Letters Paracetamol hepatotoxicity

Is paracetamol hepatotoxic at normal doses?

BMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f1519 (Published 12 March 2013) Cite this as: BMJ 2013;346:f1519
  1. Nicholas D Moore, clinical pharmacologist1,
  2. Ezgi Gulmez, associate professor in pharmacoepidemiology1,
  3. Patrick Blin, senior scientific officer1
  1. 1Department of Pharmacology, University of Bordeaux, Inserm U657-CIC-P005, 33076 Bordeaux, France
  1. nicholas.moore{at}pharmaco.u-bordeaux2.fr

We note that the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (Study of Acute Liver Transplantation) in the UK1—63 cases in 2005-07 (5.25 cases per quarter)—was the same as that reported by Hawton and colleagues.2

However, in the UK and the other European countries included in the SALT study, paracetamol had been used in the 30 days before the first symptoms in several acute liver failures that led to registration for transplantation (ALFT) not related to overdose. There were 24 cases in the UK and 49 in France, for example. Using the same criteria as for other “known hepatotoxic agents,” such as non-steroidal anti-inflammatory drugs (NSAIDs), we found that non-overdose paracetamol was associated with a three times higher rate of ALFT than all NSAIDs pooled, or individual NSAIDs such as diclofenac or nimesulide. This was true whether the denominator was in patient years or individual patients.3

Perhaps we should start looking into hepatotoxicity associated with paracetamol at normal doses? Does this have anything to do with chronic glutathione depletion and increased risk from other toxins, as was hypothesised for asthma?4

Is paracetamol like the postman: so obviously innocuous and commonplace that it becomes invisible?


Cite this as: BMJ 2013;346:f1519


  • Competing interests: The SALT study was requested and approved by the European Medicines Agency and funded by Helsin Healthcare, which had no part in its performance, publications, or this reply.