Acamprosate Appears Safe for People With AUD and Liver Disease

WASHINGTON — Acamprosate (Campral) was safe to use in people with liver disease, a phase II study showed.

Among people with alcohol use disorder (AUD) and alcohol-associated liver disease, acamprosate was safe, well-tolerated, and showed the potential to be effective, reported Tiffany Wu, MD, of the Mayo Clinic in Rochester, Minnesota, at the annual Liver Meeting sponsored by the American Association for the Study of Liver Disease (AASLD).

Acamprosate is an N-methyl-D-aspartate glutamate receptor antagonist approved for AUD. It reduces alcohol cravings, helping to reduce or abstain from alcohol consumption. But no formal studies have shown safety and efficacy in patients with alcohol-associated liver disease, and many hepatology providers are hesitant to use the medication, said Wu.

The phase II study was small and “designed to look at safety,” Wu added. “The goal is to expand and do phase III trials.”

Since acamprosate is not metabolized by the liver, it’s thought to be potentially helpful for people with both AUD and liver disease.

Among 12 patients with confirmed AUD and alcohol-associated liver disease enrolled in the study, one of seven participants who completed 8 weeks of follow-up reported pruritus, which was cleared when the dose was lowered. One participant reported abdominal pain, which was determined not to be associated with the study drug. No other adverse events were reported in the 12-week treatment and 24-week follow-up.

Seven of 12 patients initiated treatment with acamprosate and five completed the 12-week treatment program. Two patients relapsed: one at week 3 and one at week 13.

The patient who relapsed early had a Penn Alcohol Craving Score of 15 at week 1 (a score of 0 indicates no craving) but continued acamprosate treatment and experienced a downtrend in craving scores. The person who relapsed at week 13 did not continue treatment and withdrew from the study.

All participants were 21 or older with a diagnosis of alcohol-associated liver disease (based on alcohol consumption history, clinical imaging, and lab data) and AUD based on DSM-5 criteria. They were abstinent from alcohol for at least 2 weeks but not more than 6 months before starting acamprosate treatment. All had moderate to severe liver disease, with the vast majority having Child-Pugh class B (50%) or C (41.7%) disease.

Patients were followed weekly to week 8, then followed with urine tests, blood work, and labs monthly to 6 months as part of the safety assessment. The trial ran from September 2020 to May 2022.

Seven participants initiated acamprosate treatment with a 333 mg dose three times daily for 3 months, which was increased to 666 mg three times a day after week 1. In the patient who presented with pruritus, the dose was reduced to 333 mg.

Median age of participants was 50. Males made up 41.7% of the group; 75% were white, 16.7% American Indian, and 8.3% Asian. Most people in the study (75%) were married and 25% had children at home. All participants said they had social support.

AUD family history was present in 83.3% of participants and 16.7% had legal issues related to alcohol. Most participants (75%) had previous AUD treatment and one had a history of abuse with another substance.

Acamprosate may be good for some patients and not for others, Wu pointed out. People who do not have cravings are unlikely to respond to this drug, she noted. “I don’t think we have a magic solution or one-size-fits-all; I think we’re learning patients need multiple modalities of treatment,” she said.

A combination of pharmacotherapy and behavioral therapy may be needed, “but we have limited information to know which patients need which,” she added. “This opens the idea of personalized medicine, which is really critical.”

The 2022 Liver Meeting has a focus on integrated treatment in liver disease not seen at prior meetings, Wu noted. “We are identifying a growing need for improved training for hepatology providers on addiction care, and conversely, more training for addiction providers on liver care,” she said. “That’s the direction we need to go in.”