title: Paracetamol in therapeutic dosages and acute liver injury: causality assessment in a prospective case series.
abstract: BACKGROUND
  Acute liver injury (ALI) induced by paracetamol overdose is a well known cause of emergency hospital admission and death. However, there is debate regarding the risk of ALI after therapeutic dosages of the drug.The aim is to describe the characteristics of patients admitted to hospital with jaundice who had previous exposure to therapeutic doses of paracetamol. An assessment of the causality role of paracetamol was performed in each case.
  
  
  METHODS
  Based on the evaluation of prospectively gathered cases of ALI with detailed clinical information, thirty-two cases of ALI in non-alcoholic patients exposed to therapeutic doses of paracetamol were identified. Two authors assessed all drug exposures by using the CIOMS/RUCAM scale. Each case was classified into one of five categories based on the causality score for paracetamol.
  
  
  RESULTS
  In four cases the role of paracetamol was judged to be unrelated, in two unlikely, and these were excluded from evaluation. In seven of the remaining 26 cases, the RUCAM score associated with paracetamol was higher than that associated with other concomitant medications. The estimated incidence of ALI related to the use of paracetamol in therapeutic dosages was 0.4 per million inhabitants older than 15 years of age and per year (99%CI, 0.2-0.8) and of 10 per million paracetamol users-year (95% CI 4.3-19.4).
  
  
  CONCLUSIONS
  Our results indicate that paracetamol in therapeutic dosages may be considered in the causality assessment in non-alcoholic patients with liver injury, even if the estimated incidence of ALI related to paracetamol appears to be low.
authors.affiliation: Fundació Institut Català de Farmacologia, Universitat Autònoma de Barcelona, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Mònica
authors.initials: M
authors.lastname: Sabaté
authors.forename: Luisa
authors.initials: L
authors.lastname: Ibáñez
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Pérez
authors.forename: Xavier
authors.initials: X
authors.lastname: Vidal
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
authors.forename: Xavier
authors.initials: X
authors.lastname: Xiol
authors.forename: Antoni
authors.initials: A
authors.lastname: Mas
authors.forename: Carlos
authors.initials: C
authors.lastname: Guarner
authors.forename: Montserrat
authors.initials: M
authors.lastname: Forné
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.forename: José
authors.initials: J
authors.lastname: Castellote
authors.forename: Joaquim
authors.initials: J
authors.lastname: Rigau
authors.forename: Joan-Ramon
authors.initials: JR
authors.lastname: Laporte
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000328:Adult; D000369:Aged, 80 and over; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D007565:Jaundice / Q000139:chemically induced; D008099:Liver / Q000187:drug effects*; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen