Can naltrexone (opioid receptor antagonist) and oxazepam (benzodiazepine) be prescribed together?

Naltrexone and Oxazepam Can Be Safely Prescribed Together

Yes, naltrexone and oxazepam can be prescribed together, as there are no significant contraindications between these medications. While naltrexone is an opioid receptor antagonist and oxazepam is a benzodiazepine, they work on different receptor systems and do not have direct pharmacological interactions that would prevent their concurrent use 1, 2.

Pharmacological Considerations

• Naltrexone acts primarily as an opioid receptor antagonist, blocking the effects of opioids by competitive inhibition at mu, kappa, and delta opioid receptors 1, 3
• Oxazepam, like other benzodiazepines, works by enhancing the effect of gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in sedative, anxiolytic, and muscle relaxant effects 1
• Unlike the dangerous combination of opioid agonists with benzodiazepines, naltrexone (an opioid antagonist) with benzodiazepines does not carry the same risk of respiratory depression 4

Clinical Evidence Supporting Combined Use

• Research has demonstrated that naltrexone can be safely combined with benzodiazepines, with one study showing that naltrexone plus the benzodiazepine prazepam was more effective than naltrexone alone in keeping opioid-dependent patients abstinent 2
• The combination of naltrexone and benzodiazepines has been studied in clinical settings without reports of significant adverse interactions 2, 5
• Some evidence suggests that naltrexone may actually modify some subjective effects of benzodiazepines, potentially altering the time to peak plasma levels but not creating dangerous interactions 5

Important Monitoring Considerations

• When prescribing these medications together, monitor for:
  • Potential changes in the subjective effects of the benzodiazepine, as naltrexone may alter some mood effects 5
  • Standard side effects of each medication independently 1
  • Liver function, as both medications can affect hepatic function 1

Dosing Recommendations

• For naltrexone, the standard dosing for opioid use disorder is typically 50 mg daily 1
• Oxazepam should be prescribed at the lowest effective dose to minimize sedation 1
• When initiating therapy with both medications, consider starting with lower doses and titrating as needed to minimize side effects 1

Important Distinctions and Cautions

• It's crucial to distinguish this combination (opioid antagonist + benzodiazepine) from the dangerous combination of opioid agonists with benzodiazepines, which carries a black box warning due to risk of severe respiratory depression and death 1, 4
• The FDA has issued warnings against combining opioid agonists with benzodiazepines, as this combination increases the risk of death 3-10 fold compared to opioids alone 1
• Naltrexone should be held for 2-3 days prior to elective surgical procedures if opioids are expected to be used perioperatively, as it will block the analgesic effects of opioids 1

Clinical Applications

• This combination may be particularly useful in patients with:
  • Alcohol use disorder who also require treatment for anxiety 1, 2
  • Opioid use disorder in recovery who have comorbid anxiety disorders 2
  • Patients using low-dose naltrexone for pain or autoimmune conditions who require benzodiazepines for anxiety 3

In conclusion, while caution should be exercised when combining any medications, the combination of naltrexone and oxazepam does not present the same risks as combining opioid agonists with benzodiazepines and can be prescribed together when clinically indicated.