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Naltrexone Hydrochloride

Pronunciation: nal-TREX-one HYE-droe-KLOR-ide
Class: Antidote

Trade Names

- Tablets, oral 50 mg

- Injection, powder for suspension, ER 380 mg


Opioid receptor antagonist markedly attenuating or completely blocking, reversibly, the subjective effects of IV-administered opioids.




Rapidly and nearly completely absorbed (96%) from the GI tract. T max is 1 h.


Transient initial peak within 2 h, followed by a second peak approximately 2 to 3 days later. About 14 days after dosing, concentrations decline slowly, with measurable levels for more than 1 mo. Exposure is 3- to 4-fold higher following IM administration compared with oral naltrexone.


Vd is estimated to be 1,350 L. Plasma protein binding is 21%.


More than 98% metabolized and extrahepatic sites may exist. The major metabolite is 6-beta-naltrexol. There are 2 minor metabolites. Less 6-beta-naltrexone is generated after IM administration compared with oral.


Renal Cl of naltrexone ranges from 30 to 127 mL/min, suggesting that renal elimination is primarily glomerular filtration. Urinary excretion of unchanged naltrexone is less than 2%, while urinary excretion of unchanged and conjugated 6-beta-naltrexol accounts for 43%. Naltrexone and its metabolites may undergo enterohepatic recirculation.

The elimination half-life is 5 to 10 days (IM) and 4 h (oral) for naltrexone, and 13 h (oral) for 6-beta-naltrexol.

Special Populations

Renal Function Impairment

Adequate studies of naltrexone in patients with moderate to severe renal impairment have not been conducted.

Hepatic Function Impairment

An increase in naltrexone AUC of approximately 5- and 10-fold in patients with compensated and decompensated liver cirrhosis, respectively, compared with subjects with healthy liver function has been reported. Adequate studies of naltrexone in patients with severe hepatic impairment have not been conducted.


Pharmacokinetics have not been evaluated in elderly patients.


Pharmacokinetics have not been evaluated in children.


In a study of healthy subjects (n = 18 women and 18 men), gender did not influence the pharmacokinetics of naltrexone.


The effect of race on the pharmacokinetics of naltrexone has not been studied.

Indications and Usage

Alcohol dependence; blockade of exogenously administered opioids (oral); prevention of relapse to opioid dependence following opioid detoxification (IM injection).

Unlabeled Uses

Postconcussional syndrome unresponsive to other treatments; irritable bowel syndrome; pathological gambling; pruritus.


Receiving opioid analgesics; currently dependent on opioids, including those maintained on opiate agonists (eg, LAAM [levo-alpha-acetyl-methadol], methadone); in acute opioid withdrawal; patients who have failed the naloxone challenge test or have positive urine screen for opioids; a history of sensitivity to naltrexone or any components of these products; acute hepatitis or liver failure.

Dosage and Administration


PO 50 mg once daily.

IM 380 mg every 4 wk or once a month.

Opioid Dependence

PO Start with 25 mg; if no withdrawal signs occur, patient may be started on 50 mg daily thereafter. Do not attempt treatment if patient has not remained opioid-free for at least 7 to 10 days or if signs of opioid withdrawal are observed following naloxone challenge.

IM 380 mg every 4 wk or once a month.

General Advice

  • Oral
  • Administer tablets without regard to meals, but administer with food if GI upset occurs.
  • A flexible approach to a dosing regimen may need to be employed in cases of supervised administration. Patients may receive naltrexone 50 mg every weekday with a 100 mg dose on Saturday, 100 mg every other day, or 150 mg every third day. The degree of blockade produced by naltrexone may be reduced by these extended dosing intervals. There may be a higher risk of hepatocellular injury with single doses above 50 mg, and use of higher doses and extended dosing intervals should balance the possible risks against the probable benefits.
  • If there is any question of occult opioid dependence, perform a naloxone challenge test. See manufacturer's prescribing information for administering the naloxone challenge test and interpreting the results.
  • Injection
  • IM injection must be prepared and administered by a health care provider.
  • Refer to the manufacturer's prescribing information for preparation techniques.
  • Administer IM injection as a gluteal injection, alternating buttocks, and use the carton components provided (eg, microspheres diluent, preparation needle, administration needle). Do not inject IV or subcutaneously.
  • If an IM dose is missed, give the next dose as soon as possible.
  • Properly mixed suspension will be milky white, will not contain clumps, and will move freely down the wall of the vial. Visually inspect for particulate matter and discoloration prior to administration.


Store tablets between 68° and 77°F. Store the injectable suspension in the refrigerator (36° to 46°F). Store unrefrigerated at temperatures not exceeding 77°F for no more than 7 days prior to administration. Do not freeze.

Drug Interactions


The safety and efficacy of concomitant use of naltrexone and disulfiram are unknown. The concomitant use of 2 potentially hepatotoxic medications is not ordinarily recommended unless the probable benefits outweigh the known risks.

Opioid analgesics

The effects of the opioid analgesic may be reduced or attenuated, precipitating a severe opioid withdrawal syndrome. Naltrexone administration is contraindicated in patients receiving opioid analgesics or dependent on opioids, including patients maintained on opiate agonists (eg, methadone).

Opioid-containing medication

Because of antagonistic effects of naltrexone, patients may not benefit from opioid medication. The amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged.


Lethargy and somnolence have been reported with coadministration of naltrexone. If an interaction is suspected, it may be necessary to discontinue naltrexone.

Laboratory Test Interactions

Naltrexone may be cross-reactive with certain immunoassay methods for detecting drugs of abuse, specifically opioids, in the urine.

Adverse Reactions


Hypertension (5%); changes in blood pressure, hot flushes, palpitations (postmarketing).


Headache (36%); asthenic conditions (23%); dizziness/syncope (16%); depression (15%); anxiety, sedation/somnolence (12%); insomnia, sleep disorder (14%); low energy, nervousness (more than 10%); feeling down, increased energy, irritability (less than 10%); fatigue (4%); suicide attempt/ideation (1%); abnormal thinking, agitation, confusion, euphoria, hallucinations, hyperkinesia, malaise, tremor (postmarketing).


Skin rash (12%); increased sweating (postmarketing).


Pharyngitis (17%); nasopharyngitis (7%); vision abnormalities (postmarketing).


Nausea (33%); dry mouth (24%); anorexia/decreased appetite/appetite disorder (20%); abdominal pain (16%); vomiting (14%); diarrhea (13%); abdominal cramps (more than 10%); constipation, increased thirst (less than 10%); toothache (4%).


Hepatotoxicity; elevations in liver enzymes or bilirubin, hepatic function abnormalities, hepatitis (postmarketing).

Lab Tests

Increased CPK (39%); increased ALT (13%); increased AST (10%); increased GGT (7%); decreased platelet count, increased eosinophil count.


Injection-site reaction (88%); tenderness (72%); induration (35%); other injection-site reactions, including nodules and swelling (32%); pain (17%); pruritus (10%); ecchymosis (7%).


Arthralgia/arthritis/joint stiffness (12%); joint and muscle pain (more than 10%); muscle cramps (8%); back pain/stiffness (7%); myalgia (postmarketing).


Eosinophilic pneumonia; dyspnea (postmarketing).


Chills, decreased potency, delayed ejaculation (less than 10%); influenza (5%); accidental opioid overdose, unintended precipitation of opioid withdrawal; chest pain, hypersensitivity, idiopathic thrombocytopenic purpura, retinal artery occlusion (postmarketing).




Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. Naltrexone is contraindicated in acute hepatitis or liver failure, and its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects. The margin of separation between the apparently safe dose of naltrexone and the dose causing hepatic injury appears to be only 5-fold or less. Patients should be warned of the risk of hepatic injury and advised to stop the use of naltrexone and seek medical attention if they experience symptoms of acute hepatitis.


Assess liver function (eg, alkaline phosphatase, bilirubin, transaminases) before starting therapy, and periodically thereafter based on clinical situation and dose of naltrexone. Monitor for the development of depression or suicidal thinking.


Category C .


Excreted in human milk.


Safety and efficacy not established.


Cases of urticaria, angioedema, and anaphylaxis have been observed.

Renal Function

Use with caution.

Hepatic Function

Contraindicated in acute hepatitis or liver failure; its use in patients with active liver disease must be carefully considered in light of its hepatotoxic effects.

Abstinence syndrome

To prevent occurrence of an acute abstinence syndrome, patient must be opioid-free for a minimum of 7 to 10 days.

Alcohol withdrawal

Use of naltrexone does not eliminate or diminish alcohol withdrawal symptoms.

Accidental precipitation of withdrawal

Severe opioid withdrawal syndromes precipitated by accidental ingestion of naltrexone may occur in opioid-dependent individuals. Withdrawal symptoms may appear within 5 min and last 48 h.

Eosinophilic pneumonia

May occur with IM use.

Hematological effects

Use IM naltrexone with caution in patients with thrombocytopenia or any coagulation disorder (eg, hemophilia, severe hepatic failure).

Naloxone challenge

Do not perform in patients showing clinical signs or symptoms of opioid withdrawal or in patients whose urine contains opioids.

Overcoming blockade

Any attempt by the patient to overcome the antagonism by taking opioids is dangerous and may lead to fatal overdose.

Rapid opioid withdrawal

Safe use has not been established.


Risk is not abated by naltrexone treatment.



IM injection

Abdominal pain, dizziness, nausea, somnolence.

Patient Information

  • Advise patients to read the Medication Guide before starting therapy and with each refill
  • Advise patient that medication will be most effective when taken exactly as prescribed and combined with participation in a community-based support group.
  • Advise patient that dose may be adjusted periodically in order to achieve max benefit.
  • Advise patient to take the tablets without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient to carry or wear medical identification (eg, card, bracelet) indicating naltrexone use.
  • Advise families and caregivers of patients being treated with naltrexone of the need to monitor patients for the emergence of symptoms of depression or suicidality and to report such symptoms to the patient's health care provider.
  • Advise patient that self-administration of small doses of heroin or any other opiate will not produce noticeable effects. Caution patient that self-administration of large doses of heroin or any other opiate may overcome the naltrexone blockade and can cause coma or death. Also, patients on naltrexone may not experience the same effects from opioid-containing analgesic, antidiarrheal, or antitussive medications.
  • Advise patient that drug may cause dizziness and to use caution while driving or performing other tasks requiring mental alertness and coordination until tolerance is determined.
  • Advise patient to stop taking and notify health care provider of any of the following: allergic reaction, stomach pain lasting more that a few days, white bowel movements, dark urine, yellowing of the eyes.
  • Advise patient who have previously used opioids that they may be more sensitive to lower doses of opioids after naltrexone treatment.
  • Advise patient that treatment of alcohol dependence is part of a program that includes counseling and support.
  • IM injection
  • Advise patient that Vivitrol may cause allergic pneumonia and to immediately notify health care provider if signs and symptoms of pneumonia (eg, coughing, shortness of breath, wheezing) develop.
  • Advise patient that nausea may be experienced following initial injection and that these episodes of nausea tend to be mild and subside within a few days.
  • Advise patients that a reaction at the site of naltrexone injection may occur. Reactions include pain, swelling, tenderness, induration, bruising, redness, and pruritus. Rarely, serious injection-site reactions may occur. Advise patients to seek medical attention for worsening skin reactions, particularly if the reaction does not improve 2 weeks following the injection. Promptly refer patients with worsening injection-site reactions to a surgeon.
  • Advise patients that because naltrexone is an IM injection and not an implanted device, once naltrexone is injected, it is not possible to remove it from the body.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.