Fran Lowry

December 14, 2012

AVENTURA, Florida — Data from a phase IV hepatic safety study show no evidence of liver toxicity from buprenorphine/naloxone and methadone.

In the multicenter 24-week study of 731 patients in mild to moderate opioid withdrawal, those who were randomly assigned to receive 1 of the 2 study drugs showed no evidence of liver toxicity.

Dr. Andrew Saxon

During the early years of research on buprenorphine, before it was approved by the US Food and Drug Administration (FDA), there were concerns that it might, in some circumstances, have adverse effects on the liver, said Andrew J. Saxon, MD, from the Veteran's Affairs Puget Sound Health Care System, in Seattle, Washington.

"As part of the FDA approval process, the FDA required a phase IV postmarketing study of the effects of buprenorphine on the liver," Dr. Saxon told Medscape Medical News. "That was the impetus for the study; however, while the study did provide important information about liver health, a great deal more information about the differing effects of the 2 medications has also been revealed."

The study was conducted at 8 different sites that were part of the National Institute on Drug Abuse Clinical Trials Network. At each site, patients in mild to moderate opioid withdrawal were randomly assigned to treatment with either buprenorphine/naloxone (n = 340) or methadone (n = 391) for 24 weeks.

The patients gave at least 4 periodic blood samples for transaminase testing; weekly urine toxicology specimens were taken; and the patients were interviewed about their substance use and risk behavior.

At the end of 24 weeks, there was no evidence that either medication was harming the liver, Dr. Saxon reported.

The majority of participants (90%) began the study with the liver enzymes aspartate amino transferase (AST) and alanine amino transferase (ALT) values ≤2 times the upper limit of normal.

Subsequently, in 12.6% of patients receiving buprenorphine/naloxone and in 17.9% of patients receiving methadone, 1 or both levels increased >2 times the upper limit of normal; the difference between conditions was not statistically significant, Dr. Saxon said.

After controlling for medication condition, alcohol use, tobacco smoking, drug use, and needle sharing, the researchers found that infection with hepatitis B or C at baseline was the only significant predictor of increasing to >2 times the upper limit of normal or of extreme elevations in liver test results (hazard ratio, 2.40; 95% confidence interval, 1.46 - 3.92).

"Doctors can tell their patients that neither buprenorphine/naloxone or methadone have apparent liver toxicity and can prescribe either medication without major concern for liver injury," Dr. Saxon said.

Reckitt Benckiser Pharmaceuticals supplied the medications for this study. Dr. Saxon disclosed that he is a paid consultant to Reckitt Benckiser Pharmaceuticals.

American Academy of Addiction Psychiatry (AAAP) 23rd Annual Meeting & Symposium. Presented December 8, 2012.