Naltrexone is an opioid antagonist medication primarily indicated for the management of alcohol dependence and the prevention of relapse to opioid dependence following opioid detoxification. As a competitive antagonist, it binds to opioid receptors without activating them, effectively blocking the euphoric and sedative effects of opioids. When used as part of a comprehensive treatment program that includes counseling and psychosocial support, naltrexone helps reduce cravings and supports long-term recovery. It is available in both oral tablet and extended-release injectable formulations, providing flexibility in treatment approaches based on individual patient needs and compliance considerations.

Features

• Available in 50 mg oral tablets and 380 mg extended-release intramuscular injection
• Competitive opioid receptor antagonist with high affinity for mu-opioid receptors
• Non-addictive with no abuse potential or development of tolerance
• Hepatically metabolized via glucuronidation with renal excretion of metabolites
• FDA-approved for alcohol use disorder and opioid use disorder maintenance
• Can be administered without regard to meals due to minimal food effect on absorption

Benefits

• Significantly reduces alcohol consumption and increases abstinence rates in alcohol-dependent patients
• Blocks the euphoric effects of opioids, reducing the risk of relapse in opioid-dependent individuals
• Decreases cravings for both alcohol and opioids through modulation of the endogenous opioid system
• Provides flexible dosing options with once-daily oral or monthly injectable formulations
• Non-controlled substance status eliminates concerns about diversion or abuse
• Compatible with comprehensive behavioral therapy programs for enhanced treatment outcomes

Common use

Naltrexone is primarily prescribed for the management of alcohol dependence in patients who have achieved abstinence and wish to remain alcohol-free. It is equally important in preventing relapse to opioid dependence following complete detoxification from opioids. The medication is typically initiated after a minimum 7-10 day opioid-free period to avoid precipitating withdrawal symptoms. Clinicians may also consider naltrexone off-label for certain impulse control disorders, though this use requires careful risk-benefit assessment. Treatment is most effective when combined with comprehensive psychosocial support, including cognitive behavioral therapy, motivational enhancement, and participation in support groups.

Dosage and direction

Oral formulation: Therapy is initiated with 25 mg daily for the first day to assess tolerance, then increased to the maintenance dose of 50 mg once daily. The tablet may be administered with or without food. For alcohol dependence, treatment duration typically ranges from 3 to 12 months based on individual response.

Injectable formulation: The extended-release injection is administered intramuscularly by a healthcare professional every 4 weeks or once monthly. The recommended dose is 380 mg delivered as a gluteal intramuscular injection, with careful attention to proper injection technique to avoid injection site reactions.

Dosage adjustments may be necessary for patients with hepatic impairment, though alternative treatments are generally preferred in severe liver disease. Renal impairment does not typically require dosage adjustment.

Precautions

Patients must be completely free of opioids for at least 7-10 days before initiating naltrexone therapy to avoid precipitated withdrawal. Liver function tests should be obtained at baseline and monitored periodically during treatment, particularly with the oral formulation. Use with caution in patients with hepatic impairment or acute hepatitis. Patients should carry documentation of naltrexone use, as it may affect pain management requirements in emergency situations. Healthcare providers should educate patients that attempting to overcome the opioid blockade by taking large amounts of opioids could lead to fatal respiratory depression. Compliance with the medication regimen is essential for therapeutic efficacy, particularly with the oral formulation.

Contraindications

Naltrexone is contraindicated in patients receiving opioid analgesics, those with current physiologic opioid dependence, or those in acute opioid withdrawal. It is contraindicated in patients with acute hepatitis or liver failure. The medication should not be administered to patients who have failed the naloxone challenge test or who have a positive urine screen for opioids. Hypersensitivity to naltrexone or any component of the formulation constitutes an absolute contraindication. The injectable formulation is additionally contraindicated in patients with allergy to polylactide-co-glycolide (PLG) or any other component of the diluent.

Possible side effects

Common (≥5%): Nausea (10%), headache (7%), dizziness (4-10%), insomnia (3-9%), anxiety (2-7%), vomiting (3-7%) Less common (1-5%): Fatigue, decreased appetite, joint/muscle pain, somnolence, toothache Injectable-specific: Injection site reactions including pain, tenderness, induration, swelling, erythema, or bruising (occur in approximately 30% of patients) Rare (<1%): Hepatic transaminase elevations, eosinophilic pneumonia (with injectable form), suicidal ideation, depression Most side effects are mild to moderate and tend to diminish with continued therapy. Nausea may be mitigated by taking the medication with food or dividing the dose.

Drug interaction

Naltrexone may precipitate acute withdrawal in opioid-dependent patients receiving opioid agonists (morphine, oxycodone, hydrocodone, methadone, buprenorphine). It may reduce the efficacy of opioid-containing medications, including some cough preparations and antidiarrheal agents. Concurrent use with hepatotoxic drugs (including certain anticonvulsants, antipsychotics, and antimicrobials) may increase the risk of liver injury. Caution is advised when administering with drugs that undergo extensive hepatic metabolism. No clinically significant interactions have been observed with antidepressants, benzodiazepines, or most other psychotropic medications commonly used in addiction treatment.

Missed dose

Oral formulation: If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next dose. Patients should not double the dose to make up for a missed dose. Consistent daily dosing is important for maintaining receptor blockade.

Injectable formulation: The extended-release injection is administered by healthcare professionals on a monthly schedule. If an appointment is missed, it should be rescheduled as soon as possible. The protective effects of the injection may begin to diminish if the dosing interval extends significantly beyond 4 weeks.

Overdose

There is no specific antidote for naltrexone overdose. In massive overdose, supportive measures should be instituted including gastric lavage if ingestion was recent. Since naltrexone is not an opioid agonist, respiratory depression is not expected. However, patients attempting to override the opioid blockade by consuming large amounts of opioids are at risk of life-threatening opioid overdose. In cases of injectable formulation overdose, the extended-release nature means effects may persist for weeks. Hemodialysis is not expected to enhance elimination significantly due to naltrexone’s large volume of distribution and extensive protein binding.

Storage

Store at controlled room temperature (20-25°C or 68-77°F). Oral tablets should be kept in their original container with the lid tightly closed and protected from moisture. The injectable formulation must be refrigerated at 2-8°C (36-46°F) and protected from light. The un-reconstituted product may be stored at room temperature for no more than 7 days. Once mixed, the suspension must be administered immediately. Keep all medications out of reach of children and pets.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Naltrexone should only be used under the supervision of a qualified healthcare provider who can assess individual patient needs and monitor treatment response. Patients should not initiate or discontinue naltrexone without medical guidance. The prescribing physician should be consulted for complete information regarding indications, dosage, warnings, and precautions specific to individual circumstances.

Reviews

Clinical studies demonstrate that naltrexone significantly improves treatment outcomes when incorporated into comprehensive addiction treatment programs. Systematic reviews and meta-analyses indicate that oral naltrexone reduces relapse risk in opioid dependence by approximately 30-50% compared to placebo. For alcohol dependence, naltrexone has shown a number needed to treat of 12-20 for prevention of relapse to heavy drinking. The extended-release formulation demonstrates superior adherence rates compared to daily oral dosing, with corresponding improvements in treatment outcomes. Real-world evidence supports the effectiveness of naltrexone in reducing healthcare utilization and costs associated with substance use disorders.