Nalbuphine Injection and Difenoxin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Difenoxin
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
Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression
Interaction Deep Dive
Coadministration of nalbuphine with CNS depressants may result in sedation and respiratory depression. Coadministration of nalbuphine with serotonergic agents including SSRIs, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, 5-HT3 receptor antagonists, drugs that impair serotonin metabolism, and others that affect the serotonergic system, may result in serotonin syndrome. Reserve the concomitant use of nalbuphine and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of nalbuphine or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome1.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
Common questions
Can I take Nalbuphine Injection and Difenoxin together?
Increased risk of serotonin syndrome; increased risk of respiratory and CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Nalbuphine Injection and Difenoxin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Nalbuphine Injection or Difenoxin 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: NUBAIN(R) intramuscular, subcutaneous, intravenous injection, nalbuphine HCl intramuscular, subcutaneous, intravenous injection. Par Pharmaceutical (per FDA), Chestnut Ridge, NY, 2016.
Keep reading about Difenoxin
Keep reading about Nalbuphine Injection
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