Hepatic Safety of Once-Monthly Injectable Extended-Release Naltrexone Administered to Actively Drinking Alcoholics

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 aminotrasferase, 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. Conclusion: Extended-release formulation of naltrexone does not appear to be hepatotoxic when taken at the recommended clinical doses in actively drinking alcohol-dependent patients.