title: Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty.
abstract: BACKGROUND
  Paracetamol, a commonly used simple analgesic, can be fatal in overdose. Case reports suggest liver damage may occur at therapeutic doses. In older and particularly frail patients, dose reduction of therapeutic paracetamol is recommended due to concerns of an increased risk of hepatotoxicity.
  
  
  OBJECTIVE
  This study aimed to investigate the effects of ageing and frailty on the safety of paracetamol in hospital inpatients commenced on short courses of the drug.
  
  
  METHODS
  An observational cohort study of young (18-55 years, n = 19), older (≥ 70 years) fit (n = 24) and older frail (n = 28) hospital inpatients. Treatment group participants commenced regular paracetamol (3-4 g/day) during their hospital admission, whereas the control group was not exposed to paracetamol. In both groups, plasma alanine aminotransferase (ALT) was measured at baseline and day 5, and risk factors for raised ALT were recorded. A random serum paracetamol concentration was measured at day 5 in the treatment group.
  
  
  RESULTS
  No older frail treatment participants had an abnormal day 5 ALT. Odds ratios for having a day 5 ALT above the upper limit of normal (ULN) with paracetamol use, compared with unexposed controls, were 3·7 [95% confidence intervals (CI): 0·32, 41·59] for older not frail participants and 2·5 (95% CI: 0·34, 18·3) for younger participants. Decreasing frailty score independently predicted a day 5 ALT above the ULN (P < 0·05). Day 5 serum paracetamol concentrations were highest in older frail participants (P < 0·005).
  
  
  CONCLUSIONS
  Higher paracetamol concentrations observed in frail older patients after 5 days of therapeutic paracetamol do not necessarily indicate an increased risk of hepatotoxicity.
authors.affiliation: Departments of Aged Care and Clinical Pharmacology, Royal North Shore Hospital, St Leonards, NSW, Australia.
authors.forename: S J
authors.initials: SJ
authors.lastname: Mitchell
authors.forename: S N
authors.initials: SN
authors.lastname: Hilmer
authors.forename: B P
authors.initials: BP
authors.lastname: Murnion
authors.forename: S
authors.initials: S
authors.lastname: Matthews
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000410:Alanine Transaminase / Q000097:blood; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use; D001315:Australia / Q000453:epidemiology; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D016330:Frail Elderly; D006760:Hospitalization; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D000410:Alanine Transaminase