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Continuing Education Activity

Naltrexone is an opioid antagonist used to treat alcohol use disorder and opioid dependence. It is FDA-approved for alcohol misuse and opioid dependence treatment. Off-label use includes treatment of cholestatic pruritus in adults. Another clinical use for naltrexone is for opiate toxicity. This activity outlines the indications, mechanism of action, administration methods, important adverse effects, contraindications, monitoring, and toxicity of naltrexone, so providers can direct patient therapy to optimal outcomes when alcohol misuse and opioid misuse/toxicity is an issue.


  • Identify the mechanism of action of naltrexone.
  • Review the approved and off-label indications for naltrexone.
  • Summarize the contraindication and adverse effects of naltrexone.
  • Outline the importance of collaboration and communication among interprofessional team members to improve outcomes and treatment efficacy for patients who might benefit from naltrexone therapy.


Naltrexone is an opioid antagonist used to treat alcohol use disorder and opioid dependence. It was developed in 1963 and patented in 1967. In 1984, naltrexone received approval for medical use in the United States. While experimenting with rats at the University of Pennsylvania, Dr. Joseph Volpicelli first recognized naltrexone's potential to treat alcohol use disorder. The World Health Organization (WHO) estimates that over 75 million people had alcohol abuse or dependence worldwide. Naltrexone is a mu-opioid antagonist. It is FDA-approved for alcohol abuse and opioid dependence treatment.[1] Off-label use includes treatment of cholestatic pruritus in adults. Researchers are studying its use in patients with stimulant addiction, particularly for patients with polydrug dependence on opioids, heroin, and amphetamine.

Another clinical use for naltrexone is for opiate toxicity/addiction. Exogenous opioids include the commonly prescribed pain relievers such as hydrocodone, oxycodone, among others, and drugs of abuse such as heroin.[2] Heroin induces euphoria at much higher doses than those prescribed by medical providers to relieve pain. Heroin leads to addiction via the euphoria it induces in its abusers. Opioid overdose can lead to coma and respiratory compromise.  Opioids act mainly via the mu receptor, although they affect mu, delta, and kappa-opioid receptors. Synthetic opioid antagonists can modify the action of opioids on these receptors.[3] Naltrexone competes as an antagonist at opioid receptors and can be used to treat alcohol and opioid addiction.

Mechanism of Action

Medications used to treat alcohol and opioid addiction focus on altering their reinforcing effects on inducing euphoria.[4] Naltrexone is pharmacologically effective against alcohol and opioids by blocking the mu-opioid receptor. Endogenous opioids are involved in modulating alcohol and opioids by reinforcing their effects.[5] Naltrexone blocks the effect of opioids and prevents opioid intoxication and physiologic dependence on opioid users. Naltrexone also modifies the hypothalamic-pituitary-adrenal axis to suppress ethanol consumption.


Naltrexone is available as an oral tablet (50 mg), and the usual dose for alcohol treatment is 50 to 100 mg. Naltrexone formulation is also available for depot injection (380 mg). Naltrexone absorption is almost complete after oral administration but has an extensive first-pass effect. Naltrexone excretion is primarily through urine. After oral administration, the half-life is 4 hours, and following an intramuscular injection (IM), the half-life is 5 to 10 days.

The patient first needs detoxification from opioid dependence before starting naltrexone. If there is a possibility of opiate or alcohol withdrawal, the recommended approach is to try a naltrexone challenge test. One should start with 25 mg orally, and if there are no withdrawal symptoms observed, repeat the test in 1 hour and continue 50 mg, orally, every day. Naltrexone can be given three times a week at doses of 100 to 150 mg or as a depot form for monthly administration. Naltrexone is typically combined with alpha-2 agonist, which minimizes patient discomfort during the withdrawal stage to shorten the duration of opioid withdrawal. Another benefit of rapid opiate detoxification is the reduced time between opioid use and the commencement of sustained naltrexone treatment to prevent relapse. Rapid opiate detoxification completion rates using naltrexone and clonidine range from 75% to 81% compared to 40% for methadone and clonidine alone.

Studies have suggested that carriers of the G-allele may experience a higher level of craving and a stronger euphoria following alcohol use. Naltrexone, 50 to 150 mg per day orally, appears to shorten subsequent relapses, whether used in the oral form or as once per month 380-mg injection, especially in individuals with the G-allele of the AII8G polymorphism of the mu-opioid receptor.

Naltrexone can be given orally with or without food. Administration with food or after meals may minimize adverse gastrointestinal (GI) effects. Advise patients not to self-administer opioids while receiving naltrexone therapy. The IM form requires injection using provided needles for administration into the upper outer quadrant of the gluteal area; clinicians should avoid injection into the blood vessel.[6] Do not administer intravenously (IV), subcutaneously, or into fatty tissue. Because many patients with a substance-misuse disorder are non-compliant with the oral formula, the IM injection is recommended.[7] Data indicate that outcomes for patients with alcohol dependence who take naltrexone may be more favorable when using the IM formula.

Naltrexone maintenance combined with psychosocial therapy is effective in reducing heroin use, but medication adherence is low. Depot injection formulation lasting up to 4 weeks improves adherence, retention, and drug use markedly. Subcutaneous naltrexone implants in Russia, China, and Australia have doubled treatment retention and reduced relapse to half that of oral naltrexone.

Adverse Effects

Naltrexone may cause gastrointestinal irritation such as diarrhea, abdominal cramps, and in some studies, it shows clinically insignificant increases in blood pressure. Naltrexone can precipitate a withdrawal syndrome in patients with opioid use disorder characterized by dysphoria, irritability, and having signs of autonomic hyperactivity such as tachycardia, tremor, and sweating. Piloerection is often associated with opioid withdrawal, especially when stopping the drug suddenly. Clonidine, an alpha2-adrenergic agonist, can aid in detoxification by reducing the signs of autonomic hyperactivity.


Contraindications to naltrexone use are hypersensitivity reactions, including urticaria, angioedema, and anaphylaxis. Opioid dependence or current use of opioid analgesics, including partial agonists, acute opioid withdrawal, and failure to pass a naloxone challenge or positive urine screen for opioids are also contraindications to using naltrexone.

Pregnancy Implications

Naltrexone is classified as category C for use during pregnancy, which means that the risk to the fetus of adverse effects cannot be ruled out. There is limited research available related to the use of naltrexone during pregnancy. Animal reproduction studies have shown adverse effects. Practice guidelines recommend that if a female treated with naltrexone to treat opioid use disorder becomes pregnant, naltrexone therapy should terminate if the mother and the physician agree that the risk of relapse is low. Naltrexone should not be given to treat alcohol use disorder in pregnant women unless needed for the treatment of acute alcohol withdrawal. Other agents are recommended for acute alcohol withdrawal. Naltrexone is also present in breast milk, and considering the importance of treatment of the mother, there needs to be a decision made whether to discontinue breastfeeding or discontinue the drug.


Baseline and periodic liver function tests are necessary. Clinicians must monitor for opioid withdrawal. Also, one has to check injection sites for reactions following IM administration. Further, the patient has to be screened for depression and/or suicidal thinking. When taken chronically for years, it is safe and associated with few side effects such as headache, nausea, and abdominal pain. Patients infected with hepatitis B or C can take naltrexone without worsening their liver function. However, most providers refrain from prescribing the medication if liver function tests are 3 to 5 times above normal levels.


Monitor patients presenting with dyspnea and hypoxia as there have been a few cases of eosinophilic pneumonia reported in the literature. Discontinue therapy if signs and symptoms of acute hepatitis develop. For patients undergoing surgery while on the treatment of opioid addiction, discontinue oral naltrexone for at least 72 hours before the scheduled surgery. The IM naltrexone should be suspended for at least 30 days before surgery.



Cases of hepatitis and liver dysfunction have been observed; transient asymptomatic hepatic transaminase elevations may also occur.


Reports exist of depression, suicidal ideation, and suicidal attempts.  Monitor the patient for symptoms of depression or suicidality.

Enhancing Healthcare Team Outcomes

Naltrexone's primary use is to manage alcohol and opioid dependence. An interprofessional team approach to naltrexone therapy will offer the best chance for optimal patient results. [Level 5]

The drug is best prescribed by healthcare professionals with experience in the field of drug abuse, psychiatry, and addiction. With many nurses working in outpatient psychiatry, they must know how this drug should be used and what precautions are required. Most of the patients with alcohol and opiate addiction managed with naltrexone need close monitoring but are manageable as outpatients. Data suggest that naltrexone can help reduce alcohol intake, but its benefits do not occur in everyone. Pharmacists can verify dosing, offer education on interactions and adverse effects, and help monitor the patient as treatment progresses. All team members must use open communication lines to inform others on the team of any concerns or possible changes in patient status. When it comes to opiate addiction, naltrexone has been shown to lower the frequency of negative drug tests. Still, relapse rates are high if the patient receives no adjunct behavior therapy.[8][9][10]

Article Details

Article Author

Dharminder Singh

Article Editor:

Abdolreza Saadabadi


8/6/2021 9:21:09 PM

PubMed Link:




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