Important Safety Information — Naltrexone

Indications

Naltrexone hydrochloride is an opioid antagonist. At standard doses, it is FDA-approved for the treatment of alcohol dependence and for the blockade of the effects of exogenously administered opioids. Low-dose naltrexone (LDN) is used off-label for various conditions including chronic pain, inflammation, and general wellness support. Off-label use is not FDA-approved.

Contraindications

• Patients currently receiving opioid analgesics or in acute opioid withdrawal
• Any individual who has failed the naloxone challenge test or has a positive urine screen for opioids
• Patients with acute hepatitis or liver failure
• Known hypersensitivity to naltrexone hydrochloride or any component of the formulation

Warnings and Precautions

• Hepatotoxicity: Naltrexone can cause hepatocellular injury. Monitor liver function tests before and during treatment. Discontinue use if signs or symptoms of acute hepatitis develop.
• Opioid blockade: Naltrexone blocks the effects of opioid-containing medicines, including those prescribed for pain, cough, colds, or diarrhea. Patients must inform all healthcare providers that they are taking naltrexone, as attempts to overcome the opioid blockade by using large amounts of opioids can lead to life-threatening opioid intoxication or fatal overdose.
• Opioid withdrawal: Initiating naltrexone in patients who are dependent on opioids can precipitate acute, severe withdrawal symptoms. An opioid-free interval of at least 7-10 days is recommended before starting naltrexone.
• Surgery: Patients requiring pain management for planned surgery should discontinue naltrexone at least 72 hours (for standard doses) or at least 7 days (recommended for LDN) before the procedure. Regional analgesia, non-opioid analgesics, or general anesthesia may be needed.
• Depression and suicidality: Depression and suicidal behavior have been reported in patients treated with naltrexone. Monitor patients for the emergence of depressive symptoms.
• Injection site reactions: If administered by injection, reactions at the injection site may occur.

Common Side Effects

Side effects with low-dose naltrexone (LDN) are generally uncommon due to the lower dose. Reported side effects include:

• Difficulty sleeping or insomnia (reported in approximately 8% of LDN users; usually resolves within 2 weeks)
• Vivid or unusual dreams
• Nausea
• Headache
• Anxiety
• Fatigue
• Dizziness
• Abdominal pain or cramping
• Decreased appetite

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

• Signs of liver problems: yellowing of the skin or whites of the eyes (jaundice), dark urine, persistent stomach pain, unusual fatigue
• Signs of opioid withdrawal: abdominal cramping, nausea, vomiting, diarrhea, muscle aches, joint pain, anxiety, irritability, runny nose, fever, sweating, goosebumps
• Depression or suicidal thoughts
• Signs of allergic reaction: rash, hives, swelling of the face, lips, tongue, or throat, difficulty breathing
• Severe injection site reaction with signs of infection (if applicable)
• Pneumonia (reported with extended-release formulation)

Drug Interactions

• Opioid analgesics (e.g., codeine, hydrocodone, oxycodone, morphine, fentanyl): Naltrexone blocks the effects of opioid medications. Do not take opioid pain medications while on naltrexone. Attempting to overcome the blockade with high doses of opioids can result in fatal overdose.
• Opioid-containing cough, cold, or anti-diarrheal medications: These will be ineffective while taking naltrexone.
• Disulfiram: The safety and efficacy of concomitant use is unknown. Concurrent use of two potentially hepatotoxic medications is not ordinarily recommended.
• Thioridazine: May interact with naltrexone. Inform your provider.
• Other hepatotoxic medications: Concurrent use with medications known to cause liver damage should be carefully considered.

Use in Specific Populations

• Pregnancy: There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.
• Lactation: It is not known whether naltrexone is excreted in human breast milk. Caution should be exercised when administering to a nursing woman.
• Pediatric use: Safety and effectiveness in patients under 18 years of age have not been established.
• Geriatric use: Clinical studies did not include sufficient numbers of subjects 65 and older. Use with caution and monitor liver function.
• Hepatic impairment: Contraindicated in acute hepatitis or liver failure. Use with caution in patients with liver disease; monitor liver function tests frequently.
• Renal impairment: Naltrexone and its metabolite are excreted primarily by the kidneys. Dose adjustment may be needed in patients with renal impairment.