Naltrexone is a competitive opioid antagonist indicated for the management of alcohol dependence and the prevention of relapse to opioid dependence following opioid detoxification. It functions by binding to opioid receptors, effectively blocking the euphoric and sedative effects of opioids and reducing the craving for alcohol. Available in oral and extended-release injectable formulations, naltrexone represents a cornerstone of medication-assisted treatment (MAT) when used as part of a comprehensive treatment plan that includes counseling and psychosocial support. Its efficacy is well-documented in clinical trials, supporting its role in helping patients maintain abstinence and improve long-term outcomes.

Features

• Mechanism of Action: Pure opioid receptor antagonist; competitively binds to mu, kappa, and delta opioid receptors.
• Formulations: Available as 50 mg oral tablets and a 380 mg extended-release intramuscular injection (Vivitrol®).
• Bioavailability: Oral bioavailability ranges from 5–40% due to significant first-pass metabolism.
• Half-Life: Oral naltrexone has a half-life of approximately 4 hours; its primary metabolite, 6-β-naltrexol, has a half-life of 13 hours. The injectable formulation provides sustained release over approximately 4 weeks.
• Metabolism: Primarily hepatic, via dihydrodiol dehydrogenase and subsequent glucuronide conjugation.
• Excretion: Mainly renal (approximately 60%), with the remainder excreted in feces.

Benefits

• Reduces Craving: Demonstrated efficacy in decreasing the subjective craving for alcohol and opioids, supporting abstinence.
• Blocks Opioid Effects: Prevents the euphoric and analgesic effects of illicit opioids, reducing the reinforcing properties of use.
• Non-Addictive: Lacks abuse potential and does not produce physical dependence, making it suitable for long-term maintenance.
• Flexible Administration: Availability of both daily oral and monthly injectable formulations allows for personalized treatment plans.
• Supports Psychosocial Therapy: Serves as an effective pharmacological adjunct to counseling and behavioral interventions.
• Improves Treatment Retention: Associated with higher rates of continued engagement in comprehensive treatment programs.

Common use

Naltrexone is primarily prescribed for two indications: as part of a treatment program for alcohol dependence in adults who have been able to abstain from alcohol in an outpatient setting prior to initiation of therapy, and for the blockade of the effects of exogenously administered opioids in patients who have undergone complete opioid detoxification. It is used off-label in certain cases of impulse control disorders and autoimmune conditions, though such uses require careful clinical consideration and are not FDA-approved.

Dosage and direction

For alcohol dependence: Initiate with 25 mg orally once daily to assess tolerability, then increase to the recommended dose of 50 mg once daily. The extended-release injectable formulation is administered as 380 mg intramuscularly every 4 weeks.

For opioid dependence: Treatment should only be initiated after a patient has remained opioid-free for a minimum of 7–10 days. The recommended oral dose is 50 mg once daily. Alternatively, 380 mg of the extended-release injectable may be administered every 4 weeks.

Administration with or after food may minimize gastrointestinal upset. The oral tablet should be taken as directed, typically once daily. The injectable form must be administered by a healthcare professional into the gluteal muscle.

Precautions

• Hepatotoxicity: Use with caution in patients with acute hepatitis or liver failure; periodic liver function tests are recommended.
• Opioid Abstinence: Patients must be opioid-free at initiation to avoid precipitating acute withdrawal.
• Depression and Suicidality: Monitor for emergence or worsening of depression, suicidal ideation, or unusual changes in behavior.
• Renal Impairment: Dose adjustment may be necessary in severe renal impairment.
• Accidental Injury: May cause dizziness or sedation; advise patients to avoid driving or operating machinery until they know how naltrexone affects them.
• Pregnancy and Lactation: Use only if the potential benefit justifies the potential risk to the fetus or infant.

Contraindications

• Patients receiving opioid analgesics, currently dependent on opioids, or in acute opioid withdrawal.
• Positive urine screen for opioids.
• Acute hepatitis or liver failure.
• History of hypersensitivity to naltrexone or any component of the formulation (e.g., polylactide-co-glycolide microspheres in the injectable).
• Failure to pass a naloxone challenge test prior to initiation (if required per protocol).

Possible side effect

Common adverse reactions (≥5%) include:

• Nausea
• Headache
• Dizziness
• Nervousness
• Fatigue
• Insomnia
• Vomiting
• Anxiety

Less common but serious side effects may include:

• Hepatotoxicity (elevated transaminases, jaundice)
• Injection site reactions (for extended-release form): induration, tenderness, bruising, pruritus, nodule formation
• Eosinophilic pneumonia (rare, associated with injectable form)
• Suicidal ideation and behavior
• Severe depression

Drug interaction

• Opioid-containing medications: Naltrexone will block the effects of opioid analgesics, antitussives, or antidiarrheals. Larger doses of opioids may overcome this blockade, increasing risk of fatal respiratory depression.
• Opioid dependence treatments: Do not use concurrently with methadone or buprenorphine, as naltrexone will precipitate withdrawal.
• CNS depressants: Additive sedation may occur with alcohol, benzodiazepines, or other sedatives.
• Medications metabolized by CYP enzymes: Potential for interaction, though clinical significance is uncertain.

Missed dose

If a dose of oral naltrexone is missed, it should be taken as soon as remembered unless it is almost time for the next dose. In that case, skip the missed dose and resume the usual dosing schedule. Do not double the dose. For the extended-release injection, administer the next dose as soon as possible and resume the every-4-week schedule.

Overdose

No specific antidote exists. In cases of suspected overdose, provide symptomatic and supportive care. Hemodialysis is not expected to enhance elimination. Note: Overdose of naltrexone itself is not typically life-threatening, but patients may experience intensified adverse effects such as nausea, abdominal pain, dizziness, or sedation. If opioids are used in an attempt to overcome naltrexone blockade, life-threatening opioid overdose may occur due to the requirement for excessively high and unpredictable opioid doses.

Storage

Store at controlled room temperature (20–25°C or 68–77°F). Oral tablets should be kept in a tightly closed container. The extended-release injectable kit must be refrigerated (2–8°C or 36–46°F) and allowed to reach room temperature prior to administration. Do not freeze. Keep out of reach of children and pets.

Disclaimer

This information is intended for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here.

Reviews

“Naltrexone has been a critical component of our MAT program. The monthly injectable formulation significantly improves adherence and has helped many of our patients maintain long-term sobriety where daily dosing was a barrier.” – Addiction Specialist, MD

“Patients report a noticeable reduction in alcohol cravings within the first few weeks of treatment. It’s most effective when combined with consistent counseling.” – Clinical Psychologist

“While the injectable form is advantageous for compliance, injection site reactions can be a concern. Proper technique and rotation are essential.” – Registered Nurse, MAT Clinic

“The requirement for full opioid detoxification prior to initiation remains a clinical challenge, but for those who successfully transition, naltrexone provides a safe and effective maintenance option.” – Psychiatric Pharmacist