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ISSUE 5 OCTOBER
Letters to the Editor

Naltrexone and liver disease

  • Mike McDonough, Philip Crowley

The Editorial Executive Committee welcomes letters, which should be less than 250 words. Before a decision to publish is made, letters which refer to a published article may be sent to the author for a response. Any letter may be sent to an expert for comment. When letters are published, they are usually accompanied in the same issue by their responses or comments. The Committee screens out discourteous, inaccurate or libellous statements. The letters are sub-edited before publication. Authors are required to declare any conflicts of interest. The Committee's decision on publication is final.

 

Letter to the Editor

In the good review on long-term drug treatment of patients with alcohol dependence (Aust Prescr 2015;38:41-3), the important issue of underuse of pharmacotherapy for alcohol dependence is identified and an outline of treatment is given. However, the article states that naltrexone is contraindicated in acute hepatitis or liver failure. In my clinical practice, varying degrees of chronic liver disease are commonly encountered when treating an alcohol-dependent population. Continued heavy drinking is much more likely to pose a greater risk to liver function than naltrexone. Arguably, the risk−benefit assessment likely favours naltrexone treatment. Naltrexone can be prescribed in patients with stable or compensated cirrhosis but is not recommended in acute liver failure. It carries a low risk of hepatotoxicity. However, in my experience, many potentially suitable patients are not given the drug because of concerns about hepatotoxicity.

Mike McDonough
Addiction Medicine
Western Health, Melbourne

Reference

Yen MH, Ko HC, Tang FI, Lu RB, Hong JS. Study of hepatotoxicity of naltrexone in the treatment of alcoholism. Alcohol 2006;38:117‑20.

 

Author's comments

Philip Crowley, the author of the article, comments

Precautions listed in naltrexone’s product information include saying it may cause hepatocellular injury when given in excessive doses, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. The product information also states that naltrexone is contraindicated in acute hepatitis or liver failure. This is based on a study in which 300 mg/day naltrexone was administered to obese patients. Five of 26 naltrexone recipients, and none of the placebo group, developed elevated serum transaminases after 3−8 weeks of treatment.1

Data on aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been used as an indicator of hepatotoxicity, with concentrations indicating both the effects of medication on hepatotoxicity, and reduced hepatotoxicity due to reduced alcohol consumption. Twelve of 1383 participants (0.9%) in the COMBINE study2 had elevated liver enzymes greater than five times the upper levels of normal. (Most cases were in the naltrexone group.) These effects resolved following discontinuation of the drug. This is the one study large enough to detect an adverse effect at this low level of incidence.

The study that Dr Mike McDonough refers to supports other smaller studies3,4 indicating that naltrexone was not hepatotoxic at the recommended dose in a trial of 74 participants.

I agree that often patients do better in a risk−benefit assessment when taking naltrexone compared to not taking it (because of concerns about minor liver enzyme changes).

 

References

  1. Croop RS, Faulkner EB, Labriola DF. The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. Arch Gen Psychiatry 1997;54:1130-5.
  2. Anton RF, O\u2019Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA 2006;295:2003-17.
  3. Brown ES, Carmody TJ, Schmitz JM, Caetano R, Adinoff B, Swann AC. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with bipolar disorder and alcohol dependence. Alcohol Clin Exp Res 2009;33:1863-9.
  4. Morley KC, Teesson M, Reid SC, Sannibale C, Thomson C, Phung N. Naltrexone versus acamprosate in the treatment of alcohol dependence: A multi-centre, randomized, double-blind, placebo-controlled trial. Addiction 2006;101:1451-62.

Mike McDonough

Addiction Medicine, Western Health, Melbourne

Philip Crowley

Addiction medicine specialist