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.