Wei Zhang, MD, PhD: Naltrexone’s GI, Liver Safety for Alcohol Use Disorder Treatment

New research is providing clinicians with an overview of the gastrointestinal and hepatic safety profile of US Food and Drug Administration-approved drugs indicated for alcohol use disorder.

Findings from the pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database were presented at The Liver Meeting 2024 from the American Association for the Study of Liver Diseases (AASLD) in San Diego, California.

Currently, there are 3 FDA-approved therapies for the treatment of alcohol use disorder: disulfiram, acamprosate, and naltrexone. However, their use in clinical practice is often limited due to concerns about their safety profile in patients with alcohol-associated liver disease.

“When the FDA approves a medication, it puts out a caution about potential side effects,” Wei Zhang, MD, PhD, a transplant hepatologist at Massachusetts General Hospital and an assistant professor at Harvard Medical School, explained to HCPLive. “The research in alcohol use disorder patients with liver disease is very sparse. There's some recent data that suggests it could be safe, especially naltrexone, in patients with cirrhosis, but this data is not very robust, and that's why we wanted to look into whether there’s more evidence to support the use of naltrexone in patients with liver disease.”

To address this gap in research, investigators collected reports from the FAERS database from the first quarter of 2004 to the last quarter of 2023 for disulfiram, acamprosate, oral naltrexone, and intramuscular naltrexone (Vivitrol). A disproportionality analysis was performed to identify gastrointestinal and liver adverse events associated with the drugs by comparing them with the full drugs indicated for alcohol use disorder in the FAERS database.

A total of 891 reports on disulfiram, 985 reports on acamprosate, 7489 reports on oral naltrexone, and 17,617 reports on intramuscular naltrexone were collected for analysis. The most frequently reported gastrointestinal and liver side effects were elevated liver enzymes; vomiting; nausea; and abdominal pain.

The information component of all gastrointestinal adverse events had a median of 4.34 (95% CI, 4.07 to 4.54) in disulfiram; 0.92 (95% CI, -0.02 to 1.56) in acamprosate; -1.42 (95% CI, -2.49 to -0.69) in oral naltrexone; and -2.22 (95% CI, -2.94 to -1.72) in intramuscular naltrexone.

Disulfiram had a reporting odds ratio of 24.01 (95% CI, 11.23 to 51.85) in acute hepatic failure and 6.31 (95% CI, 4.69 to 8.41) in elevated liver enzymes, while acamprosate had a reporting odds ratio of 5.66 (95% CI, 1.64 to 15.73) in elevated ammonia levels and 4.86 (95% CI, 2.06 to 10.23) in elevated bilirubin levels.

Oral naltrexone had a reporting odds ratio of 3.08 (95% CI, 2.43 to 3.91) and intramuscular naltrexone had a reporting odds ratio of 2.37 (95% CI, 2.02 to 2.8) in nausea and vomiting. Investigators pointed out that while the reporting odds ratio of elevated liver enzymes was 0.48 (95% CI, 0.31 to 0.74) in oral naltrexone, it was 0.17 (95% CI, 0.13 to 0.22) in intramuscular naltrexone.

“I think as more and more evidence emerges, our addiction medicine providers, including addiction medicine, addiction psychiatry, primary care, and hepatologists should feel more and more comfortable in prescribing naltrexone in this population so that they can get treated in a timely manner and delay their disease progression,” Zhang said.

Reference

^{Young Hwang S, Zhang W. Gastrointestinal and liver adverse effects of medical treatments of alcohol use disorder: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database. Paper presented at: AASLD’s The Liver Meeting 2024. San Diego, California. November 15-19, 2024.}