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Naltrexone (Monograph)

Brand names: ReVia, Vivitrol
Drug class: Opoid Antagonists
- Alcohol Deterrents
- Deterrents, Alcohol

Medically reviewed by on Jun 10, 2024. Written by ASHP.


    Hepatic Effects
  • Possible dose-related hepatotoxicity. Margin between therapeutic and hepatotoxic dosages may be less than fivefold; hepatotoxicity not apparent at usual dosages. (See Hepatic Effects under Cautions.)

  • Contraindicated in patients with acute hepatitis or liver failure; carefully weigh potential benefits against possible hepatotoxic risks in patients with active liver disease.

  • Instruct patients to discontinue naltrexone and contact a clinician if manifestations of acute hepatitis occur. (See Advice to Patients.)


Essentially a pure opiate antagonist.

Uses for Naltrexone

Opiate Dependence

Used as an adjunct to a medically supervised behavior modification program in the maintenance of opiate cessation (opiate-free state) in individuals who were formerly physically dependent on opiates and who have successfully undergone detoxification (designated an orphan drug by FDA for this use).

Behavior modification is an integral component in maintaining opiate cessation; behavior modification programs involve supervised programs of counseling, psychologic support and therapy, education, and changes in life-style (social rehabilitation).

May diminish or eliminate opiate-seeking behavior by blocking opiate euphoria and by preventing the conditioned abstinence syndrome (i.e., heightened sensitivity to stimuli, abnormal autonomic responses, dysphoria, intense opiate craving) that occurs following opiate withdrawal.

Efficacy in maintaining long-term cessation appears to be low; poor compliance appears to be the major limiting factor. Because noncompliance with naltrexone is not associated with unpleasant symptoms of withdrawal, compliance depends more on voluntary efforts; successful cessation may be more likely in highly motivated individuals.

Because of potential for relapse to opiate use and subsequent opiate overdosage, routinely discuss availability of the opiate antagonist naloxone with all patients receiving new or reauthorized prescriptions for medications for treatment of opiate use disorder (OUD); strongly consider prescribing naloxone for use in the event of an overdose in all such patients.

Has been used for rapid or ultrarapid detoxification in the management of opiate withdrawal [off-label] in opiate-dependent individuals, both in inpatient and outpatient settings.

Rapid opiate detoxification involves the administration of opiate antagonists (e.g., naltrexone and/or naloxone) to shorten the time period of detoxification.

Ultrarapid detoxification is similar but involves the administration of opiate antagonists while the patient is sedated or under general anesthesia. Consider the risk of adverse respiratory and cardiovascular effects associated with this procedure, as well as the costs of general anesthesia and hospitalization.

Alcohol Dependence

Management of alcohol dependence in conjunction with a behavior modification program involving supervised programs of counseling, psychologic support and therapy, and education and changes in life-style (social rehabilitation).

Used IM in individuals who are able to abstain from alcohol in an outpatient setting and are abstinent when treatment is initiated.

Behavior modification is an integral component in maintaining alcohol cessation; naltrexone has not been shown to provide any therapeutic benefit except as part of an appropriate plan of addiction management.

When used in conjunction with behavior modification, naltrexone reportedly decreases alcohol craving, reduces alcohol consumption, decreases the number of drinking days, maintains abstinence from alcohol ingestion, and prevents, decreases, or ameliorates the severity of relapse.

Naltrexone is not uniformly effective; the expected effect is a modest improvement in the outcome of conventional therapy.

Naltrexone Dosage and Administration


REMS for Parenteral Naltrexone

Verification of Opiate Abstinence Prior to Initiation of Therapy

Naloxone Challenge Test


Administer orally or by IM injection.

Do not administer parenteral preparation by IV or sub-Q injection; do not administer into fatty tissue.

Oral Administration

Administer orally; minimize adverse GI effects by taking with food or antacids or after meals.

Patients should take naltrexone as directed and not attempt self-administration of opiates during therapy with the drug. (See Risks Associated with Self-administration of Opiates During Naltrexone Therapy under Cautions.)

IM Administration

IM preparation may be used in individuals who are able to abstain from alcohol in an outpatient setting and are abstinent when treatment is initiated.

Administer by deep IM injection into the upper outer quadrant of the gluteal muscle every 4 weeks (or once a month); alternate buttocks for subsequent injections.

Administer only with needle and other components of dose pack supplied by manufacturer.

Use aspiration to avoid inadvertent injection into a blood vessel.

Do not administer by IV or sub-Q injection; do not inadvertently administer into fatty tissue. Inadvertent sub-Q injection may increase likelihood of severe injection site reactions. (See Local Reactions under Cautions.)

Evaluate the patient's body habitus prior to each injection to ensure that the 1.5-inch needle supplied by the manufacturer is adequate for gluteal IM injection in that patient. Consider alternative treatment for any patient whose body habitus (i.e., gluteal fat thickness) precludes IM injection with the provided needle.


Consult manufacturer’s labeling for instructions for using components of dose pack for reconstitution.

Allow dose pack to reach room temperature before reconstituting.

Reconstitute vial labeled as containing 380 mg of naltrexone extended-release microspheres with 3.4 mL of diluent; shake vigorously for 1 minute. Use only the diluent supplied by the manufacturer. Administer immediately.


Available for oral administration as naltrexone hydrochloride; dosage expressed in terms of the salt.

Available for IM administration as naltrexone.


Opiate Dependence
Induction of Therapy for Opiate Cessation

Initiate induction regimen following completion of opiate detoxification and verification that the patient is free of opiates. (See General under Dosage and Administration.)

Initially, 25 mg; if no evidence of withdrawal is present, begin 50 mg daily.

Alternatively, some clinicians have administered 12.5 mg initially, followed by incremental increases of 12.5 mg daily until the usual dosage of 50 mg daily has been achieved.

Maintenance Therapy for Opiate Cessation

50 mg daily following induction of therapy.

Alternatively, flexible dosing schedules have been suggested in an attempt to improve compliance. Administration of larger doses at longer intervals (e.g., 48–72 hours) may reduce opiate antagonist activity somewhat, but may improve compliance. Single doses >50 mg may increase risk of hepatic injury; weigh possible risks against probable benefits of flexible dosing.

Ingestion of the naltrexone dose generally should be observed in a clinic setting or by a responsible family member to ensure compliance, in which case, regimens requiring less frequent visits may be more acceptable to the patient.

Monitor patient compliance by random testing of urine for naltrexone and 6-β-naltrexol or for the presence of opiates.

Optimum duration of maintenance therapy not established; base on individual requirements and response.

In patients who discontinue naltrexone prematurely and then desire to resume therapy following a relapse to opiate abuse, perform urinalysis for the presence of opiates and, if necessary, a naloxone challenge test prior to resuming therapy. If there is evidence of opiate dependence, conduct detoxification prior to reinitiation of naltrexone therapy.

Opiate Detoxification† [off-label]

Various dosage regimens have been used for rapid or ultrarapid detoxification [off-label] of opiate dependence.

The following regimen of naltrexone, given in conjunction with clonidine to attenuate withdrawal manifestations, has been studied.

Day of Detoxification Therapy

Clonidine Hydrochloride

Naltrexone Hydrochloride

Day 1

0.005 mg/kg initially; then titrated according to the severity of withdrawal and the adverse effects induced by clonidine

Day 2

Administered every 4 hours to attenuate the withdrawal induced by naltrexone

Administered every 4 hours; 1 mg initially; then increased in 1-mg increments during the daytime on day 2

Day 3

Administered every 4 hours to attenuate the withdrawal induced by naltrexone; highest mean dosage was 2.3 mg daily on day 3

Administered every 4 hours; dosage increased in 2-mg increments during the daytime on day 3

Day 4

Administered only as needed to reduce signs and symptoms of withdrawal

10 mg 3 times daily

Day 5

Administered only as needed to reduce signs and symptoms of withdrawal

50 mg once daily

Alcohol Dependence

50 mg once daily, following verification that the patient is free of opiates. (See General under Dosage and Administration.)

Optimum duration of therapy not established; safety and efficacy established only in short-term (up to 12 weeks) studies.


380 mg every 4 weeks or once a month following verification that the patient is free of opiates. (See General under Dosage and Administration.)

If a dose is missed, reschedule administration with a health-care professional as soon as possible.

Therapy may be initiated with parenteral preparation; not necessary to initiate therapy with oral naltrexone and then switch to parenteral preparation.

Special Populations

Hepatic Impairment

Alcohol Dependence

Dosage adjustment not needed in patients with mild to moderate (Child-Pugh class A or B) hepatic impairment.

Renal Impairment

Alcohol Dependence

Dosage adjustment not needed in patients with mild renal impairment (Clcr of 50–80 mL/minute).

Cautions for Naltrexone




Hepatic Effects

Possible dose-related hepatocellular injury, manifested as increases in serum hepatic enzyme concentrations. (See Boxed Warning.)

Manufacturers state that naltrexone-induced hepatocellular injury appears to be a direct toxic rather than an idiosyncratic effect. Some clinicians suggest that liver function abnormalities may be caused by noroxymorphone, a minor metabolite of naltrexone that has opiate agonist activity.

Manufacturer of oral naltrexone recommends monitoring liver function at intervals deemed appropriate for the naltrexone dosage employed and the clinical status of the patient.

Local Reactions

IM injection associated with injection site reactions (e.g., tenderness, induration, pain, pruritus, ecchymosis, nodules, swelling) in most patients. Cellulitis, hematoma, abscess, sterile abscess, and necrosis also reported. Injection site reactions occur predominantly in females.

Some reactions may be very severe, result in substantial scarring, or require surgery, including debridement of necrotic tissue. Inadvertent sub-Q injection may increase likelihood of a severe injection reaction.

Patients should monitor the injection site and contact clinician if injection site reactions worsen or persist. (See Advice to Patients.) Promptly evaluate patients with signs of abscess, cellulitis, necrosis, or extensive swelling to determine if referral to a surgeon is warranted.

Verification of Opiate Abstinence Prior to Initiation of Therapy

Naltrexone may precipitate mild to severe withdrawal in patients physically dependent on opiates.

To minimize the risk of precipitating signs and symptoms of withdrawal, instruct opiate-dependent individuals who are candidates for naltrexone therapy to remain free of opiates for a minimum of 7–10 days prior to initiating therapy with the drug.

Absence of opiates in urine is frequently insufficient evidence that a patient is free of opiates. If it is uncertain whether the patient is opiate free, perform a naloxone challenge test prior to administering naltrexone. (See Naloxone Challenge Test under Dosage and Administration.)

Risks Associated with Self-administration of Opiates During Naltrexone Therapy

Self-administration of large doses of opiates in an attempt to overcome the antagonist activity of naltrexone may produce signs and symptoms of acute opiate overdosage (e.g., respiratory arrest, circulatory collapse, death).

Signs and symptoms of opiate overdosage also may occur following administration of smaller doses of opiate agonists relatively long after the last naltrexone dose or in an amount that results in a longer duration of agonist activity than the antagonist activity of naltrexone and its metabolites.

Advise patients of the serious consequences of self-administration of opiates during naltrexone therapy. (See Advice to Patients.)

Eosinophilic Pneumonia

Eosinophilic pneumonia reported rarely in patients receiving parenteral naltrexone. Consider eosinophilic pneumonia in patients with pneumonia who have not responded to anti-infective therapy.

General Precautions

Therapeutic Use of Opiates in Naltrexone-treated Patients

In an emergency situation when adequate analgesia can be achieved only by administration of an opiate agonist in naltrexone-treated patients, cautious administration of an opiate may afford adequate analgesia, but higher than usual dosages may be required. Whenever possible, use nonopiate analgesics, regional analgesia, conscious sedation with a benzodiazepine, or general anesthesia.

If an opiate is required as a component of anesthesia or analgesia, the patient should be continuously monitored in an anesthesia care setting by individuals who are trained in the use of anesthetic agents and in the management of respiratory depressant effects of potent opiates and who are not involved in the conduct of the surgical or diagnostic procedure.

Respiratory depression produced by the opiate may be deeper and more prolonged. Patients may experience apparent nonopiate receptor-induced effects such as facial swelling, pruritus, generalized erythema, or bronchoconstriction that are probably caused by opiate-induced histamine release and/or other mechanisms.

Use of a short-acting opiate with minimal respiratory depression is preferable; adjust dosage of the opiate agonist carefully according to individual requirements and response. Closely monitor the patient in a setting equipped and staffed by health-care personnel appropriately trained in CPR.

Discontinue oral naltrexone ≥48 hours prior to elective surgical procedures requiring opiate analgesia.

Avoid use of other opiate-agonist-containing preparations (e.g., those used for the management of cough or diarrhea) when alternative nonopiate therapy is available, since adequate therapeutic benefit may be difficult to achieve with an opiate.

Accidental Precipitation of Withdrawal

Accidental ingestion of naltrexone has precipitated severe withdrawal in some patients physically dependent on opiates; signs and symptoms of withdrawal usually appeared within 5 minutes of naltrexone ingestion and continued for up to 48 hours.


Increased risk of suicide in substance abusers with or without depression; risk is not abated by naltrexone therapy.

Individuals with Bleeding Disorders

Use IM preparation with caution in individuals with thrombocytopenia or a coagulation disorder (e.g., hemophilia).

Specific Populations


Category C.

Not known whether naltrexone affects the duration of labor and delivery.


Naltrexone and the active metabolite (6-β-naltrexol) are distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy not established in children <18 years of age.

Hepatic Impairment

Contraindicated in patients with acute hepatitis or hepatic failure. (See Boxed Warning and see Hepatic Effects under Cautions.)

Use with caution in patients with hepatic impairment. When administered orally, possible increased systemic exposure to the drug.

Renal Impairment

Use with caution in patients with moderate to severe renal impairment.

Common Adverse Effects

Treatment of opiate dependence: insomnia, anxiety, nervousness, abdominal pain and cramps, nausea, vomiting, fatigue, joint and muscle pain, headache.

Treatment of alcohol dependence: nausea, headache, dizziness, nervousness, fatigue, insomnia, vomiting, anxiety, somnolence, injection site reaction.

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test




Concomitant administration may reduce the duration of opiate withdrawal by decreasing opiate-induced postsynaptic supersensitivity


Both drugs are potentially hepatotoxic

Manufacturers recommend concomitant use only if the potential benefits justify the possible risks

Opiate agonists

Patients receiving naltrexone may not benefit therapeutically from opiate-containing preparations, including those used for the management of cough and cold, diarrhea, and pain

Naltrexone can precipitate potentially severe opiate withdrawal

Avoid use of opiate-containing preparations during naltrexone therapy when alternative nonopiate therapy is available

Avoid use of naltrexone in patients receiving opiates or in nondetoxified patients physically dependent on opiates

Phenothiazines (thioridazine)

Possible increased lethargy and somnolence

Tests, urinary opiates

Possible interference with some enzymatic assays for opiates

No interference reported with thin-layer (TLC), gas-liquid (GLC), or high-performance liquid (HPLC) chromatography assays for methadone or morphine

Tests, urinary quinine

No interference reported with TLC, GLC, or HPLC methods

Naltrexone Pharmacokinetics



Rapidly and almost completely (about 96%) absorbed following oral administration, but undergoes extensive first-pass metabolism in the liver; only 5–40% reaches systemic circulation unchanged.

Peak plasma concentrations of naltrexone and the active metabolite (6-β-naltrexol) usually occur within 1 hour following oral administration.

Following IM administration of the extended-release injection, naltrexone is released slowly and gradually from the microspheres by diffusion and erosion as the polylactide co-glycolide polymer degrades. Peak plasma concentrations of naltrexone and the active metabolite (6-β-naltrexol) occur in about 2–3 days; steady-state plasma concentrations of naltrexone and 6-β-naltrexol are attained by the end of the dosing interval after the first injection.

Following administration of a single IM dose of naltrexone 380 mg, total naltrexone exposure is three- to fourfold higher and 6-β-naltrexol exposure is 3.4-fold lower than exposure following oral administration of naltrexone 50 mg daily for 28 days.


Onset of opiate antagonism occurred 15–30 minutes following oral administration in a limited number of patients who had been receiving morphine chronically.

Decreases opiate craving within 3–5 weeks after start of oral naltrexone in individuals formerly dependent on opiates; reduction in opiate craving has occurred during the first week of therapy in some individuals, with further decreases occurring in subsequent weeks.


Duration of opiate antagonist activity appears to be dose dependent and is longer than that of equipotent doses of naloxone.

Special Populations

Changes in oral bioavailability appear to be related to severity of liver disease. AUC increased 5- or 10-fold in patients with compensated or decompensated cirrhosis, respectively.

Following IM administration, plasma concentrations of naltrexone and 6-β-naltrexol in individuals with mild to moderate hepatic impairment (Child-Pugh class A and B) are similar to those in healthy individuals with normal hepatic function.



Widely distributed throughout the body; considerable interindividual variation in distribution parameters during the first 24 hours following a single oral dose.

Not known whether naltrexone and/or its metabolites cross the placenta. Naltrexone and 6-β-naltrexol are distributed into human milk.

Plasma Protein Binding

Approximately 21–28%.



Metabolized in the liver principally by reduction of the 6-keto group of naltrexone to an active metabolite, 6-β-naltrexol (6-β-hydroxynaltrexone); other minor metabolites are formed.

Because oral but not IM administration of naltrexone results in substantial first-pass hepatic metabolism, 6-β-naltrexol concentrations following IM administration are substantially lower than concentrations achieved following oral administration.

Naltrexone and its metabolites may undergo enterohepatic circulation.

Elimination Route

Excreted principally in urine via glomerular filtration, mainly as metabolites (unconjugated and conjugated).


Following oral administration, biphasic.

Initial phase, oral administration: 1.1–3.9 hours for naltrexone; 2.3–3.1 hours for 6-β-naltrexol.

Terminal phase, oral administration: 9.7–10.3 hours for naltrexone; 11.4–16.8 hours for 6-β-naltrexol.

Following IM administration, half-life of naltrexone and 6-β-naltrexol is 5–10 days.

Special Populations

Following IM administration, pharmacokinetics not altered in patients with mild renal impairment (Clcr of 50–80 mL/minute).







Extended-release Injection

Store entire dose pack at 2–8°C. May be stored at temperatures not >25°C for ≤7 days prior to administration. Do not freeze.

After mixing with diluent, use immediately.


Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.



Dosage Forms


Brand Names



For injectable suspension, extended-release, for IM use

380 mg

Vivitrol (available as a dose pack containing naltrexone microspheres, diluent, needles)


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Naltrexone Hydrochloride


Dosage Forms


Brand Names




50 mg*

Naltrexone Hydrochloride

Tablets, film-coated

50 mg*

Naltrexone Hydrochloride

ReVia (scored)


AHFS DI Essentials™. © Copyright 2024, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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