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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: January 30, 2014.



Naltrexone is a synthetic opioid antagonist used in prevention of relapse of opiate adiction and alcoholism. Naltrexone has been associated with low rates of serum enzyme elevations during therapy and with rare instances of clinically apparent liver injury.


Naltrexone (nal trex' one) is orally available opioid antagonist which blocks the euphoric effects of administered opiates. Naltrexone is a relatively pure antagonist and has no analgesic activity. Naltrexone has been shown to aid in maintenance of an opioid-free state in detoxified patients and to help in other addictions. Naltrexone was approved for use in the therapy of opioid and alcohol dependence in the United States in 1984. Naltrexone is available in tablets of 50 mg in several generic formulations and under the brand name Revia. More recently, injectable suspensions of naltrexone (Vivitrol) and solutions of methylnaltrexone (Relistor) have become available. The usually recommended dose of the oral preparation is 50 mg daily. The injectable suspension is given intramuscularly and the solution subcutaneously every 4 weeks. Naltrexone must be started carefully in patients with opioid abuse to avoid precipitous withdrawal reactions. The most common side effects are headache, sleep disturbance, anxiety, dizziness, nausea, diarrhea and rash.


Naltrexone therapy is typically given to patients with a high background rate of liver disease (injection drug use or alcoholism) and has been associated with variable rates of serum enzyme elevations (0% to 50%), values above 3 times the upper limit of normal occurring in approximately 1% of patients and occasionally leading to drug discontinuation. However, several studies have shown that the rate of ALT elevations during naltrexone therapy is similar to that with placebo. Most serum aminotransferase elevations during naltrexone therapy are mild and self limiting, resolving even with continuation of therapy. While several rare instances of acute, clinically apparent liver disease have been reported in patients taking naltrexone, the role of the medication in the liver injury has not always been clear and there has been no clear description of the clinical features of the injury. Thus, while often considered hepatotoxic, naltrexone has not been definitively linked to cases of clinically apparent liver injury.

Mechanism of Injury

Naltrexone is a relatively pure opioid antagonist and is rapidly metabolized by the liver to inactive forms. The cause of hepatic injury is not known, but may be partially dose dependent direct toxicity.

Agents in clinical use in therapy of alcohol abuse and dependence include acamprosate, disulfiram, methadone, and naltrexone.

Drug Class: Substance Abuse Treatment Agents; Opioid Antagonists

Other Drugs in the Class, Opioid Antagonists: Nalmefene, Naloxegol, Naloxone



Naltrexone – Generic, Revia®, Vivitrol®


Substance Abuse Treatment Agents; Opioid Antagonists


Product labeling at DailyMed, National Library of Medicine, NIH


Naltrexone Chemical Structure


References updated: 30 January 2014

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    (Controlled trial of 6 months of naltrexone by monthly depot injection in 624 patients with alcohol dependence, found no differences in mean ALT or bilirubin levels, but GGT levels were lower on naltrexone; ALT elevations occurred in 9-12% of those on naltrexone vs 15% on placebo).
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  • Tetrault JM, Tate JP, McGinnis KA, Coulet JL, Sullivan LE, Bryant K, Justice AC, Fiellin DA; for the Veterans Aging Cohort Study Team. Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone. Alcohol Clin Exp Res 2011; Jul 28. ePUB. [PMC free article: PMC3221963] [PubMed: 21797892]
    PubMed Citation (Retrospective analysis of the Veterans Administration database revealed 114 patients with HIV infection who were treated with naltrexone for alcohol dependence for at least 7 days [57% with HCV co-infection, 52% on antiretroviral therapy] showed that ALT levels remained low during naltrexone therapy and only 2 patients had elevations possibly related [Case 1, ALT 225 U/L at day 30 falling to baseline within 2 months of stopping: Case 2, ALT 152 U/L 33 days after stopping, resolving within 4 months]).
  • Vergara-Rodriguez P, Tozzi MJ, Botsko M, Nandi V, Altice F, Egan JE, O'Connor PG, et al; BHIVES Collaborative. Hepatic safety and lack of antiretroviral interactions with buprenorphine/naloxone in HIV-infected opioid-dependent patients. J Acquir Immune Defic Syndr 2011; 56: suppl 1: S62-7. [PubMed: 21317596]
    PubMed Citation (Among 141 HIV infected subjects treated with buprenorphine/naloxone for 6 months, median serum ALT and AST values did not change and no patient developed clinically apparent liver injury; 3 had transient ALT elevations during treatment [383, 123 and 218 U/L], but all resolved either spontaneously or with drug discontinuation).
  • Mitchell MC, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs 2012; 73: 991-7. [PubMed: 23036218]
    (Among 250 opiate dependent patients with high rates of hepatitis C and HIV infection treated with monthly injections of naltrexone or placebo, ALT elevations >3 times ULN occurred in 20% of naltrexone vs 13% of placebo recipients, but all resolved even with continuing the medication).


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