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Hepatotoxicity risk factors and acetaminophen dose adjustment, do prescribers give this issue adequate consideration? A French university hospital study

  • Astrid Bacle
  • Charlotte Pronier
  • Helene Gilardi
  • Elisabeth Polard
  • Sophie Potin
  • Lucie-Marie ScailteuxEmail author
Pharmacoepidemiology and Prescription
  • 37 Downloads

Abstract

Background

The hepatotoxicity of acetaminophen is recognised worldwide. Unfavourable prognoses relating to overdose include liver transplantation and/or death. Several hepatotoxicity risk factors (HRFs) should motivate the adjustment of acetaminophen daily intake (to < 4 g/day): advanced age, weight < 50 kg, malnutrition, chronic alcoholism, chronic hepatitis B and C and HIV infection, severe chronic renal failure and hepatocellular insufficiency.

Method

Over a 7-day period in Rennes University Hospital in December 2017, using DxCare® software, with an odds ratio estimation, we analysed all acetaminophen prescriptions, to assess to what extent the presence of HRFs altered the prescribers’ choice of acetaminophen dose (< 4 g/day versus 4 g/day).

Results

Among 1842 patients, considering only the first acetaminophen prescription, 73.7% were on 4 g/day. Almost half this population had at least 1 HRF. Whereas around 80% of the prescriptions in the < 4 g/day group were for patients with at least 1 HFR, only 53% of the prescriptions in the 4 g/day group concerned patients without HFRs (p < 0.001). Age > 75 and low weight were associated with the prescriber’s choice of dose. Neither chronic alcoholism nor hepatocellular insufficiency influenced the acetaminophen doses prescribed.

Conclusion

Considering the widespread use of acetaminophen and its favourable safety profile compared with other analgesic drugs, it appears urgent to remind prescribers of the maximum daily dose recommendations for acetaminophen for patients with HRFs, especially those with chronic alcoholism and hepatocellular insufficiency.

Keywords

Hepatotoxicity Acetaminophen Dose adjustment Risk factor 

Notes

Acknowledgements

Administrative, technical or material support was provided by Rennes Hospital University. We thank Jean-Paul Sinteff (Medical Information Departement, CHU Rennes) for the DxCare® software data extraction, and Adrien Turban, Anne-Sophie Michel, Justine Geffroy and Stephanie Ollivier for their help in the data collection.

Authors’ contribution

LMS and AB had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. SP, EP, LMS and AB were part of the study concept and design. All authors were a part in the acquisition, analysis or interpretation of data. Drafting of the manuscript was done by LMS. All authors took part in the critical revision of the manuscript for important intellectual content. LMS was a part in the statistical analysis.

Compliance with ethical standards

All data was collected in accordance with the French legislation on retrospective clinical studies, in accordance with the precepts established by the Helsinki declaration.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Pharmacy DepartmentCHU RennesRennesFrance
  2. 2.Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) - UMR_S 1085RennesFrance
  3. 3.Virology DepartmentCHU PontchaillouRennesFrance
  4. 4.Pharmacovigilance and Pharmacoepidemiology Centre, Pharmacology DepartmentCHU RennesRennesFrance
  5. 5.Univ Rennes, REPERES ([Pharmacoepidemiology and Heath Services Research]) - EA 7449RennesFrance

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