Safety and Tolerability of Injectable Extended-Release Naltrexone for the Management of Alcohol Use Disorder in Advanced Alcohol-Associated Liver Disease.

Background: Pharmacologic treatment of alcohol use disorder (AUD) in patients with advanced alcohol-associated liver disease (ALD) remains underutilised due to concerns regarding hepatotoxicity. Injectable extended-release naltrexone (XR-NTX) may offer a safer alternative by avoiding first-pass hepatic metabolism, but data on its safety and effectiveness in patients with advanced ALD are limited.

Aim: To describe the clinical experience with XR-NTX in individuals with advanced ALD, evaluating its safety, tolerability and impact on liver function and alcohol use.

Methods: Retrospective case series of adults with ALD who received at least one dose of XR-NTX 380 mg IM at a tertiary care centre between 2023 and March 2025. Clinical data and laboratory tests were extracted from electronic health records over a minimum follow-up of 12 weeks. Safety was assessed based on adverse events and liver biochemistry. Alcohol use was evaluated using phosphatidylethanol (PEth) levels.

Results: Fourteen individuals with ALD were included (2 had F3 and 9 cirrhosis Child A-B). The median age was 51 [44-65] years, 64% were male, and median follow-up was 127 days. Four patients (29%) experienced mild adverse effects (injection site pain, nausea and vomiting, fatigue and sexual side effects); none had hepatotoxicity or hepatic decompensation. No significant changes in liver function tests or MELD/Child-Pugh scores were observed during the follow-up period. Eight participants (57%) had a decrease in alcohol consumption, with a non-significant decline in PEth levels.

Conclusion: In this case series, XR-NTX was well tolerated in patients with advanced ALD, without evidence of hepatotoxicity or liver decompensation.