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Large paracetamol overdose -- higher dose NAC is required - CON
  • Ruben Thanacoody
Ruben Thanacoody
Newcastle University

Corresponding Author:[email protected]

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Paracetamol overdose is common in developed countries but less than 10% involve large ingestions exceeding 30g or 500mg/kg. High dose acetylcysteine (NAC) has been proposed in patients taking large paracetamol overdoses based on reports of hepatotoxicity despite early initiation of NAC treatment with the commonly used 300 mg/kg intravenous acetylcysteine regimen. The evidence from cohorts of patients treated with the standard NAC regimen after large paracetamol overdoses shows that it is effective in most patients. Small studies in patients whose paracetamol concentration are above the 300mg/L nomogram line show that modification of the standard NAC regimen to provide a total of 400-500 mg/kg NAC over 21-22h may reduce the risk of hepatotoxicity (peak ALT>1000 IU/L) but the impact on development of hepatic failure, liver transplantation and mortality with this approach is presently unknown. Better risk stratification of patients taking paracetamol overdose may allow higher dose NAC and adjunctive treatments such as CYP2E1 inhibition and extracorporeal removal of paracetamol to be targeted to those patients at the highest risk of hepatotoxicity after a large paracetamol overdose.
11 Oct 2021Submitted to British Journal of Clinical Pharmacology
12 Oct 2021Submission Checks Completed
12 Oct 2021Assigned to Editor
16 Oct 2021Reviewer(s) Assigned
01 Nov 2021Review(s) Completed, Editorial Evaluation Pending
02 Nov 2021Editorial Decision: Revise Minor
12 Nov 20211st Revision Received
13 Nov 2021Submission Checks Completed
13 Nov 2021Assigned to Editor
13 Nov 2021Review(s) Completed, Editorial Evaluation Pending
22 Nov 2021Editorial Decision: Revise Minor
24 Nov 20212nd Revision Received
25 Nov 2021Submission Checks Completed
25 Nov 2021Assigned to Editor
25 Nov 2021Review(s) Completed, Editorial Evaluation Pending
30 Nov 2021Editorial Decision: Accept
23 Dec 2021Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15199