Can patients be on scheduled oxycodone (opioid agonist) if they have naltrexone (opioid antagonist) ordered?

No, Patients Should Not Be on Scheduled Oxycodone While Taking Naltrexone

Concomitant use of opioid antagonists like naltrexone with opioid agonists like oxycodone should be avoided, as naltrexone blocks opioid analgesic effects and can precipitate severe opioid withdrawal. 1

Pharmacological Incompatibility

Naltrexone competitively antagonizes mu, kappa, and delta opioid receptors, directly blocking the therapeutic effects of oxycodone. 2 This means:

• Patients on naltrexone will not experience pain relief from oxycodone, rendering the scheduled opioid completely ineffective 3
• The opioid blockade makes opioid analgesics therapeutically futile 1

Risk of Precipitated Withdrawal

If a patient has any opioid dependence or recent opioid exposure, administering naltrexone can precipitate severe, potentially life-threatening withdrawal requiring hospitalization. 3 The Society for Perioperative Assessment and Quality Improvement specifically warns that concomitant use results in reduced opioid efficacy and can precipitate opioid withdrawal 1

Key withdrawal considerations:

• Withdrawal symptoms can appear within 5 minutes and last up to 48 hours 3
• Severe cases may require intensive care unit management with significant fluid losses from vomiting and diarrhea 3
• Mental status changes including confusion, somnolence, and visual hallucinations can occur 3
• Precipitated withdrawal has been documented even in patients with negative urine toxicology screens 4, 5

Required Medication Discontinuation Timeline

Before starting naltrexone, patients must be completely opioid-free for a minimum of 7-10 days for short-acting opioids like oxycodone. 1, 3 The FDA label explicitly states patients should not take naltrexone if they have any symptoms of opioid withdrawal and must notify healthcare providers of any recent opioid use 3

Conversely, if naltrexone needs to be discontinued to allow opioid use:

• Oral naltrexone should be held 3-4 days before opioids are needed 1
• Extended-release naltrexone (Vivitrol) must be held 24-30 days after the last injection 1, 2

Clinical Management Algorithm

If both medications are ordered simultaneously, this represents a medication error requiring immediate intervention:

1. Verify the clinical indication for each medication with the prescribing physician 3
2. Discontinue one medication based on the primary treatment goal:
   • If treating opioid/alcohol dependence: discontinue oxycodone and use alternative non-opioid pain management 2, 3
   • If treating acute pain requiring opioids: discontinue naltrexone with appropriate washout period 1
3. Assess for opioid dependence before any changes, as abrupt discontinuation of either medication carries risks 3

Alternative Pain Management Strategies

Patients on naltrexone requiring analgesia need non-opioid alternatives, as they will not benefit from opioid-containing medications 3. The FDA label explicitly warns that patients taking naltrexone may not benefit from opioid analgesics 3

Critical Safety Warning

After naltrexone discontinuation, patients have markedly reduced opioid tolerance and are at high risk of fatal overdose if they use previously tolerated opioid doses. 3 Cases of opioid overdose with fatal outcomes have been reported in patients after discontinuing naltrexone treatment 3

Common Pitfall

A false-positive oxycodone urine drug screen can occur in patients taking oral naltrexone due to the metabolite noroxymorphone 6. This should not be confused with actual oxycodone use and requires confirmatory testing 6. However, this metabolite does not provide analgesia and does not change the fundamental incompatibility of these medications.