Samidorphan and Nalbuphine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Samidorphan
No brand names on recordNalbuphine 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
Decreased opioid efficacy and precipitation of opioid withdrawal
Interaction Deep Dive
Concomitant use of samidorphan, an opioid antagonist, is contraindicated with an opioid or in those undergoing acute opioid withdrawal as samidorphan increases the risk of precipitating acute opioid withdrawal in patients who are dependent on opioids. Prior to initiating samidorphan, there should be at least a 7-day opioid-free interval from the last use of short-acting opioids, and at least a 14-day opioid-free interval from the last use of long-acting opioids. In an emergency, if a samidorphan-treated patient requires opioid treatment for anesthesia or analgesia, discontinue samidorphan. The opioid should be administered by properly trained individual(s), and the patient should be properly monitored in a setting equipped and staffed for cardiopulmonary resuscitation. In non-emergency setting, if a samidorphan-treated patient is expected to require opioid treatment (eg, for analgesia during or after an elective surgical procedure) discontinue samidorphan at least 5 days before opioid treatment1.
Why it happens (mechanism)
Competitive binding at opioid receptors
Common questions
Can I take Samidorphan and Nalbuphine Injection together?
Decreased opioid efficacy and precipitation of opioid withdrawal Always confirm with your pharmacist or prescriber before making any change.
How serious is the Samidorphan 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 "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Samidorphan 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 (1)
- Product Information: LYBALVI(TM) oral tablets, olanzapine samidorphan oral tablets. Alkermes Inc (per manufacturer), Waltham, MA, 2021. DailyMed
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