What happens when oxycodone is taken with naltrexone?

Interaction Between Oxycodone and Naltrexone

When oxycodone is taken with naltrexone, the naltrexone will block the analgesic effects of oxycodone and may precipitate opioid withdrawal in opioid-dependent individuals, potentially leading to severe adverse outcomes including respiratory depression if patients attempt to overcome the blockade. 1

Mechanism of Interaction

Naltrexone is a potent opioid receptor antagonist that competitively binds to opioid receptors, blocking the effects of opioids like oxycodone. This interaction occurs through:

• Competitive binding: Naltrexone has high affinity for mu opioid receptors (the primary target of oxycodone), effectively preventing oxycodone from exerting its analgesic effects 1
• Duration of blockade: Standard doses of naltrexone (50 mg) can block opioid effects for up to 24 hours; doubling the dose extends blockade to 48 hours 1
• Surmountable blockade: While naltrexone creates a strong blockade, it is theoretically possible to overcome this blockade with very high doses of opioids, which creates significant risk 1

Clinical Consequences

1. Loss of Analgesia

• Patients taking naltrexone will not experience pain relief from oxycodone
• This blockade affects all opioid-mediated effects including analgesia, euphoria, and respiratory depression 1

2. Risk of Withdrawal

• In opioid-dependent individuals, naltrexone can precipitate severe withdrawal symptoms when administered with or after oxycodone 1
• Withdrawal symptoms may appear within 5 minutes of naltrexone ingestion and last up to 48 hours 1
• Severe cases may require hospitalization and even intensive care management 1

3. Risk of Overdose

• Patients may attempt to overcome naltrexone's blockade by taking excessive amounts of oxycodone, which can lead to:

  • Life-threatening opioid intoxication
  • Respiratory depression or arrest
  • Circulatory collapse
  • Fatal overdose 1

• After discontinuing naltrexone, patients have reduced opioid tolerance and are at increased risk of overdose if they resume previous opioid doses 1, 2

Special Considerations

Therapeutic Applications

Some specific formulations combine opioids with antagonists for therapeutic purposes:

• Prolonged-release oxycodone/naloxone: This combination is designed to reduce opioid-induced constipation while maintaining analgesia 2

  • The naloxone component acts locally in the gut to block opioid receptors
  • Studies show significant improvements in bowel function without loss of analgesic efficacy 2

• Ultra-low-dose naltrexone with oxycodone (Oxytrex): This investigational combination was designed to minimize physical dependence while providing analgesia 3

  • Contains very small amounts of naltrexone (1-2 μg per dose)
  • Clinical development has been discontinued due to marginal differences compared to oxycodone alone 4

Perioperative Management

For patients on naltrexone requiring surgery:

• Oral naltrexone should be discontinued 2-3 days before elective surgical procedures if opioids will be needed for pain management 2
• The active metabolite (6-β-naltrexol) has a half-life of 13 hours and may persist for 2-3 days 2
• Alternative pain management strategies should be considered

Clinical Recommendations

1. Never administer oxycodone to patients currently taking naltrexone for addiction treatment unless in a controlled setting with appropriate monitoring 1

2. Educate patients on naltrexone about:

   • The futility of taking opioids while on naltrexone
   • The dangers of attempting to overcome the blockade
   • Increased sensitivity to opioids after discontinuing naltrexone 1

3. For patients requiring pain management while on naltrexone:

   • Use non-opioid analgesics
   • Consider regional anesthesia techniques when appropriate
   • If opioids are absolutely necessary, discontinue naltrexone 2-3 days prior and use careful monitoring 2

4. For opioid-induced constipation management:

   • Consider peripherally acting mu opioid receptor antagonists (PAMORAs) like naloxegol or methylnaltrexone instead of naltrexone 2

5. Be aware of false-positive urine drug screens:

   • Naltrexone metabolism can produce noroxymorphone, which may cause false-positive results for oxycodone on urine drug screens 5
   • Confirmatory testing should be performed when this is suspected

The interaction between oxycodone and naltrexone represents a significant clinical concern that requires careful management to prevent serious adverse outcomes related to both ineffective pain control and potential overdose risks.