Janis C. Kelly
May 28, 2015
Acetaminophen (paracetamol) overdose caused one fifth of all cases of acute liver failure leading to the need for liver transplant (ALFT) in seven European countries, according to a study published online May 28 in the British Journal of Clinical Pharmacology. However, when researchers compared in-country rates of acetaminophen-linked AFLT they found a 200-fold variation on a per capita basis and a 20-fold variation by amount of drug sold.
Acetaminophen is “the almost exclusive cause for liver transplantation related to acute drug overdose,” write Sinem Ezgi Gulmez, MD, PhD, associate professor of pharmacology at the University of Bordeaux, France, and colleagues.
The analysis, based on data from the Study of Acute Liver Transplantation (SALT), showed an average event rate of one case of ALFT per 6 million inhabitants per year in the participating countries over the course of 3 years. The per capita rate was highest in Ireland, at one case for every 286,000 inhabitants, and lowest in Italy, at one case for every 180 million people. A similar variation was seen in frequency of liver failures for each ton of acetaminophen sold, at one ALFT event for every 20.7 tons of acetaminophen sold in Ireland compared with one for every 1074 tons sold in Italy.
The SALT study, which was performed at the request of the European Medicines Agency, examined nonsteroidal anti-inflammatory drug–associated ALFT in France, Greece, Ireland, Italy, Netherlands, Portugal, and the United Kingdom from 2005 through 2007. The data included all cases of ALFT identified from liver transplant registries that included 52 participating transplant centers (of 57 eligible) and comprised 9479 cases registered for liver transplantation.
51.5 tons per million inhabitants), and the lowest in Portugal (3.5 ton per million inhabitants), but the highest rates of overdose by ton of drug sold or per capita were in Ireland and the United Kingdom. Moreover, the between-country variation largely disappeared when investigators looked exclusively at nonoverdose cases of acetaminophen-related AFLT.
Dr Gulmez said in a press statement, “Since we do not have event rates for overdoses not leading to liver failure, we cannot conclude anything about the rates of non-ALFT overdoses in the different countries, but indicators point to more common use of paracetamol for self-poisoning in these countries.”
Dr Gulmez continued, “The differences in the figures for harm caused by paracetamol within different countries in Europe are not marginal, and suggest that there are some underlying causes. Paracetamol overdose is a serious public health issue and we should start looking into hepatotoxicity associated with paracetamol at normal doses.”
According to the authors, attempts to reduce acetaminophen overdosing by changing the amount per preparation or per box, restricting dispensing, and packaging such as blister packaging has been shown to reduce the number of intentional overdoses and referrals for liver transplantation.
The study was funded by Helsinn Healthcare SA. The authors have disclosed no relevant financial relationships.
Br J Clin Pharmacol. Published online May 28, 2015. Full text