Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Suspension Reconstituted, Intramuscular:
Vivitrol: 380 mg (1 ea)
Tablet, Oral, as hydrochloride:
Generic: 50 mg
Mechanism of Action
Naltrexone (a pure opioid antagonist) is a cyclopropyl derivative of oxymorphone similar in structure to naloxone and nalorphine (a morphine derivative); it acts as a competitive antagonist at opioid receptor sites, showing the highest affinity for mu receptors. Endogenous opioids are involved in modulating the expression of alcohol's reinforcing effects (Hemby 1997; Lee 2005). Naltrexone also modifies the hypothalamic-pituitary-adrenal axis to suppress alcohol consumption (Williams 2004).
Oral: Almost complete
Vd: ~1350 L; widely throughout the body but considerable interindividual variation exists
Extensively metabolized via noncytochrome-mediated dehydrogenase conversion to 6-beta-naltrexol (primary metabolite) and related minor metabolites; glucuronide conjugates are also formed from naltrexone and its metabolites
Oral: Extensive first-pass effect
Primarily urine (as metabolites and small amounts of unchanged drug)
Time to Peak
Serum: Oral: ~60 minutes; IM: Biphasic: ~2 hours (first peak), ~2 to 3 days (second peak)
Duration of Action
Oral: 50 mg: 24 hours; 100 mg: 48 hours; 150 mg: 72 hours; IM: 4 weeks
Oral: 4 hours; 6-beta-naltrexol: 13 hours; IM: naltrexone and 6-beta-naltrexol: 5 to 10 days (dependent upon erosion of polymer)
Use in Specific Populations
Special Populations: 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.
Use: Labeled Indications
Alcohol use disorder: Treatment of alcohol use disorder.
Opioid dependence: For the blockade of the effects of exogenously administered opioids.
Use: Off Label
Data from small controlled trials support the use of oral naltrexone in the management of cholestatic pruritus, with an onset of action as early as the first day in some patients.
American Association for the Study of Liver Diseases practice guidelines for primary biliary cirrhosis recommend the use of oral naltrexone for cholestatic pruritus refractory to treatment with bile acid sequestrants. The limiting factor to naltrexone use in the management of cholestatic pruritus is the possibility of an opioid withdrawal-like reaction, which may be avoided by starting the drug at a lower dose and titrating upward.
Pathological gambling disorderb
Data from 2 small controlled trials, in which naltrexone resulted in improvement on gambling assessment scales, suggest that it may be beneficial for the treatment of pathologic gambling disorder
Hypersensitivity to naltrexone or any component of the formulation; opioid dependence or current use of opioid analgesics (including partial opioid agonists); acute opioid withdrawal; failure to pass naloxone challenge or positive urine screen for opioids
Canadian labeling: Additional contraindications (not in the US labeling): Acute hepatitis; hepatic failure
Dosage and Administration
Note: Do not initiate therapy until patient is opioid-free (including tramadol) for at least 7 to 10 days as determined by urinalysis; consider naloxone challenge test to confirm patient is opioid-free if there is any suspicion since urinary opioid screen may not be sufficient proof.
Alcohol use disorder:
Oral: 50 mg daily; some patients may require doses up to 100 mg/day (APA [Reus 2018]). Alternative maintenance regimens may be used and include: 50 mg on weekdays with a 100 mg dose on Saturday; 100 mg every other day; or 150 mg every 3 days (degree of blockade may be reduced with extended dosing interval regimens and doses >50 mg may increase risk of hepatocellular injury).
IM: 380 mg once every 4 weeks
Oral: Initial: 25 mg; if no withdrawal signs occur, administer 50 mg/day thereafter; alternative maintenance regimens may be used and include: 50 mg on weekdays with a 100 mg dose on Saturday; 100 mg every other day; or 150 mg every 3 days (degree of blockade may be reduced with extended dosing interval regimens and doses >50 mg may increase risk of hepatocellular injury)
IM: 380 mg once every 4 weeks
Cholestatic pruritus (off-label use): Oral: Initial: 12.5 mg once daily; increase dose by 12.5 mg every 3 to 7 days until clinical benefits are achieved (AASLD [Lindor 2009]). Doses of 50 mg daily have been reportedly used for up to 28 weeks (Carson 1996; Terg 2002; Wolfhagen 1997).
Refer to adult dosing.
Injection: Prior to reconstitution, allow drug vial and provided diluent to reach room temperature (~45 minutes). Using the provided 1-inch preparation needle, reconstitute with 3.4 mL of the diluent and allow to dissolve by vigorously shaking the vial for ~1 minute. Mixed suspension will be milky white, free of clumps, and will move freely down the walls of the vial. Immediately after suspension, withdraw 4.2 mL of the suspension using the same preparation needle.
Prior to administration, replace the preparation needle with the appropriate size provided administration needle (use the 2-inch needle with the needle protection device for patients with a larger amount of subcutaneous tissue overlying the gluteal muscle; for very lean patients, the 1.5-inch needle may be appropriate; either needle may be used for patients with average body habitus). Prior to injection, remove any air bubbles and push on the plunger until 4 mL of the suspension remains in the syringe. Following reconstitution of the suspension, administer immediately.
Oral: May be administered with or without food. Administration with food or after meals may minimize adverse gastrointestinal effects. Advise patient not to self-administer opioids while receiving naltrexone therapy.
IM: Vivitrol: Administer IM into the upper outer quadrant of the gluteal area; must inject dose using one of the provided needles for administration. Use either the 1.5-inch needle (for very lean patients) or the 2-inch needle (for patients with a larger amount of subcutaneous tissue overlying the gluteal muscle). Either needle may be used for patients with average body habitus. Avoid inadvertent injection into a blood vessel; do not administer IV, SubQ, or into fatty tissue (the risk of serious injection site reaction is increased if given incorrectly as a SubQ injection or into fatty tissue instead of the gluteal muscle). Injection should alternate between the 2 buttocks. Do not substitute any components of the dose-pack.
Injection: Store unopened kit at 2°C to 8°C (36°F to 46°F). Kit may be kept at room temperature of ≤25°C (77°F) for ≤7 days prior to use; do not freeze. Following reconstitution of the suspension, administer immediately.
Tablet: Store at 20°C to 25°C (68°F to 77°F).
Bremelanotide: May decrease the serum concentration of Naltrexone. Avoid combination
Lofexidine: May decrease the serum concentration of Naltrexone. Monitor therapy
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Avoid combination
Opioid Agonists: Naltrexone may diminish the therapeutic effect of Opioid Agonists. Management: Seek therapeutic alternatives to opioids. See full drug interaction monograph for detailed recommendations. Consider therapy modification
Sibutramine: May enhance the adverse/toxic effect of Centrally Acting Weight Loss Agents. Avoid combination
May cause cross-reactivity with some opioid immunoassay methods.
Cardiovascular: Syncope (≤13%)
Central nervous system: Headache (25%), insomnia (≤14%), sleep disorder (≤14%), dizziness (≤13%), anxiety (12%)
Gastrointestinal: Nausea (33%), vomiting (14%), anorexia (≤14%), change in appetite (≤14%), decreased appetite (≤14%), diarrhea (13%), abdominal pain (11%)
Hepatic: Increased serum transaminases (20%), increased serum aspartate aminotransferase (2% to 14%)
Local: Injection site reaction (69%), tenderness at injection site (45%), induration at injection site (35%), pain at injection site (17%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (11% to 39%), asthenia (23%), arthralgia (≤12%), arthritis (≤12%), joint stiffness (≤12%)
Respiratory: Pharyngitis (11%)
1% to 10%:
Central nervous system: Depression (8% to 10%), drowsiness (≤4%), sedated state (≤4%), suicidal ideation (≤1%), suicidal tendencies (≤1%)
Dermatologic: Skin rash (6%)
Gastrointestinal: Xerostomia (5%)
Local: Itching at injection site (10%), bruising at injection site (7%)
Neuromuscular & skeletal: Muscle cramps (8%), back pain (≤6%), back stiffness (≤6%)
Frequency not defined:
Cardiovascular: Acute ischemic stroke, acute myocardial infarction, angina pectoris, atrial fibrillation, cardiac failure, cerebral aneurysm, chest pain, chest tightness, coronary arteriosclerosis, deep vein thrombosis, facial edema, palpitations, pulmonary embolism, unstable angina pectoris
Central nervous system: Abnormal dreams, agitation, alcohol withdrawal syndrome, chills, decreased mental acuity, delirium, disturbance in attention, euphoria, heat exhaustion, irritability, lethargy, migraine, paresthesia, peripheral pain, rigors, seizure
Dermatologic: Diaphoresis, night sweats, pruritus
Endocrine & metabolic: Decreased libido, dehydration, hot flash, hypercholesterolemia, weight gain, weight loss
Gastrointestinal: Abdominal discomfort, acute pancreatitis, cholecystitis, cholelithiasis, colitis, constipation, dysgeusia, flatulence, gastroenteritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, hemorrhoids, increased appetite, paralytic ileus
Genitourinary: Abscess of rectum and/or peri-rectal area, urinary tract infection
Hematologic & oncologic: Decreased platelet count, eosinophilia, leukocytosis, lymphadenopathy
Hepatic: Increased serum alanine aminotransferase
Hypersensitivity: Seasonal allergy
Infection: Tooth abscess
Neuromuscular & skeletal: Muscle spasm, myalgia
Ophthalmic: Blurred vision, conjunctivitis
Respiratory: Bronchitis, chronic obstructive pulmonary disease, dyspnea, laryngitis, nasal congestion, pharyngolaryngeal pain, pneumonia, sinusitis, upper respiratory tract infection
Postmarketing: Anaphylaxis, angioedema, eosinophilic pneumonitis, hepatic insufficiency, hepatitis, hypersensitivity reaction, opioid withdrawal syndrome, retinal artery occlusion, urticaria
Concerns related to adverse effects:
- Accidental opioid overdose: Patients who had been treated with naltrexone may respond to lower opioid doses than previously used. This could result in potentially life-threatening opioid intoxication. Patients should be aware that they may be more sensitive to lower doses of opioids after naltrexone treatment is discontinued, after a missed dose, or near the end of the dosing interval. Warn patients that any attempt to overcome opioid blockade during naltrexone therapy, could potentially lead to fatal opioid overdose; the opioid competitive receptor blockade produced by naltrexone is potentially surmountable in the presence of large amounts of opioids.
- Acute opioid withdrawal: May precipitate symptoms of acute withdrawal in opioid-dependent patients, including pain, hypertension, sweating, agitation, and irritability; in neonates: shrill cry, failure to feed.
- Eosinophilic pneumonia: Cases of eosinophilic pneumonia have been reported and should be considered in patients presenting with progressive hypoxia and dyspnea.
- Hepatocellular injury: Dose-related hepatocellular injury is possible; the margin of separation between the apparent safe and hepatotoxic doses appears to be ≤5-fold. Discontinue therapy if signs/symptoms of acute hepatitis develop. Clinicians should note that elevated transaminases may be a result of pre-existing alcoholic liver disease, hepatitis B and/or C infection, or concomitant use of other hepatotoxic drugs; abrupt opioid withdrawal may also lead to acute liver injury.
- Hypersensitivity reactions: Hypersensitivity, including urticaria, angioedema, and anaphylaxis, have been reported.
- Injection site reactions: Serious injection site reactions (eg, cellulitis, induration, hematoma, abscess, necrosis) have been reported with use, including severe cases requiring surgical debridement. Females appear to be at a higher risk. Patients should report any injection site pain, swelling, bruising, pruritus, or redness that does not improve (or worsens). For IM use only in the gluteal muscle, do not administer IV, SubQ, or into fatty tissue; incorrect administration may increase the risk of injection site reactions.
- Suicidal thoughts/depression: Suicidal thoughts, attempted suicide, and depression have been reported postmarketing; monitor closely.
- Bleeding disorders: Use IM injection with caution in patients thrombocytopenia or any bleeding disorder (including hemophilia and severe hepatic failure), or patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration.
- Hepatic impairment: Use is not recommended in acute hepatitis or hepatic failure (APA [Reus 2018]).
- Renal impairment: Use with caution in patients with moderate to severe renal impairment (has not been studied).
Dosage form specific issues:
- Injection: Vehicle used in the injectable naltrexone formulation (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis following injection of other drug products that also use the polylactide-co-glycolide microspheres vehicle.
- Detoxified opioid addiction: Patients should be opioid-free (including tramadol) for a minimum of 7 to 10 days; a naloxone challenge test may be helpful to confirm patient is opioid-free prior to therapy if there is any suspicion since urinary opioid screen may not be sufficient proof. Patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks. Use of naltrexone does not eliminate or diminish withdrawal symptoms.
- Emergency pain management: In naltrexone-treated patients requiring emergency pain management, consider alternatives to opioid therapy (eg, regional analgesia, nonopioid analgesics, general anesthesia). If opioid therapy is required for pain therapy, patients should be under the direct care of a trained anesthesia provider.
- Surgery: In patients treated with naltrexone for opioid addiction who requiring surgery, discontinue oral naltrexone at least 72 hours before scheduled elective surgery if opioid use is anticipated; extended-release IM naltrexone should be discontinued at least 30 days prior to scheduled surgery (oral naltrexone may be used temporarily) (Kampman [ASAM 2015]).
Liver function tests (baseline and periodic); monitor for opioid withdrawal, injection site reactions with IM administration, and depression and/or suicidal thinking
Naltrexone and the 6-beta-naltrexol metabolite cross the placenta (Towers 2020).
Alcohol use and opioid use disorder are associated with adverse fetal and obstetrical outcomes. Information related to the use of naltrexone during pregnancy is limited (ACOG 711 2017; Farid 2008; Towers 2020; Tran 2017).
Clinical practice guidelines recommend that if a woman being treated with naltrexone for the treatment of opioid use disorder becomes pregnant, naltrexone should be discontinued if the patient and physician agree that the risk of relapse if low. If patient is concerned about relapse and wishes to continue naltrexone, the patient should be informed of the potential risks of continuing treatment and consent for ongoing treatment should be obtained. If naltrexone is discontinued and the patient subsequently relapses, consideration should be given for treatment with methadone or buprenorphine (Kampman [ASAM 2015]). Pharmacological agents should not be used for the treatment of alcohol use disorder in pregnant women unless needed for the treatment of acute alcohol withdrawal or a coexisting disorder; agents other than naltrexone are recommended for acute alcohol withdrawal (APA [Reus 2018]).
Pregnancy testing is recommended prior to initiating naltrexone therapy for opioid use disorder (SAMHSA 2018).
What is this drug used for?
- It is used to help keep you alcohol-free.
- It is used to keep a drug-free state.
- It may be given for other reasons.
Frequently reported side effects of this drug
- Abdominal pain
- Muscle cramps
- Trouble sleeping
- Joint pain
- Muscle pain
- Lack of appetite
- Loss of strength and energy
- Common cold symptoms
- Tooth pain
- Dry mouth
- Increased thirst
- Nose irritation
- Throat irritation
- Back pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin
- Depression like thoughts of suicide, anxiety, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion
- Severe dizziness
- Passing out
- Severe headache
- Vision changes
- Sexual dysfunction (males)
- Trouble breathing
- Slow breathing
- Shallow breathing
- Severe pulmonary disorder like lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse
- Severe injection site blisters, scabs, pain, edema, lumps, or irritation
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.