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Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f403 (Published 07 February 2013) Cite this as: BMJ 2013;346:f403

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Re: Long term effect of reduced pack sizes of paracetamol on poisoning deaths and liver transplant activity in England and Wales: interrupted time series analyses

We are happy to see the number of registrations for hepatic transplantation for paracetamol overdose found in SALT (study of acute liver transplantation) (1) in the UK - 63 cases in 2005-2007, i.e. 5.25 cases per quarter - was the same as that reported here.

However, we also found in the UK and in the other European countries concerned by that study a number of acute liver failures leading to registration for transplantation not related to overdoses (ALFT), in which paracetamol was used within 30 days before the first symptoms of liver injury. This represents 24 cases in the UK, 49 in France, for instance. Using exactly the same criteria as for other "known hepatotoxic agents" such as NSAIDs, we found that non-overdose paracetamol was associated with three times more ALFT than all NSAIDs pooled, or individual NSAIDs such as diclofenac or nimesulide. This is true whether the denominator is in patients-years or individual patients (2).

Maybe one might start looking into hepatotoxicity associated with paracetamol at normal doses? Does this have anything to do with chronic glutathione depletion, too, and increased risk from other toxins, as was hypothesized for asthma?

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

1. Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, Jove J, et al. Transplantation for Acute Liver Failure in Patients Exposed to NSAIDs or Paracetamol (Acetaminophen) : The Multinational Case-Population SALT Study. Drug Saf. 2013. Epub 2013/01/18.
2. Moore N, Gulmez SE, Larrey D, Pageaux GP, Lignot S, Lassalle R, et al. Choice of the denominator in case population studies: event rates for registration for liver transplantation after exposure to NSAIDs in the SALT study in France. Pharmacoepidemiol Drug Saf. 2012. Epub 2012/11/21.
3. Shaheen S, Potts J, Gnatiuc L, Makowska J, Kowalski ML, Joos G, et al. The relation between paracetamol use and asthma: a GA2LEN European case-control study. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology. 2008;32(5):1231-6. Epub 2008/06/27.

Competing interests: The study cited was requested and approved by the European Medicines Agency and funded by Helsin Health care, which had no part in its doing, the publications or this reply.

11 February 2013
Nicholas D Moore
Clinical pharmacologist
Ezgi Gulmez, Patrick Blin
University of Bordeaux, INSERM U657 CIC-P0005
146 rue Leo Saignat, 33076 Bordeaux, France