Naltrexone

• Alcohol Use Disorder
• Opioid Use Disorder
• Addiction Treatment

Naltrexone is an opioid antagonist used to treat alcohol use disorder and prevent relapse in opioid use disorder after detoxification. By blocking opioid receptors, it reduces the rewarding effects of alcohol and opioids, helping patients maintain abstinence.

Mechanism of Action

Naltrexone competitively binds to opioid receptors (primarily mu, with some kappa and delta activity):

• In opioid use disorder: Blocks the euphoric effects of opioids, reducing motivation to use
• In alcohol use disorder: Blocks endogenous opioid release triggered by alcohol, reducing the pleasurable effects and cravings

Unlike methadone or buprenorphine, naltrexone has no agonist activity and does not produce euphoria, physical dependence, or tolerance.

Available Formulations

• Oral tablets: 50 mg (daily dosing)
• Extended-release injectable suspension (Vivitrol): 380 mg IM every 4 weeks

The injectable form improves compliance by eliminating daily dosing decisions.

Medical Uses

FDA-Approved Indications:

• Alcohol use disorder (both formulations)
• Prevention of relapse to opioid dependence after opioid detoxification (both formulations)

Naltrexone is most effective as part of a comprehensive treatment program including counseling and psychosocial support.

Dosing Guidelines

Alcohol Use Disorder:

• Oral: 50 mg once daily
• IM: 380 mg every 4 weeks (gluteal injection, alternating sides)

Opioid Use Disorder:

• Oral: 50 mg once daily (or alternative regimens: 100 mg Monday/Wednesday, 150 mg Friday)
• IM: 380 mg every 4 weeks

Critical Requirement: Patient must be opioid-free for 7-10 days before starting naltrexone to avoid precipitated withdrawal. Urine drug screen and/or naloxone challenge recommended.

Important Safety Information

Black Box Warning (Injectable):

• Risk of hepatotoxicity
• Vulnerable to opioid overdose after discontinuation due to reduced tolerance

Contraindications:

• Current opioid use or dependence
• Acute opioid withdrawal
• Positive urine screen for opioids
• Acute hepatitis or liver failure
• Prior hypersensitivity to naltrexone

Warnings and Precautions:

• Hepatotoxicity: Monitor liver function
• Precipitation of opioid withdrawal if opioids present
• Patients should carry wallet card indicating naltrexone use
• Large opioid doses to overcome blockade can cause fatal overdose
• Depression and suicidality: Monitor closely

Drug Interactions

• Opioid analgesics: Blocked by naltrexone; higher doses needed for pain control (dangerous)
• Opioid-containing products: Avoid cough syrups, antidiarrheals with opioids
• Thioridazine: Increased lethargy and somnolence

Special Populations

• Hepatic Impairment: Use with caution; monitor liver function
• Renal Impairment: Use with caution in severe impairment
• Pregnancy: Use only if benefit outweighs risk
• Elderly: No specific adjustments but increased monitoring recommended

Overdose Management

Patients on naltrexone who require emergency analgesia present challenges:

• Higher opioid doses needed (with respiratory monitoring)
• Regional anesthesia, non-opioid analgesics, and general anesthesia preferred
• Consult pain management specialists