Buprenorphine and Naltrexone: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Naltrexone
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Buprenorphine and naltrexone should not be used together. Buprenorphine is an opioid that eases pain or treats opioid dependence by acting on opioid receptors in your body. Naltrexone does the opposite. It blocks those same receptors. When they compete, naltrexone can push the opioid off and set off sudden opioid withdrawal, sometimes within minutes. That can mean fast, intense sweating, nausea, cramps, chills, and feeling very unwell.
Naltrexone also blocks the pain relief buprenorphine would give. The good news is your care team can plan this safely. Please do not start, stop, or change either medicine on your own. Talk with your pharmacist or doctor first so they can guide the timing.
Contraindicated. Naltrexone is a competitive opioid receptor antagonist; buprenorphine is a partial agonist. Concurrent use produces antagonism at mu-opioid receptors, precipitating acute withdrawal (onset within minutes) and abolishing analgesia. Neither is a prodrug; this is a pharmacodynamic, not metabolic, interaction. Evidence is probable.
- Patients must be opioid-free (including tramadol) for at least 7 to 10 days before starting naltrexone; up to 2 weeks may be needed after buprenorphine or methadone.
- A naloxone challenge test can confirm the opioid-free state before naltrexone induction.
- Attempting to override the blockade with high opioid doses risks fatal overdose.
- Naltrexone also blunts opioid antitussives/antidiarrheals.
What happens
Precipitation of opioid withdrawal symptoms; decreased opioid effectiveness
Interaction Deep Dive
Giving naltrexone together with opioids is contraindicated12. In individuals who are dependent, naltrexone reverses the action of narcotic analgesics, producing withdrawal symptoms within 5 minutes of taking it 6. Before starting naltrexone or products that contain naltrexone, such as bupropion/naltrexone, patients must be free of opioids (traMADol included) for at least 7 to 10 days; for those who had previously used methadone or buprenorphine, as long as 2 weeks may be needed 42. Even with proper initiation of naltrexone therapy, extremely high opiate doses can override the blockade, which creates a risk of fatal overdose in patients who try to overcome the blockade on their own 1. The combined product morphine sulfate/naltrexone hydrochloride is indicated for the treatment of moderate to severe pain as directed 3.
Why it happens (mechanism)
Competitive binding at opioid receptors
How to manage this interaction
These two are not combined. Your care team manages this mainly through timing and confirmation, not dose adjustment.
- Before naltrexone is started, you generally need to be opioid-free (including tramadol) for at least 7 to 10 days; up to about 2 weeks may be needed if you were taking buprenorphine or methadone.
- Your team may use a naloxone challenge test to confirm no opioids are on board before beginning naltrexone.
Keep taking your medicines exactly as prescribed and never try to overcome the block with extra opioids, which can be deadly. Ask your pharmacist or prescriber before any change so the switch is timed safely.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A patient with painful peripheral neuropathy showed marked improvement following the addition of oral naltrexone. A 61-year-old man with diabetes reported pain and paresthesias affecting his feet, lower legs, and fingers. His finger stick glucose readings were around 250. He was receiving methadone 80 mg/day along with oxycodone 5 mg four times daily for breakthrough pain. One week prior to presentation, both drugs had been cut by 50% because of concerns regarding medication-seeking behavior. During the subsequent several months he had many dose adjustments, but the pain kept recurring. He also reported nausea. At eight months after presentation, he was on methadone 60 mg four times daily and methylphenidate 30 mg twice daily to counter opioid-induced sedation. "Ultra-low" dose naltrexone was started at 1 mcg twice daily. The patient noted improvement within 1 day. His pain lessened considerably and the chronic nausea went away. The methadone dose was lowered to 50 mg four times daily while the methylphenidate dose was left unchanged. One month later the patient still had the same level of pain relief. The identical methadone dose and 50% of the short-acting opioid were maintained 5.
Common questions
Can I take Buprenorphine and Naltrexone together?
Buprenorphine and naltrexone should not be taken together, because naltrexone blocks opioid receptors and can trigger sudden withdrawal and remove pain relief; you must be opioid-free for 7 to 10 days (up to 2 weeks after buprenorphine) before starting naltrexone, so let your care team manage the timing. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Naltrexone interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Buprenorphine and Naltrexone interaction managed?
These two are not combined. Your care team manages this mainly through timing and confirmation, not dose adjustment. Before naltrexone is started, you generally need to be opioid-free (including tramadol) for at least 7 to 10 days; up to about 2 weeks may be needed if you were taking buprenorphine or methadone. Your team may use a naloxone challenge test to confirm no opioids are on board before b… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Buprenorphine or Naltrexone need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (6)
- Product Information: VIVITROL(R) intramuscular injection extended-release suspension, naltrexone intramuscular injection extended-release suspension. Alkermes, Inc. (per Manufacturer), Waltham, MA, 2013.
- Product Information: REVIA(R) oral tablets, naltrexone HCl oral tablets. Duramed Pharmaceuticals, Inc. (per FDA), Pomona, NY, 2013.
- Product Information: EMBEDA(R) oral extended-release capsules, morphine sulfate and naltrexone hcl oral extended-release capsules. King Pharmaceuticals, Inc. Bristol, TN, 2009. DailyMed
- Product Information: CONTRAVE(R) oral extended-release tablets, naltrexone HCl and bupropion HCl oral extended-release tablets. Orexigen Therapeutics, Inc. (per manufacturer), La Jolla, CA, 2014. DailyMed
- Cruciani RA, Lussier D, Miller-Saultz D, et al: Ultra-low dose oral naltrexone decreases side effects and potentiates the effect of methadone (letter). J Pain Symptom Manage 2003; 25(6):491-494. PubMed
- Tornabene VW: Narcotic withdrawal syndrome caused by naltrexone. Ann Intern Med 1974; 81:785-787. PubMed
Keep reading about Buprenorphine
Keep reading about Naltrexone
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
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