title: Comparison of potentially hepatotoxic drugs among major US drug compendia.
abstract: BACKGROUND
  Although a large number of drugs include warnings or listed adverse reactions that describe reports of associated hepatotoxicity, the hepatotoxic risk is documented with different definitions in major drug compendia.
  
  
  OBJECTIVE
  The purposes of this study were to compare inclusion of potentially hepatotoxic drugs, and analyze the ratings of hepatotoxic risk among major drug compendia.
  
  
  METHODS
  To assess the risk of drug-associated hepatotoxicity, we used current literature of epidemiological studies and developed a 4-level rating scale of hepatotoxic drugs: 3, clear literature evidence of life-threatening hepatotoxicity; 2, multiple case reports or significant liver injuries; 1, no significant liver damage has been reported; and 0, no information. All drugs were evaluated using the 5 major US drug compendia: American Hospital Formulary Service (AHFS), United States Pharmacopeia Drug Information (USPDI), Facts and Comparisons (F&C), Physicians' Desk Reference (PDR), and Clinical Pharmacology (CP). Average rating scores were calculated as the sum of each drug rating score divided by the total number of drugs. One-way analysis of variance and independent t tests were conducted to compare the difference among the rating scores.
  
  
  RESULTS
  In total, 175 different drugs and 3 therapeutic classes with hepatotoxic effects were identified in the compendia, including 59 antineoplastics, 28 anti-infectives, 17 nonsteroidal anti-inflammatory drugs, 17 antipsychotics or phenothiazine derivatives, 9 angiotensin-converting enzyme inhibitors, 6 anticonvulsants, 4 histamine-2 receptor antagonists, and other drugs. Average rating scores were 1.65 for AHFS, 1.10 for USPDI, 1.27 for F&C, 1.34 for PDR, and 1.61 for CP (F=7.93, P<.0001). The risk categories were significantly different among compendia in 4 therapeutic classes of antipsychotics and/or phenothiazines (F=3.471, P=.011), nonsteroidal anti-inflammatory drugs (F=7.866, P<.0001), antineoplastics (F=2.476, P=.044), anti-infectives (F=2.003, P=.098), and angiotensin-converting enzyme inhibitors (F=38.125, P<.0001).
  
  
  CONCLUSIONS
  Rating scores of hepatotoxicity were significantly different among drug compendia. The different compendium put different emphasis on hepatotoxicity severity. Comprehensive evaluations of hepatotoxic-related drugs provide critical information for health practitioners.
authors.affiliation: University of Cincinnati College of Pharmacy, University of Cincinnati Medical Center, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA. jeff.guo@uc.edu
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Guo
authors.forename: Patricia R
authors.initials: PR
authors.lastname: Wigle
authors.forename: Kangsan
authors.initials: K
authors.lastname: Lammers
authors.forename: Oceana
authors.initials: O
authors.lastname: Vu
mesh_terms: D056486:Chemical and Drug Induced Liver Injury; D064420:Drug-Related Side Effects and Adverse Reactions; D004364:Pharmaceutical Preparations / Q000145:classification; D012014:Reference Books, Medical; D014481:United States
chemical_list: D004364:Pharmaceutical Preparations