What happens if someone starts Sublocade (buprenorphine) and a week later takes one dose of naltrexone 50mg?

Severe Precipitated Withdrawal Will Occur if Naltrexone is Taken One Week After Starting Sublocade

Taking naltrexone 50mg one week after starting Sublocade (buprenorphine) will cause severe precipitated withdrawal that may require hospitalization due to the competitive antagonism between these medications.

Mechanism of Interaction

• Naltrexone is a pure opioid antagonist that competitively binds to opioid receptors, blocking the effects of opioids including buprenorphine (Sublocade) 1
• Buprenorphine (Sublocade) is a partial opioid agonist with high affinity for mu-opioid receptors that remains bound to these receptors for extended periods 2
• When naltrexone is introduced while buprenorphine is still present, it displaces buprenorphine from receptors, resulting in abrupt cessation of opioid effects 3

Expected Clinical Presentation

• Severe precipitated withdrawal symptoms will occur within minutes to hours of taking naltrexone 4
• Common symptoms include:
  • Agitation (96.2% of patients) - the most difficult withdrawal symptom to manage 4
  • Altered level of consciousness (38.6%) 4
  • Gastrointestinal distress: nausea (28%), vomiting (27.3%), abdominal pain (24.2%), diarrhea (16.7%) 4
  • Bone and muscle pain (15.9%) 4
  • Tachycardia (12.9%) and dilated pupils (11.4%) 4
• In severe cases, withdrawal can lead to:
  • Dehydration from persistent vomiting and diarrhea 3
  • Cardiovascular complications including arrhythmias 3
  • Potential need for hospitalization 1

Timing Considerations

• Patients must be completely opioid-free before starting naltrexone to avoid precipitation of withdrawal 3
• For oral naltrexone, patients should be off all opioids for a minimum of 7-10 days before starting treatment 3
• Sublocade (extended-release buprenorphine) has a half-life of approximately 43-60 days, making it present in the system for weeks to months after injection 2
• One week after Sublocade administration is far too soon to introduce naltrexone 3, 1

Management of Precipitated Withdrawal

• If precipitated withdrawal occurs, immediate medical attention may be required 1
• Treatment is primarily supportive:
  • IV fluids for dehydration 5
  • Anti-emetics for nausea and vomiting 5
  • Clonidine for autonomic symptoms 6
  • Benzodiazepines for agitation and anxiety 6
• Unlike naloxone-precipitated withdrawal, which is short-lived, naltrexone-precipitated withdrawal can persist for days due to naltrexone's longer half-life (4-13 hours) 1

Prevention Strategies

• Naltrexone should only be started after:
  • Complete discontinuation of Sublocade
  • Waiting a minimum of 7-10 days after the last dose of short-acting opioids 3
  • For Sublocade, this waiting period should be significantly longer (potentially weeks to months) due to its extended-release formulation 2
• A naloxone challenge test can be performed to confirm the absence of physiological opioid dependence before starting naltrexone 1
• Patients should be fully informed about the risks of precipitated withdrawal and the importance of proper timing when transitioning between these medications 1

Special Considerations

• The severity of withdrawal may be influenced by:
  • The dose of Sublocade received 2
  • Individual metabolism and clearance rates 1
  • Prior opioid use history 3
• Precipitated withdrawal from naltrexone is typically more severe than spontaneous withdrawal that occurs with discontinuation of opioids 1