What is the treatment for naltrexone toxicity?

Treatment of Naltrexone Toxicity

The treatment of naltrexone toxicity is primarily supportive care with close monitoring in a healthcare setting, as there is no specific antidote available. 1

Clinical Presentation of Naltrexone Toxicity

• High doses of naltrexone (generally ≥1,000 mg/kg in animal studies) can produce symptoms including salivation, depression/reduced activity, tremors, and convulsions 1
• Mortality in animal studies due to high-dose naltrexone administration typically results from clonic-tonic convulsions and/or respiratory failure 1
• In humans, limited clinical experience with naltrexone overdose exists, but subjects who received 800 mg daily (16 times the standard dose) for up to one week showed no evidence of toxicity 1

Treatment Algorithm

Immediate Management

• Provide symptomatic treatment in a closely supervised environment 1
• Contact poison control center for the most up-to-date management information 1
• Monitor vital signs, with particular attention to respiratory status due to potential respiratory failure seen in animal studies 1
• Treat seizures if they occur, as convulsions are a documented effect of high-dose naltrexone in animal studies 1

Supportive Care

• Provide positive pressure ventilation if severe pulmonary edema develops 2
• Monitor for and manage potential complications including:
  • Tremors 1
  • Depression/reduced activity 1
  • Convulsions 1

Special Considerations

For Patients on Chronic Opioids

• Be aware that naltrexone administration to patients using chronic opioids can cause acute and severe withdrawal symptoms, including bone and muscle pain 3
• Abrupt reversal of opioid effects in opioid-tolerant patients may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, pulmonary edema, cardiac arrhythmias, and in severe cases, cardiac arrest 3

For Patients with Recurrent Opioid Toxicity

• If the patient has been receiving naltrexone for opioid use disorder and develops recurrent opioid toxicity, repeated small doses or an infusion of naltrexone can be beneficial 2
• After return of spontaneous breathing, patients should be observed in a healthcare setting until the risk of recurrent opioid toxicity is low and the patient's level of consciousness and vital signs have normalized 2

Monitoring and Follow-up

• Liver function tests should be performed as naltrexone has potential hepatotoxicity at supratherapeutic doses 4
• Monitor for neuropsychiatric adverse effects, especially in individuals younger than 24 years, as bupropion (often combined with naltrexone) is an antidepressant 2

Prevention of Naltrexone Toxicity

• Patients using naltrexone should be educated about proper dosing and potential risks 4
• For patients requiring opioids for pain control, naltrexone should be discontinued as it blocks pain relief from opioid agonists 4
• Oral naltrexone should be held for 3-4 days prior to elective procedures if opioids are expected, and intramuscular naltrexone should be held 24-30 days after the last injection before elective procedures 3

Pitfalls and Caveats

• Do not administer opioids to counteract naltrexone toxicity, as naltrexone is an opioid antagonist and will block their effects 3, 4
• Be aware that patients who discontinue naltrexone treatment have increased risk of opioid overdose and death due to decreased opioid tolerance if they return to opioid use 4
• Liver enzyme control tests should be carried out before and during treatment with naltrexone 5