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Naltrexone: Drug information

Naltrexone: Drug information
(For additional information see "Naltrexone: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Vivitrol
Brand Names: Canada
  • APO-Naltrexone;
  • ReVia
Pharmacologic Category
  • Antidote;
  • Opioid Antagonist
Dosing: Adult

Dosage guidance:

Clinical considerations: Do not initiate therapy until patient has passed a naloxone challenge test or is opioid-free (including tramadol) for at least 7 to 10 days after last opioid use; up to 14 days may be necessary for patients on long-acting opioids (eg, methadone, buprenorphine) (Ref). If need for opioid pain management is anticipated during treatment (eg, for elective surgery), discontinue oral naltrexone ≥3 days prior to surgery or IM naltrexone ≥30 days prior to surgery (Ref).

Alcohol use disorder, moderate to severe

Alcohol use disorder, moderate to severe:

Note: Not recommended for patients currently taking opioids or with acute hepatitis, liver enzymes ≥3 to 5 times normal, or liver failure (Ref). May be initiated while the patient is actively drinking (Ref). Some experts consider alternative therapy if goals are not met within 6 months of treatment (Ref).

Oral: 50 mg once daily; may increase to 100 mg once daily after 1 week based on response and tolerability. Some experts initiate with 25 mg once daily for several days before increasing to 50 mg once daily (Ref).

IM: 380 mg once every 4 weeks.

Opioid use disorder, mild to severe

Opioid use disorder, mild to severe (alternative agent for moderate to severe):

Note: Treatment initiation should be medically supervised due to risk for precipitated withdrawal. Some experts consider switching to alternative therapy if goals are not met within 3 to 6 months of treatment (Ref).

Oral (alternative route): Initial: 25 mg once daily for 1 to 3 days; if no withdrawal signs occur, administer 50 mg once daily thereafter. Note: Use only for patients who are highly motivated or able to comply with techniques such as observed dosing to enhance adherence; efficacy is limited when patient adherence is poor (Ref).

IM: 380 mg once every 4 weeks. Note: Patients who experience a reduction in efficacy prior to 4 weeks (eg, breakthrough cravings, ability to overcome opioid receptor blockade), may benefit from dosing every 3 weeks; however, no clinical trials have evaluated dosing frequencies <4 weeks (Ref).

Switching from buprenorphine to naltrexone: Taper the buprenorphine dose gradually and discontinue. Wait 7 to 14 days before initiating treatment with naltrexone. A naloxone challenge may be used to demonstrate an absence of physical dependence (Ref).

Switching from methadone to naltrexone: Taper the methadone dose gradually and discontinue. Wait 7 to 14 days before initiating treatment with naltrexone. A naloxone challenge may be used to demonstrate an absence of physical dependence (Ref).

Switching from naltrexone to methadone or buprenorphine: Begin methadone or buprenorphine ~1 day following last dose of oral naltrexone and ~28 days following last dose of IM naltrexone (Ref).

Pruritus

Pruritus (off-label use):

Opioid-induced, associated with neuraxial opioid administration:

Oral: 6 mg once; generally, doses >6 mg may reverse analgesia (Ref).

Nonopioid-induced (eg, from cholestasis) (alternative agent): Note: Studies of naltrexone for uremic pruritus have mixed results (Ref).

Oral: 12.5 mg to 50 mg once daily (Ref).

Dosing: Kidney Impairment: Adult

Mild impairment: No dosage adjustment necessary.

Moderate-to-severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied); use with caution since naltrexone and its primary metabolite are primarily excreted in urine.

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: No dosage adjustment provided in manufacturer’s labeling (has not been studied); naltrexone AUC increased ~5- and 10-fold in patients with compensated or decompensated hepatic cirrhosis respectively. Use is not recommended in acute hepatitis or hepatic failure (Ref).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions (Significant): Considerations
Accidental opioid overdose

Naltrexone may result in accidental opioid overdose in patients with opioid dependence or opioid use disorder. Risk of opioid overdose with naltrexone use may be higher than other opioid agonist treatments (Ref). Opioid overdose related to naltrexone use may result in life-threatening and fatal events (Ref).

Mechanism: Related to the pharmacologic action; naltrexone is an opioid receptor-antagonist, reducing or blocking the effects of opioids and potentially leading to secondary up-regulation of opioid receptors. Patients may be hypersensitive to opioid effects and susceptible to overdose at lower opioid doses than previously tolerated (Ref). In addition, the opioid competitive receptor blockade produced by naltrexone is potentially surmountable in the presence of large amounts of opioids.

Onset: Varied; overdose occurred within 2 weeks after discontinuation in one study (Ref). In another study, overdose occurred within a 12-month period (Ref).

Risk factors:

• Naltrexone discontinuation

• Missed doses of naltrexone

• Near the end of the naltrexone dosing interval

• Opioid dose (Ref)

• Time since opioid administration (Ref)

• Patient metabolism (Ref)

Hepatotoxicity

Naltrexone may cause transient, mildly increased serum transaminases (Ref). Most increases in serum transaminases resolve (some with continued therapy) (Ref). Hepatitis has been reported.

Mechanism: Dose-related; exact mechanism unknown. (Ref).

Onset: Varied; most increased serum alanine aminotransferase and increased serum aspartate aminotransferase occur in the first 30 days of therapy, but may occur later (Ref).

Risk factors:

• Higher oral doses (Ref)

• Concurrent NSAIDs (Ref)

• Older patients (>50 years) (Ref)

Injection site reactions

Naltrexone IM administration may cause injection site reaction, pain at injection site, tenderness at injection site, bruising at injection site, swelling at injection site, injection site nodule, and itching at injection site. Serious reactions, including abscess at injection site, cellulitis at injection site, hematoma at injection site, induration at injection site, sterile abscess at injection site, and tissue necrosis at injection site have been reported; some requiring surgical intervention (Ref). Nicolau syndrome or embolia cutis medicamentosa has been reported, characterized by blanching and pain around the injection site, followed by erythema and tissue necrosis (Ref).

Mechanism: Most injection site reactions may be related to improper administration. Nicolau syndrome may occur due to direct damage to the end artery or cytotoxic effects of naltrexone and/or additives in the preparation (Ref).

Onset: Varied; most injection site reactions occur within 1 to 3 days but may occur more than 10 days after injection (Ref). Nicolau syndrome may occur after 1 week (Ref).

Risk factors:

• Improper administration (eg, inadvertent SUBQ administration) (Ref)

• Patients with HIV (Ref)

Naltrexone-precipitated opioid withdrawal

Naltrexone may precipitate opioid withdrawal syndrome in patients with opioid dependence or opioid use disorder. Symptoms may be severe and include abdominal pain, agitation, altered level of consciousness, confusion, diaphoresis, diarrhea, dilated pupils, dizziness, irritability, nausea, pain, tachycardia, and vomiting (Ref). Naltrexone-precipitated opioid withdrawal symptoms may last 48 to 72 hours (Ref). Withdrawal symptoms may require hospitalization but are rarely life-threatening (Ref).

Mechanism: Related to the pharmacologic action; naltrexone displaces opioids from opioid receptors, precipitating withdrawal (Ref).

Onset: Rapid; within 5 minutes, peaking between 1 to 3 hours (Ref).

Risk Factors:

• Dose and timing of opioid use (Ref)

• Naltrexone administration prior to adequate opioid-free period

• Accidental or deliberate naltrexone administration (Ref)

• Transitioning from methadone or buprenorphine to naltrexone

• Peri-operative pain management (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions are as reported with the IM formulation.

>10%:

Cardiovascular: Syncope (≤13%)

Gastrointestinal: Abdominal pain (11%), anorexia (≤14%), change in appetite (≤14%), decreased appetite (≤14%), diarrhea (13%), nausea (33%), vomiting (14%)

Hepatic: Increased serum aspartate aminotransferase (2% to 14%) (table 1), increased serum transaminases (20%) (table 2)

Naltrexone: Adverse Reaction: Increased Serum Aspartate Aminotransferase

Drug (Naltrexone)

Placebo

Dosage Form

Indication

14%

11%

IM

Opioid dependence

2%

0.9%

IM

Alcohol dependence

Naltrexone: Adverse Reaction: Increased Serum Transaminases

Drug (Naltrexone)

Placebo

Dosage Form

Indication

20%

13%

IM

Opioid dependence

Local: Induration at injection site (35%) (table 3), injection-site reaction (69%, including injection-site nodule and swelling at injection site) (table 4), pain at injection site (17%) (table 5), tenderness at injection site (45%) (table 6)

Naltrexone: Adverse Reaction: Induration at Injection Site

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

35%

8%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Naltrexone: Adverse Reaction: Injection Site Reaction

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

69%

50%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Naltrexone: Adverse Reaction: Pain at Injection Site

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

17%

7%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Naltrexone: Adverse Reaction: Tenderness at Injection Site

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

45%

39%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Nervous system: Anxiety (12%), asthenia (23%), dizziness (≤13%), headache (25%), insomnia (≤14%), sleep disorder (≤14%)

Neuromuscular & skeletal: Arthralgia (≤12%), arthritis (≤12%), increased creatine phosphokinase in blood specimen (11% to 39%), joint stiffness (≤12%)

Respiratory: Pharyngitis (11%)

1% to 10%:

Dermatologic: Skin rash (6%)

Gastrointestinal: Xerostomia (5%)

Local: Bruising at injection site (7%) (table 7), injection-site pruritus (10%) (table 8)

Naltrexone: Adverse Reaction: Bruising at Injection Site

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

7%

5%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Naltrexone: Adverse Reaction: Injection-Site Pruritus

Drug (Naltrexone)

Placebo

Dose

Dosage Form

Indication

Number of Patients (Naltrexone)

Number of Patients (Placebo)

10%

0%

380 mg every 4 weeks

IM

Alcohol dependence

205

214

Nervous system: Depression (8% to 10%), drowsiness (≤4%), sedated state (≤4%), suicidal ideation (≤1%), suicidal tendencies (≤1%)

Neuromuscular & skeletal: Back pain (≤6%), back stiffness (≤6%), muscle cramps (8%)

Frequency not defined:

Cardiovascular: , Angina pectoris, atrial fibrillation, chest pain, chest tightness, coronary artery disease, deep vein thrombosis, heart failure, palpitations, pulmonary embolism

Dermatologic: Diaphoresis, night sweats, pruritus

Endocrine & metabolic: Decreased libido, dehydration, heat exhaustion, hot flash, hypercholesterolemia, weight gain, weight loss

Gastrointestinal: Abdominal distress, cholecystitis, cholelithiasis, colitis, constipation, dysgeusia, flatulence, gastroenteritis, gastroesophageal reflux disease, gastrointestinal hemorrhage, hemorrhoids, increased appetite, paralytic ileus

Hematologic & oncologic: Decreased platelet count, eosinophilia, leukocytosis, lymphadenopathy

Hypersensitivity: Facial edema

Nervous system: Abnormal dreams, acute ischemic stroke, agitation, alcohol withdrawal syndrome, cerebral aneurysm, chills, decreased mental acuity, disturbance in attention, euphoria, irritability, lethargy, migraine, paresthesia, rigors, seizure

Neuromuscular & skeletal: Limb pain, muscle spasm, myalgia

Ophthalmic: Blurred vision, conjunctivitis

Respiratory: Bronchitis, chronic obstructive pulmonary disease, dyspnea, laryngitis, nasal congestion, pharyngolaryngeal pain, sinusitis

Miscellaneous: Fever

Postmarketing:

Cardiovascular: Acute myocardial infarction (Gubitosa 2020)

Dermatologic: Urticaria

Gastrointestinal: Acute pancreatitis (Verma 2016)

Hepatic: Hepatitis, increased serum alanine aminotransferase (Sax 1994)

Hypersensitivity: Anaphylaxis, angioedema

Local: Abscess at injection site, cellulitis at injection site, hematoma at injection site, sterile abscess at injection site, tissue necrosis at injection site

Nervous system: Delirium (Gowing 2017), opioid withdrawal syndrome (Hassanian-Moghaddam 2014; Yeo 2003)

Respiratory: Eosinophilic pneumonitis (Gastfriend 2011), pneumonia (including interstitial pneumonia) (Gastfriend 2011)

Contraindications

Hypersensitivity to naltrexone or any component of the formulation; current physiological 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

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Canadian labeling: Additional contraindications (not in the US labeling): Acute hepatitis; hepatic failure

Warnings/Precautions

Concerns related to adverse effects:

• Suicidal thoughts/depression: Suicidal thoughts, attempted suicide, and depression have been reported postmarketing; monitor closely.

Disease-related concerns:

• 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.

Other warnings/precautions:

• Discontinuation of therapy: There is no maximum recommended duration for maintenance treatment of opioid use disorder; patients may require treatment indefinitely. Advise patients of the potential to relapse to illicit drug use following discontinuation of opioid use disorder treatment (SAMHSA 2021).

• Opioid use disorder: 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. Oral naltrexone tablets have not been shown to be more effective than placebo for opioid use disorder due to poor patient adherence (SAMHSA 2021).

• 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.

• Naloxone access: Discuss the availability of naloxone with all patients, as well as their caregivers, at initial treatment and regularly during therapy (eg, with each subsequent naltrexone injection). Patients being treated for an opioid use disorder have the potential for relapse and are at risk for opioid overdose; this risk may be increased in patients treated with naltrexone near the end of the naltrexone dosing interval (particularly if using naltrexone injection), if a dose of naltrexone is missed, or when naltrexone treatment is discontinued. Inform patients and caregivers on options for obtaining naloxone (eg, by prescription, directly from a pharmacist, a community-based program) as permitted by state dispensing and prescribing guidelines. Educate patients and caregivers on how to recognize respiratory depression, proper administration of naloxone, and getting emergency help.

• Surgery: In patients treated with naltrexone for opioid use disorder who are 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) (ASAM 2020).

Dosage Forms: US

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

Generic Equivalent Available: US

May be product dependent

Pricing: US

Suspension (reconstituted) (Vivitrol Intramuscular)

380 mg (per each): $1,969.33

Tablets (Naltrexone HCl Oral)

50 mg (per each): $2.14 - $4.28

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

ReVia: 50 mg

Generic: 50 mg

Administration: Adult

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 deep IM into the gluteal muscle; 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.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Vivitrol: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/021897s052lbl.pdf#page=33

Use: Labeled Indications

Alcohol use disorder: Treatment of alcohol use disorder.

Opioid use disorder, mild to severe: For the blockade of the effects of exogenously administered opioids.

Limitation of use: Oral naltrexone tablets have not been shown to be more effective than placebo for opioid use disorder due to poor patient adherence (SAMHSA 2021).

Use: Off-Label: Adult

Pruritus

Medication Safety Issues
Sound-alike/look-alike issues:

Naltrexone may be confused with methylnaltrexone, naloxone

ReVia may be confused with Revatio

Administration issues:

Vivitrol: For deep intramuscular (IM) gluteal injection only

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Bremelanotide: May decrease the serum concentration of Naltrexone. Risk X: Avoid combination

Lofexidine: May decrease the serum concentration of Naltrexone. Risk C: Monitor therapy

Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine. Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination

Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the risk for opioid withdrawal may be increased. Risk X: 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. Risk X: Avoid combination

Sibutramine: May enhance the adverse/toxic effect of Centrally Acting Weight Loss Agents. Risk X: Avoid combination

Reproductive Considerations

Naltrexone is not the preferred treatment for opioid use disorder during pregnancy; pregnancy testing is recommended prior to initiating naltrexone therapy (SAMHSA 2021).

Pregnancy Considerations

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).

Information related to the use of naltrexone for the treatment of opioid use disorder during pregnancy is limited. Consider transitioning to a preferred agent or discontinue treatment if the patient and health care provider agree the risk of relapse is low. If treatment with naltrexone continues, the risks and benefits should be discussed (ASAM 2020; SAMHSA 2021). Pregnant patients are not appropriate candidates for the ER injection (SAMHSA 2021).

Pharmacological agents should not be used for the treatment of alcohol use disorder in pregnant patients 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]).

Breastfeeding Considerations

Naltrexone and the 6-beta-naltrexol metabolite are present in breast milk (Chan 2004).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Pharmacological agents should not be used for the treatment of alcohol use disorder in breastfeeding patients 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]).

Monitoring Parameters

Liver function tests (baseline and periodic); signs or symptoms of opioid withdrawal, injection-site reactions with IM administration; pregnancy test (baseline); hepatitis and HIV testing, particularly for patients with opioid use disorder (prior to initiation) (SAMHSA 2021); and depression and/or suicidal thinking

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).

Pharmacokinetics (Adult Data Unless Noted)

Duration: Oral: 50 mg: 24 hours; 100 mg: 48 hours; 150 mg: 72 hours; IM: 4 weeks

Absorption: Oral: Almost complete

Distribution: Vd: ~1350 L; widely throughout the body but considerable interindividual variation exists

Metabolism: 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

Protein binding: 21%

Bioavailability: Oral: Variable range (5% to 40%)

Half-life elimination: Oral: 4 hours; 6-beta-naltrexol: 13 hours; IM: Naltrexone and 6-beta-naltrexol: 5 to 10 days (dependent upon erosion of polymer)

Time to peak, serum: Oral: ~60 minutes; IM: Biphasic: ~2 hours (first peak), ~2 to 3 days (second peak)

Excretion: Primarily urine (as metabolites and small amounts of unchanged drug)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AR) Argentina: Nalcotrex | Revez;
  • (AT) Austria: Dependex | Ethylex | Naltrexin | Naltrexon accord | Naltrexon hexal pharma | Nemexin | Revia;
  • (AU) Australia: Apo naltrexone | Naltrexone QP | Revia;
  • (BD) Bangladesh: Naltrax | Nodict;
  • (BE) Belgium: Nalorex | Naltrexone accord;
  • (BG) Bulgaria: Adepend | Revia;
  • (BR) Brazil: Revia | Uninaltrex;
  • (CH) Switzerland: Nemexin;
  • (CL) Chile: Nalerona;
  • (CN) China: Naltrexone | Narcoral | Nuo xin sheng;
  • (CZ) Czech Republic: Adepend | Naltrexone aop | Revia;
  • (DE) Germany: Adepend | Nalorex | Naltrexon HCl aop | Naltrexonhydrochlorid accord | Nemexin;
  • (DO) Dominican Republic: Naltima;
  • (EE) Estonia: Naltrexone accord | Naltrexone aop | Nodict | Revia;
  • (EG) Egypt: Anarcol | Deltrexone | Nerquon | Revia | Trexone;
  • (ES) Spain: Celupan | Naltrexona accord | Revia | Tranalex;
  • (FI) Finland: Naltrexon vitaflo | Naltrexone accord | Naltrexone POA Pharma | Revia;
  • (FR) France: Nalorex | Naltrexone Intas | Naltrexone Serb | Revia;
  • (GB) United Kingdom: Adepend | Nalorex | Naltrexone accord | Naltrexone aop | Opizone;
  • (GR) Greece: Nalorex;
  • (HK) Hong Kong: Naltrexone HCl L. Molteni | Revia | Trexan;
  • (HU) Hungary: Adepend | Nemexin | Revia;
  • (ID) Indonesia: Nutrexon | Phaltrexia | Revia;
  • (IE) Ireland: Ethylex | Nalorex | Naltrexone | Revia;
  • (IL) Israel: Revia;
  • (IN) India: Addtrex | Nalcon | Naltima | Naltivive | Naltox | Nodict;
  • (IT) Italy: Nalorex | Naltrexone Accord Healthcare | Narcoral;
  • (JO) Jordan: Revia;
  • (KE) Kenya: Addtrex;
  • (KR) Korea, Republic of: Hulexone | I rexone | Mislim | Naltra | Naltrexin | Naltrexone | Narex | Pharma naltrexone | Revia | Traxone | Wi naltrexone;
  • (LB) Lebanon: Revia;
  • (LT) Lithuania: Adepend | Nalorex | Naltrexone | Naltrexone accord | Revia;
  • (LV) Latvia: Naltrexone | Naltrexone accord | Revia;
  • (MX) Mexico: Arrop | Revia;
  • (MY) Malaysia: Naltrexone | Narpan | Revia | Trexan;
  • (NG) Nigeria: Lodonal;
  • (NL) Netherlands: Nalorex | Naltrexon | Naltrexon hydrochloride accord | Naltrexonhydrochloride pch | Revia;
  • (NO) Norway: Adepend | Nalorex | Naltrexon | Naltrexon accord | Naltrexone accord | Naltrexone poa | Revia;
  • (NZ) New Zealand: Naltraccord | Revia;
  • (PE) Peru: Nalerona;
  • (PK) Pakistan: Trexan | Zalter;
  • (PL) Poland: Adepend | Nalorex | Naltex | Naltrexone hydrochloride Accord | Nemexin | Revia | Vivitrol;
  • (PR) Puerto Rico: Naltrexone HCL | Revia;
  • (PT) Portugal: Basinal | Destoxican | Nalorex | Naltrexona accord | Naltrexona wynn;
  • (PY) Paraguay: Nalerona;
  • (QA) Qatar: Adepend;
  • (RO) Romania: Revia;
  • (RU) Russian Federation: Naltrexone | Revia | Vivitrol;
  • (SE) Sweden: Naltrexon | Naltrexon abcur | Naltrexone accord | Naltrexone POA Pharma | Revia;
  • (SG) Singapore: Narpan | Revia | Trexan;
  • (SI) Slovenia: Adepend | Revia;
  • (SK) Slovakia: Adepend;
  • (TH) Thailand: Revia;
  • (TR) Turkey: Ethylex;
  • (TW) Taiwan: Revia;
  • (UA) Ukraine: Naltima | Naltrex | Naltrexin;
  • (UY) Uruguay: Regental | Servixone;
  • (VE) Venezuela, Bolivarian Republic of: Naltrexin | Naltrexone;
  • (ZA) South Africa: Naltima | Revia
  1. Abboud TK, Afrasiabi A, Davidson J, et al. Prophylactic oral naltrexone with epidural morphine: effect on adverse reactions and ventilatory responses to carbon dioxide. Anesthesiology. 1990a;72(2):233-237 [PubMed 2105673]
  2. Abboud TK, Lee K, Zhu J, et al. Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. Anesth Analg. 1990b;71(4):367-370. doi:10.1213/00000539-199010000-00008 [PubMed 2205128]
  3. Ahamad K, Korthuis PT, Lum PJ, Johnson C, Wood E. A delayed injection-site reaction in a patient receiving extended-release naltrexone. Subst Abus. 2016;37(2):278-280. doi:10.1080/08897077.2016.1138919 [PubMed 26820699]
  4. American College of Obstetricians and Gynecologists (ACOG) Committee on Obstetric Practice. Committee opinion No. 711: opioid use and opioid use disorder in pregnancy. Obstet Gynecol. 2017;130(2):e81-e94. doi:10.1097/AOG.0000000000002235. [PubMed 28742676]
  5. American Society of Addiction Medicine (ASAM). The ASAM national practice guideline for the treatment of opioid use disorder: 2020 focused update. J Addict Med. 2020;14(2S)(suppl 1):1‐91. doi:10.1097/ADM.0000000000000633 [PubMed 32511106]
  6. Anton RF, O'Malley SS, Ciraulo DA, et al; COMBINE Study Research Group. Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial. JAMA. 2006;295(17):2003-2017. doi:10.1001/jama.295.17.2003 [PubMed 16670409]
  7. Carson KL, Tran TT, Cotton P, Sharara AI, Hunt CM. Pilot study of the use of naltrexone to treat the severe pruritus of cholestatic liver disease. Am J Gastroenterol. 1996;91(5):1022-1023. [PubMed 8633543]
  8. Chan CF, Page-Sharp M, Kristensen JH, O'Neil G, Ilett KF. Transfer of naltrexone and its metabolite 6,beta-naltrexol into human milk. J Hum Lact. 2004;20(3):322-326. doi:10.1177/0890334404266881. [PubMed 15296587]
  9. Croop RS, Faulkner EB, Labriola DF. The safety profile of naltrexone in the treatment of alcoholism. Results from a multicenter usage study. The Naltrexone Usage Study Group. Arch Gen Psychiatry. 1997;54(12):1130-1135. doi:10.1001/archpsyc.1997.01830240090013 [PubMed 9400350]
  10. Curatolo C, Trinh M. Challenges in the perioperative management of the patient receiving extended-release naltrexone. A A Case Rep. 2014;3(11):142-144. doi:10.1213/XAA.0000000000000069 [PubMed 25612099]
  11. Digiusto E, Shakeshaft A, Ritter A, O'Brien S, Mattick RP; NEPOD Research Group. Serious adverse events in the Australian National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD) [published correction appears in Addiction. 2005;100(1):139]. Addiction. 2004;99(4):450-460. doi:10.1111/j.1360-0443.2004.00654.x [PubMed 15049745]
  12. Farid WO, Dunlop SA, Tait RJ, Hulse GK. The effects of maternally administered methadone, buprenorphine and naltrexone on offspring: review of human and animal data. Curr Neuropharmacol. 2008;6(2):125-150. doi:10.2174/157015908784533842. [PubMed 19305793]
  13. Fishman M. Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone. Addiction. 2008;103(8):1399-1401. doi:10.1111/j.1360-0443.2008.02252.x [PubMed 18855831]
  14. Garbutt JC, Kranzler HR, O'Malley SS, et al; Vivitrex Study Group. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a randomized controlled trial. JAMA. 2005;293(13):1617-1625. doi:10.1001/jama.293.13.1617 [PubMed 15811981]
  15. Gastfriend DR. Intramuscular extended-release naltrexone: current evidence. Ann N Y Acad Sci. 2011;1216:144-166. doi:10.1111/j.1749-6632.2010.05900.x [PubMed 21272018]
  16. Gibson AE, Degenhardt LJ. Mortality related to pharmacotherapies for opioid dependence: a comparative analysis of coronial records. Drug Alcohol Rev. 2007;26(4):405-410. doi:10.1080/09595230701373834 [PubMed 17564876]
  17. Gowing L, Ali R, White JM. Opioid antagonists with minimal sedation for opioid withdrawal. Cochrane Database Syst Rev. 2017;5(5):CD002021. doi:10.1002/14651858.CD002021.pub4 [PubMed 28553701]
  18. Gubitosa JC, Terwillliger T, Ukazu A, Gordon E. Naltrexone-associated non-ST-elevated myocardial infarction. Cureus. 2020;12(10):e11198. doi:10.7759/cureus.11198 [PubMed 33269129]
  19. Hassanian-Moghaddam H, Afzali S, Pooya A. Withdrawal syndrome caused by naltrexone in opioid abusers. Hum Exp Toxicol. 2014;33(6):561-567. doi:10.1177/0960327112450901 [PubMed 23690227]
  20. Hemby SE, Johnson BA, Dworkin SI. Neurobiological basis of drug reinforcement. In: Drug Addiction and Its Treatment: Nexus of Neuroscience and Behavior. Johnson BA, Roache JD (Eds). Philadelphia, PA: Lippincott-Raven; 1997:137.
  21. Holt SR. Alcohol use disorder: pharmacologic management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 2, 2022.
  22. Kim SW, Grant JE, Yoon G, Williams KA, Remmel RP. Safety of high-dose naltrexone treatment: hepatic transaminase profiles among outpatients. Clin Neuropharmacol. 2006;29(2):77-79. doi:10.1097/00002826-200603000-00004 [PubMed 16614539]
  23. Lee YK, Park SW, Kim YK, et al. Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system. Alcohol Alcohol. 2005;40(4):297-301. doi:10.1093/alcalc/agh163. [PubMed 15897221]
  24. Legroux-Crespel E, Clèdes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology. 2004;208(4):326-330. doi:10.1159/000077841 [PubMed 15178915]
  25. Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary biliary cholangitis: 2018 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2019;69(1):394-419. doi:10.1002/hep.30145 [PubMed 30070375]
  26. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009;50(1):291-308. doi:10.1002/hep.22906 [PubMed 19554543]
  27. Lucey MR, Silverman BL, Illeperuma A, O'Brien CP. Hepatic safety of once-monthly injectable extended-release naltrexone administered to actively drinking alcoholics. Alcohol Clin Exp Res. 2008;32(3):498-504. doi:10.1111/j.1530-0277.2007.00593.x [PubMed 18241321]
  28. Malik MH, Heaton H, Sloan B. Nicolau syndrome following intramuscular naltrexone injection. Dermatol Online J. 2020;26(7):13030/qt3gb5m0vr. [PubMed 32898411]
  29. Miotto K, McCann MJ, Rawson RA, Frosch D, Ling W. Overdose, suicide attempts and death among a cohort of naltrexone-treated opioid addicts. Drug Alcohol Depend. 1997;45(1-2):131-134. doi:10.1016/s0376-8716(97)01348-3 [PubMed 9179515]
  30. Mitchell JE. Naltrexone and hepatotoxicity. Lancet. 1986;1(8491):1215. doi:10.1016/s0140-6736(86)91196-7 [PubMed 2871452]
  31. Mitchell MC, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs. 2012;73(6):991-997. doi:10.15288/jsad.2012.73.991 [PubMed 2303621]
  32. Molero Y, Zetterqvist J, Binswanger IA, Hellner C, Larsson H, Fazel S. Medications for alcohol and opioid use disorders and risk of suicidal behavior, accidental overdoses, and crime. Am J Psychiatry. 2018;175(10):970-978. doi:10.1176/appi.ajp.2018.17101112 [PubMed 30068260]
  33. Naltrexone hydrochloride tablets, USP [prescribing information]. Congers, NY: Chartwell Rx LLC; December 2021.
  34. Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study. J Am Soc Nephrol. 2000;11(3):514-519. [PubMed 10703675]
  35. Peer G, Kivity S, Agami O, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet. 1996;348(9041):1552-1554. doi:10.1016/s0140-6736(96)04176-1 [PubMed 8950882]
  36. Perli D, Martone C, Rapose A. Naltrexone-induced Nicolau syndrome masquerading as cutaneous abscess. BMJ Case Rep. 2012;2012:bcr2012007785. doi:10.1136/bcr-2012-007785 [PubMed 23242099]
  37. Reus VI, Fochtmann LJ, Bukstein O, et al. The American Psychiatric Association practice guideline for the pharmacological treatment of patients with alcohol use disorder. Am J Psychiatry. 2018;175(1):86-90. doi:10.1176/appi.ajp.2017.1750101. [PubMed 29301420]
  38. Revia (naltrexone) [product monograph]. Toronto, Ontario, Canada: Teva Canada Limited; April 2015.
  39. Sax DS, Kornetsky C, Kim A. Lack of hepatotoxicity with naltrexone treatment. J Clin Pharmacol. 1994;34(9):898-901. doi:10.1002/j.1552-4604.1994.tb04002.x [PubMed 7983232]
  40. Strain E. Pharmacotherapy for opioid use disorder. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed March 8, 2022.
  41. Substance Abuse and Mental Health Services Administration (SAMHSA). Medications for Opioid Use Disorder. Treatment Improvement Protocol (TIP) Series 63. Publication No. PEP21-02-01-002. Substance Abuse and Mental Health Services Administration; 2021. https://store.samhsa.gov/product/TIP-63-Medications-for-Opioid-Use-Disorder-Full-Document/PEP21-02-01-002. Accessed February 7, 2022.
  42. Terg R, Coronel E, Sordá J, Muñoz AE, Findor J. Efficacy and safety of oral naltrexone treatment for pruritus of cholestasis, a crossover, double blind, placebo-controlled study. J Hepatol. 2002;37(6):717-722. doi:10.1016/s0168-8278(02)00318-5 [PubMed 12445410]
  43. Tetrault JM, Tate JP, McGinnis KA, et al. Hepatic safety and antiretroviral effectiveness in HIV-infected patients receiving naltrexone. Alcohol Clin Exp Res. 2012;36(2):318-324. doi:10.1111/j.1530-0277.2011.01601.x [PubMed 21797892]
  44. Towers CV, Katz E, Weitz B, Visconti K. Use of naltrexone in treating opioid use disorder in pregnancy. Am J Obstet Gynecol. 2020;222(1):83.e1-83.e8. doi:10.1016/j.ajog.2019.07.037. [PubMed 31376396]
  45. Tran TH, Griffin BL, Stone RH, Vest KM, Todd TJ. Methadone, buprenorphine, and naltrexone for the treatment of opioid use disorder in pregnant women. Pharmacotherapy. 2017;37(7):824-839. doi:10.1002/phar.1958. [PubMed 28543191]
  46. Verma R. Naltrexone-associated acute pancreatitis. Prim Care Companion CNS Disord. 2016;18(6):10.4088/PCC.16l01953. doi:10.4088/PCC.16l01953 [PubMed 27922226]
  47. Vivitrol (naltrexone) [prescribing information]. Waltham, MA: Alkermes Inc; September 2022.
  48. Williams KL, Broadbear JH, Woods JH. Noncontingent and response-contingent intravenous ethanol attenuates the effect of naltrexone on hypothalamic-pituitary-adrenal activity in rhesus monkeys. Alcohol Clin Exp Res. 2004;28(4):566-571. [PubMed 15100607]
  49. Wolfhagen FH, Sternieri E, Hop WC, Vitale G, Bertolotti M, Van Buuren HR. Oral naltrexone treatment for cholestatic pruritus: a double-blind, placebo-controlled study. Gastroenterology. 1997;113(4):1264-1269. doi:10.1053/gast.1997.v113.pm9322521 [PubMed 9322521]
  50. Yeo M, Campbell V, Bonomo Y, Sawyer SM. Acute opioid withdrawal on accidental injection of naltrexone. J Paediatr Child Health. 2003;39(4):315-317. doi:10.1046/j.1440-1754.2003.00143.x [PubMed 12755943]
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