How long should naltrexone be discontinued before initiating oxycodone for pain, and what is the recommended starting dose and titration schedule?

Naltrexone to Oxycodone Transition for Pain Management

Discontinuation Timeline

Oral naltrexone must be discontinued for 3-4 days before initiating oxycodone, while extended-release naltrexone (Vivitrol) requires 24-30 days after the last injection. 1

• The washout period allows opioid receptors to become available for analgesic medications, as naltrexone's active metabolite (6-β-naltrexol) has a 13-hour half-life with antagonist effects persisting 2-3 days after oral administration 1
• For patients on extended-release naltrexone, the 24-30 day waiting period is mandatory because the depot formulation provides sustained receptor blockade that cannot be overcome by standard opioid doses 1, 2
• Attempting to use oxycodone before adequate naltrexone clearance results in complete blockade of analgesic effects and potential precipitation of withdrawal if any residual opioids are present 1

Oxycodone Initiation Protocol

Start with standard immediate-release oxycodone 5-10 mg every 4-6 hours as needed after the appropriate naltrexone washout period. 1

Starting Dose Considerations

• Begin with the lowest effective dose (5 mg) in opioid-naive patients or those with prolonged abstinence, as naltrexone discontinuation creates markedly increased risk of opioid overdose due to loss of tolerance 1, 2
• Patients previously on naltrexone have decreased opioid tolerance and heightened sensitivity to respiratory depression, requiring conservative initial dosing 2
• Provide naloxone rescue kits and overdose education to all patients transitioning from naltrexone to opioids, as this population faces life-threatening overdose risk 1

Titration Schedule

• Increase by 25-50% of the current dose every 1-2 days based on pain response and tolerability, monitoring closely for oversedation 1
• Expect to require 2-4 times typical opioid requirements compared to opioid-tolerant patients, but start conservatively due to zero tolerance after naltrexone 1
• Reassess pain control and side effects at each dose adjustment, using validated pain scales to guide titration 1

Critical Safety Warnings

Never administer oxycodone and naltrexone concomitantly—this combination precipitates severe, potentially life-threatening withdrawal and completely blocks opioid analgesia. 1

• Concomitant use results in pharmacological antagonism where naltrexone competitively blocks mu-opioid receptors, rendering oxycodone completely ineffective for pain relief 1
• If both medications are inadvertently ordered simultaneously, immediately discontinue naltrexone and wait the full washout period before starting oxycodone 1
• Administering naltrexone to patients with recent opioid exposure can precipitate withdrawal requiring hospitalization 1

Verification Before Oxycodone Initiation

Confirm the patient has been completely opioid-free for at least 7-10 days before the naltrexone was started, and document the exact date and formulation of the last naltrexone dose. 1

• Use naloxone challenge testing (observe for 30 minutes after naloxone administration) to confirm adequate opioid clearance if there is any uncertainty about the timeline 1
• Apply validated opioid-withdrawal scales to ensure the patient is not experiencing withdrawal before initiating oxycodone 1
• Document in the medical record: last naltrexone dose date, formulation (oral vs. extended-release), route, and calculated clearance date 1

Alternative Pain Management During Washout

Maximize non-opioid multimodal analgesia during the naltrexone washout period, including NSAIDs, acetaminophen, gabapentinoids, regional anesthesia techniques, and ketamine when appropriate. 1, 3

• Regional nerve blocks and local anesthetic infiltration provide effective analgesia without opioid receptor involvement 3
• Adjunctive medications (gabapentin, pregabalin, ketamine, dexmedetomidine) reduce overall opioid requirements once oxycodone is initiated 3
• Avoid attempting to "override" naltrexone blockade with high-dose opioids—this strategy is ineffective and dangerous 1

Common Pitfalls to Avoid

• Do not shorten the washout period based on symptom resolution or patient request—receptor availability depends on pharmacokinetic clearance, not clinical symptoms 1
• Do not assume oral and extended-release naltrexone have the same washout times—the 24-30 day requirement for Vivitrol is absolute 1, 2
• Do not fail to educate patients about overdose risk after naltrexone discontinuation—this is the highest-risk period for fatal overdose 1, 2
• Do not use oxycodone in patients requiring ongoing naltrexone for opioid use disorder—naltrexone blocks all opioid analgesic effects and alternative pain strategies are mandatory 2