Jeff J Guo1, Patricia R Wigle, Kangsan Lammers, Oceana Vu. 1. University of Cincinnati College of Pharmacy, University of Cincinnati Medical Center, 3225 Eden Avenue, Cincinnati, OH 45267-0004, USA. jeff.guo@uc.edu
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. OBJECTIVES: 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.
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. OBJECTIVES: 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.
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