutic doses, but critical analysis indicates that most patients with alleged toxicity from therapeutic doses have taken overdoses. Importantly, prospective studies indicate that therapeutic doses of
paracetamol are an unlikely cause of hepatotoxicity in patients who ingest moderate to large amounts of alcohol. Controlled clinical trials have found that
paracetamol is very well tolerated by the gastrointestinal tract. While variable results have been found in case control studies, most studies have shown no change or a small increase in the relative risk of perforations,
ulcer or
bleeding in the upper gastrointestinal tract. However, associations between the use of
paracetamol and gastrointestinal toxicity, as well as with
chronic renal disease and
asthma, are very likely to reflect biases in some case control studies. In particular, such biases may be caused by the perceived high tolerability of
paracetamol in these diseases. The consequent use of
paracetamol in these diseases states then leads to an apparent association between
paracetamol and the disease. Despite metabolism of
paracetamol to reactive compounds,
hypersensitivity reactions are rare, although
urticaria occurs in occasional patients.
Paracetamol appears to be well tolerated during pregnancy although prospective studies are required.