Should naltrexone be avoided in individuals using chronic opioids?

Naltrexone Should Be Avoided in Patients Using Chronic Opioids

Naltrexone is absolutely contraindicated in patients receiving chronic opioid therapy as it can precipitate severe opioid withdrawal and block analgesic effects of opioids. 1

Mechanism and Contraindication

• Naltrexone is a competitive opioid receptor antagonist that blocks the euphoric effects of opioids by acting at the μ- and κ-opioid receptors 2
• The FDA explicitly lists patients receiving opioid analgesics and those currently dependent on opioids (including those maintained on methadone or buprenorphine) as contraindications for naltrexone therapy 1
• Concomitant use of opioid antagonists with opioids should be avoided in the absence of clinically significant respiratory depression as it results in reduced opioid efficacy and can precipitate opioid withdrawal 3

Risks of Concurrent Use

• Administration of naltrexone to patients using chronic opioids can cause acute and severe withdrawal symptoms, including 2:

  • Agitation (96.2% of patients)
  • Altered level of consciousness (38.6%)
  • Nausea and vomiting (>27%)
  • Abdominal pain (24.2%)
  • Diarrhea (16.7%)
  • Bone and muscle pain (15.9%)
  • Tachycardia (12.9%)

• Abrupt reversal of opioid effects in opioid-tolerant patients may result in 3:

  • Nausea, vomiting, sweating
  • Tachycardia, increased blood pressure
  • Tremulousness and seizures
  • Pulmonary edema, cardiac arrhythmias, and cardiac arrest (in severe cases)

Clinical Recommendations

• Patients must be completely opioid-free before starting naltrexone to avoid precipitation of withdrawal 4
• For oral naltrexone, patients should be off all opioids, including opioid-containing medicines, for a minimum of 7 to 10 days before starting treatment 1
• For extended-release injectable naltrexone (Vivitrol), patients transitioning from buprenorphine or methadone may be vulnerable to precipitation of withdrawal symptoms for as long as two weeks 4

Perioperative Considerations

• If a patient on naltrexone requires surgery or procedures requiring opioid analgesia 1:
  • Oral naltrexone should be held for 3-4 days prior to elective procedures 3
  • Intramuscular naltrexone should be held 24-30 days after the last injection before elective procedures 3

Alternative Options for Patients Requiring Both Pain Management and Addiction Treatment

• For patients with chronic pain who also have opioid use disorder, consider alternative non-opioid pain management strategies 4
• Buprenorphine may be an option for some patients as it has both analgesic properties and is effective for opioid use disorder treatment 3
• For patients with alcohol use disorder who also require chronic opioid therapy, medications such as acamprosate or disulfiram may be considered instead of naltrexone 4

Patient Education

• Patients should be informed that naltrexone blocks the effects of opioids and can render opioid pain medications ineffective 1
• Patients should carry identification to alert medical personnel that they are taking naltrexone to ensure adequate treatment in emergencies 1
• Patients should be warned that attempting to overcome the opioid blockade by taking large amounts of opioids could lead to serious injury, coma, or death 1

Naltrexone remains a valuable medication for alcohol use disorder and opioid use disorder in patients who are fully detoxified from opioids, but its antagonist mechanism makes it fundamentally incompatible with ongoing opioid therapy for pain management 4, 5.