Naltrexone and Nalbuphine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Naltrexone
Nalbuphine Injection
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.
What happens
Precipitation of opioid withdrawal symptoms; decreased opioid effectiveness
Interaction Deep Dive
The concurrent administration of naltrexone and opioids is contraindicated12. Naltrexone will reverse the effects of narcotic analgesics in dependent persons, resulting in withdrawal symptoms within 5 minutes of ingestion 6. Patients should be opioid-free (including traMADol) for a minimum of 7 to 10 days before initiating treatment with naltrexone or naltrexone-containing products such as bupropion/naltrexone; up to 2 weeks may be required for patients previously taking methadone or buprenorphine 42. Even when naltrexone therapy is initiated properly, the blockade can be overcome with very high dosages of opiates, posing the risk of fatal overdose in patients attempting to surmount the blockade on their own 1. The combination substance morphine sulfate/naltrexone hydrochloride is indicated to treat moderate to severe pain as directed 3.
Why it happens (mechanism)
Competitive binding at opioid receptors
Literature reports
1 report — tap to read
a) Significant improvement after the additions of oral naltrexone occurred in a patient with painful peripheral neuropathy. A 61-year-old male patient with diabetes complained of pain and paresthesias in the feet, distal legs, and fingers. His finger stick glucose measurements were in the 250 range. He was taking methadone 80 mg/day and oxycodone 5 mg 4 times daily for breakthrough pain. Both medications were reduced by 50% a week before presentation due to concerns about medication-seeking behavior. Over the next several months he underwent numerous dose adjustments but the pain would return. He also complained of nausea. Eight months after presentation, the patient was taking methadone 60 mg 4 times daily and methylphenidate 30 mg twice daily for opioid-induced sedation. "Ultra-low" dose naltrexone was initiated at 1 mcg twice daily. The patient reported improvement within 1 day. His pain decreased significantly and the chronic nausea resolved. The methadone dose was decreased to 50 mg four times daily and methylphenidate dose remained unchanged. The patient remained with the same degree of pain relief 1 month later. The same dose of methadone and 50% of the short-acting opioid were used 5.
Common questions
Can I take Naltrexone and Nalbuphine Injection together?
Precipitation of opioid withdrawal symptoms; decreased opioid effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Naltrexone and Nalbuphine Injection 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 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 Naltrexone or Nalbuphine Injection 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.
- 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. DOI
Keep reading about Naltrexone
Keep reading about Nalbuphine Injection
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