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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: March 24, 2020.



Naltrexone is a synthetic opioid antagonist used in prevention of relapse of opiate addiction 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), injectable implants and solutions of methylnaltrexone (Relistor) have become available for therapy of opioid dependence. Fixed combinations of naltrexone and bupropion (Contrave) have been approved as a weight loss agent. 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.

Likelihood score: E* (unproven but suspected cause 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 16590-41-3 C20-H23-N-O4 image 134993601 in the ncbi pubchem database


References updated: 24 March 2020

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    (Open label study of 12 weeks of oral naltrexone in 74 alcoholic patients; ALT levels decreased on naltrexone, but one patient had rise of ALT from 12 to 391 U/L; no details provided).
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    (Controlled trial of 8 weeks of depot naltrexone in 60 heroin dependent patients; ALT and GGT levels were stable; 2 patients with significant ALT elevations both had chronic hepatitis C).
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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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    (Among 24 patients undergoing alcohol withdrawal treated with high doses of naltrexone for 12 weeks, serum ALT and bilirubin levels did not change and GGT values fell slightly).
  • Tetrault JM, Tate JP, McGinnis KA, Coulet JL, Sullivan LE, Bryant K, Justice AC, Fiellin DA., Veterans Aging Cohort Study Team. Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone. Alcohol Clin Exp Res. 2012;36(2):318–24. [PMC free article: PMC3221963] [PubMed: 21797892]
    (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]
    (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).
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    (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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    (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, none of which were attributed to naltrexone or other opioid antagonist).
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    (Among 84 individuals with HIV infection recently released from prison who were treated for alcohol or opioid dependency with monthly injections of naltrexone or placebo, none developed clinically apparent liver injury but one subject with HCV co-infection discontinued naltrexone when ALT levels were found to have risen from 27 to 394 U/L after 4 injections).
  • Hernández N, Bessone F, Sánchez A, di Pace M, Brahm J, Zapata R, A, Chirino R, et al. Profile of idiosyncratic drug induced liver injury in Latin America: an analysis of published reports. Ann Hepatol. 2014;13:231–9. [PubMed: 24552865]
    (Among 176 reports of drug induced liver injury from Latin America published between 1996 and 2012, none were attributed to naltrexone or other opioid antagonist).
  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al. United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology. 2015;148:1340–52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]
    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, none were attributed to naltrexone or other opioid antagonist).
  • Chaignot C, Zureik M, Rey G, Dray-Spira R, Coste J, Weill A. Risk of hospitalisation and death related to baclofen for alcohol use disorders: Comparison with nalmefene, acamprosate, and naltrexone in a cohort study of 165 334 patients between 2009 and 2015 in France. Pharmacoepidemiol Drug Saf. 2018;27:1239–48. [PMC free article: PMC6282718] [PubMed: 30251424]
    (Analysis of the French Health Insurance claims database of patients initiating alcohol use disorder therapies found an increased risk of hospitalization [+13%] and death [+31%] compared to exposure to approved drugs such as acamprosate, naltrexone and nalmefene).
  • Opioids for pain. Med Lett Drugs Ther. 2018;60(1544):57–64. [PubMed: 29664446]
    (Concise review of the efficacy, safety and costs of opioids used for pain mentions that the 3 opioid antagonists that are used to treat opioid-induced constipation-methylnaltrexone, naloxegol and nalmedine-have similar degrees of efficacy and toxicities).


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