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

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.
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Submitted on : Friday, July 5, 2019 - 3:11:58 PM
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Astrid Bacle, Charlotte Pronier, Helene Gilardi, Elisabeth Polard, Sophie Potin, et al.. Hepatotoxicity risk factors and acetaminophen dose adjustment, do prescribers give this issue adequate consideration? A French university hospital study. European Journal of Clinical Pharmacology, Springer Verlag, In press, ⟨10.1007/s00228-019-02674-5⟩. ⟨hal-02119177v1⟩

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