title: Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics.
abstract: BACKGROUND
  Hepatoxicity has been reported with oral naltrexone. Hepatic safety data were examined from a 6-month study evaluating the efficacy and safety of a now available extended-release formulation of naltrexone (XR-NTX) in patients with alcohol dependence.
  
  
  METHODS
  In all, 624 patients (68% male; median age of 44 years) were randomly assigned to XR-NTX 380 mg (n = 205), XR-NTX 190 mg (n = 210), or placebo (n = 209).
  
  
  RESULTS
  There were no significant differences in alanine aminotransferase, aspartate aminotransferase, or bilirubin levels between the study groups at study initiation or at subsequent assessments. Gamma-glutamyltransferase in the XR-NTX 380 mg group was lower compared with placebo at weeks 4, 8, 12, and 20. Both high (>3 times the upper limit of normal) liver chemistry tests (LCTs) and hepatic-related adverse events were infrequent in all study groups. In patients who were drinking heavily throughout the study, obese subjects, or those taking nonsteroidal anti-inflammatory drugs, there was no increase in frequency of high LCTs or hepatic-related adverse events in patients receiving XR-NTX (either dose) compared with placebo.
  
  
  CONCLUSIONS
  Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.
authors.affiliation: Section of Gastroenterology and Hepatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792-5124, USA. mrl@medicine.wisc.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lucey
authors.forename: Bernard L
authors.initials: BL
authors.lastname: Silverman
authors.forename: Ari
authors.initials: A
authors.lastname: Illeperuma
authors.forename: Charles P
authors.initials: CP
authors.lastname: O'Brien
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000473:pathology; D000437:Alcoholism / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D003692:Delayed-Action Preparations; D009271:Naltrexone