Naltrexone: Important Safety Information (ISI)

Read this information carefully before starting naltrexone. Discuss any questions with your provider.

What Is Naltrexone?

Naltrexone is an opioid receptor antagonist FDA-approved for the treatment of alcohol use disorder and for blockade of exogenous opioid effects in opioid use disorder. It is also prescribed off-label at low doses (LDN, 1.5–4.5 mg) for inflammatory and autoimmune conditions, and is a component of Contrave® (naltrexone HCl 8 mg + bupropion HCl 90 mg), an FDA-approved combination for chronic weight management. Available as oral tablets and as an extended-release intramuscular injection (Vivitrol®).

Boxed Warning

WARNING: HEPATOTOXICITY. Cases of hepatitis and clinically significant liver dysfunction have been observed in association with naltrexone exposure during clinical trials and in postmarketing reports, particularly at doses higher than the FDA-approved range. Naltrexone has the capacity to cause hepatocellular injury when given in excessive doses. Discontinue naltrexone in the event of symptoms or signs of acute hepatitis.

Contraindications

• Current physiologic dependence on opioids or current use of opioid analgesics (precipitates severe withdrawal)
• Acute opioid withdrawal
• Anticipated need for opioid analgesia within the next 7 to 10 days
• Failed naloxone challenge test or positive urine screen for opioids
• History of sensitivity to naltrexone or any product components

Warnings and Precautions

• Vulnerability to Opioid Overdose: Patients can lose tolerance after naltrexone treatment, increasing risk of fatal overdose if they return to opioid use. Counsel patients and family members.
• Hepatotoxicity: Periodic liver function monitoring recommended. Discontinue if signs of acute hepatitis develop.
• Depression and Suicidality: Reported during postmarketing surveillance. Monitor for mood changes and suicidal ideation.
• Injection Site Reactions: (Vivitrol® formulation) Serious reactions including necrosis reported. Use proper administration technique.
• Eosinophilic Pneumonia: Rare cases reported. Evaluate patients with progressive dyspnea or hypoxemia.
• Hypersensitivity Reactions: Including angioedema and anaphylaxis reported. Discontinue if suspected.

Most Common Adverse Reactions

Most common adverse reactions reported in clinical trials:

• Nausea
• Headache
• Dizziness
• Fatigue
• Insomnia
• Anxiety
• Vomiting
• Decreased appetite
• Abdominal pain or cramping

Drug Interactions

Naltrexone is a complete opioid antagonist and will block the analgesic effect of opioid pain medications and precipitate severe withdrawal in opioid-dependent patients. Use of naltrexone with thioridazine has been associated with increased somnolence and lethargy. Patients who require opioid analgesia for emergency pain management may need higher doses of opioids and require specialized monitoring.

Use in Specific Populations

• Pregnancy: Limited human data. Use only if potential benefit justifies potential fetal risk.
• Lactation: Naltrexone and 6-beta-naltrexol are present in human milk. Consider risk and benefit.
• Pediatric Use: Safety and effectiveness not established.
• Hepatic Impairment: Use with caution. Avoid in patients with acute hepatitis or liver failure.
• Renal Impairment: Use with caution; pharmacokinetics in patients with severe renal impairment have not been adequately studied.