How long should one wait after taking benzodiazepines (benzos) to start naltrexone?

Waiting Period Between Benzodiazepines and Naltrexone

After taking benzodiazepines, patients should wait at least 24 hours before starting naltrexone to avoid potential adverse interactions, though this waiting period is primarily related to ensuring benzodiazepines have cleared the system rather than a direct contraindication.

Pharmacological Considerations

Benzodiazepines and naltrexone work on different receptor systems:

• Benzodiazepines: Act on GABA receptors to produce sedative, anxiolytic, and muscle relaxant effects
• Naltrexone: Acts as an opioid receptor antagonist, blocking the effects of opioids

Half-life Considerations

• The plasma half-life of naltrexone is approximately 4 hours
• The half-life of its active metabolite, 6-β-naltrexol, is about 13 hours 1
• Benzodiazepines have varying half-lives:
  • Short-acting: 4-12 hours
  • Intermediate-acting: 12-24 hours
  • Long-acting: >24 hours

Clinical Recommendations

Standard Waiting Period

• Minimum waiting period: 24 hours after the last benzodiazepine dose
• This allows for adequate clearance of most short and intermediate-acting benzodiazepines

Special Considerations

1. Long-acting benzodiazepines: May require longer waiting periods (48-72 hours) due to extended half-lives and active metabolites

2. Patients with liver impairment:

   • Naltrexone AUC increases approximately 5-10 fold in patients with liver cirrhosis 2
   • Benzodiazepine metabolism is also impaired
   • Consider extending the waiting period to 48-72 hours

3. Elderly patients:

   • May have reduced clearance of both medications
   • Consider extending the waiting period to 48 hours

Important Clinical Caveats

• The primary concern when transitioning between these medications is not a direct drug interaction but ensuring:

  1. The patient is not sedated from benzodiazepines when starting naltrexone
  2. The patient's mental status is clear enough to understand naltrexone instructions

• Critical distinction: Unlike the transition from opioids to naltrexone (which requires 7-10 days to avoid precipitated withdrawal 2), there is no risk of precipitated withdrawal when transitioning from benzodiazepines to naltrexone

Patient Monitoring

When initiating naltrexone after benzodiazepine use:

• Monitor for sedation or cognitive impairment
• Assess for signs of benzodiazepine withdrawal if the patient was a chronic user
• Ensure the patient understands that naltrexone will block the effects of any opioids

Risk Mitigation

• If the patient has been on long-term benzodiazepine therapy, consider a gradual taper before initiating naltrexone rather than abrupt discontinuation
• For patients with a history of substance use disorders, close monitoring during this transition period is essential

Remember that while there is no direct contraindication between these medications, ensuring proper clearance of benzodiazepines before starting naltrexone optimizes safety and effectiveness of treatment.