Drug Safety

, Volume 28, Issue 3, pp 227–240 | Cite as

Tolerability of Paracetamol

  • Garry G. GrahamEmail author
  • Kieran F. Scott
  • Richard O. Day
Review Article


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.


Paracetamol Therapeutic Dose Disulfiram Hypochlorous Acid Reactive Metabolite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors gratefully acknowledge discussions with Professor David Henry, Dr Richard Robson, Dr Robert Graham and Dr Bridin Murnion in the preparation of this article. A research project of Professor Graham has been supported by GlaxoSmithKline and Professor Day is a member of advisory boards for the companies marketing celecoxib (Pfizer and Pharmacia), rofecoxib (Merck) and paracetamol (acetaminophen) [GlaxoSmithKline]. Dr Scott is supported by the National Health and Medical Research Council of Australia (Grant no. 222870).


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Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • Garry G. Graham
    • 1
    Email author
  • Kieran F. Scott
    • 2
  • Richard O. Day
    • 1
  1. 1.Department of Clinical Pharmacology, St Vincent’s Hospital and Department of Physiology and PharmacologySchool of Medical SciencesSydneyAustralia
  2. 2.St Vincent’s Hospital Clinical SchoolUniversity of New South WalesSydneyAustralia

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