title: FDA proposals to limit the hepatotoxicity of paracetamol (acetaminophen): are they reasonable?
abstract: Hepatotoxicity from paracetamol is of great concern because of the considerable number of patients who develop severe toxicity from this drug. A group of senior medical practitioners, academics and scientists were brought together on June 29 and 30, 2009 by the Food and Drug Administration of USA (FDA) with the aim of providing advice on how to limit the number of cases of hepatotoxicity due to paracetamol in USA. The most contentious recommendations were the reduction in the dose of paracetamol to 650 mg and the elimination of prescription combination products of paracetamol and opiates. The first recommendation indicates that many members of the committee consider, despite much evidence to the contrary, that therapeutic doses of paracetamol (up to 4 g daily) are associated with a significant incidence of hepatotoxicity. The second recommendation, if accepted by FDA, will require major changes in the therapeutic use of paracetamol and opiates. Adoption of these two recommendations may lead to the increased use of NSAIDs with the potential of increasing incidence of NSAIDs-related adverse reactions.
authors.affiliation: Department of Clinical Pharmacology, St Vincent's Hospital, Darlinghurst, NSW, 2010, Australia. g.graham@unsw.edu.au
authors.forename: Garry G
authors.initials: GG
authors.lastname: Graham
authors.forename: Richard O
authors.initials: RO
authors.lastname: Day
authors.forename: Andis
authors.initials: A
authors.lastname: Graudins
authors.forename: Anthoulla
authors.initials: A
authors.lastname: Mohamudally
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D026683:Advisory Committees; D000428:Alcohol Drinking / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004338:Drug Combinations; D004348:Drug Labeling / Q000331:legislation & jurisprudence; D004349:Drug Packaging / Q000331:legislation & jurisprudence; D004335:Drug and Narcotic Control; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D006801:Humans; D004366:Nonprescription Drugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D055553:Prescription Drugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D004366:Nonprescription Drugs; D055553:Prescription Drugs; D000082:Acetaminophen