Waiting Period After Stopping Naltrexone Before Starting Suboxone
For oral naltrexone, wait 2-3 days after the last dose before initiating Suboxone (buprenorphine/naloxone). For extended-release naltrexone injections, wait 24-30 days before starting buprenorphine therapy.
Oral Naltrexone Washout Period
The standard waiting period is 2-3 days after discontinuing oral naltrexone before starting buprenorphine. This timeframe is based on the pharmacokinetics of naltrexone and its active metabolite 1.
Pharmacologic Rationale
- Naltrexone has a plasma half-life of only 4 hours, but its active metabolite (6-β-naltrexol) has a half-life of 13 hours 1, 2
- The metabolite accumulates during long-term therapy, and antagonist effects persist for 2-3 days after stopping 1
- This 2-3 day washout period allows sufficient clearance of opioid receptor blockade to permit buprenorphine binding 2
Clinical Application
The 2-3 day waiting period is supported by consensus guidelines from the Society for Perioperative Assessment and Quality Improvement (SPAQI), which recommend holding oral naltrexone for 2-3 days before procedures requiring opioid administration 1. This same principle applies when transitioning to buprenorphine, as buprenorphine is a partial mu-opioid agonist that requires available receptor sites to bind effectively.
Extended-Release Naltrexone Washout Period
For extended-release naltrexone injections (Vivitrol), a much longer waiting period of 24-30 days after the last injection is required before starting Suboxone 1, 2.
Why the Extended Wait?
- Extended-release formulations provide sustained naltrexone levels for approximately one month 1
- Receptor upregulation may occur with long-term extended-release naltrexone therapy, potentially requiring even longer washout periods 1
- Starting buprenorphine too early after extended-release naltrexone can result in inadequate therapeutic effect due to persistent receptor blockade 2
Critical Clinical Considerations
Precipitated Withdrawal Risk
Starting buprenorphine while naltrexone is still blocking opioid receptors will not precipitate withdrawal in the traditional sense (since naltrexone is already an antagonist), but it will prevent buprenorphine from providing its therapeutic effects, potentially leaving the patient vulnerable to relapse 2.
Monitoring During Transition
- Patients transitioning from naltrexone to buprenorphine require close monitoring during the washout period 3
- The patient must be opioid-free during this transition to avoid precipitated withdrawal when buprenorphine is eventually initiated 4
- Withdrawal symptoms during the naltrexone washout period may require symptomatic management with clonidine, antiemetics, or other supportive medications 5
Reverse Transition Considerations
Research demonstrates that when transitioning in the opposite direction (from buprenorphine to naltrexone), withdrawal patterns differ significantly, with peak withdrawal occurring around day 5 when naltrexone is started during buprenorphine taper 3, 5. However, when properly managed with overlapping therapy, naltrexone can be started as early as day 2 of buprenorphine taper with acceptable withdrawal symptoms 5.
Common Pitfalls to Avoid
- Do not start buprenorphine too early after extended-release naltrexone—the 24-30 day waiting period is essential and cannot be shortened 1, 2
- Do not assume oral naltrexone clears quickly just because its half-life is short—the active metabolite accumulation requires the full 2-3 day washout 1, 2
- Do not fail to provide supportive care during the transition period, as patients may experience cravings or mild withdrawal symptoms while waiting to start buprenorphine 3