Drug Interaction Report

Nalbuphine Injection and Trazodone: Interaction Details

A pharmacist-reviewed analysis of the Nalbuphine Injection and Trazodone interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Trazodone

Raldesy
+

Nalbuphine Injection

Nubain®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 257 documented Nalbuphine Injection interactions, 244 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
theoretical
Severity
Major

What happens

An increased risk of serotonin syndrome and an increased risk of CNS depression

Interaction Deep Dive

TraZODone is a serotonergic drug known to cause sedation. Concomitant use of traZODone with another serotonergic drug associated with CNS depression may potentiate each others sedative effects, may result in serotonin syndrome, or both. Signs and symptoms of potentially life-threatening serotonin syndrome may include mental status changes (eg, agitation, hallucinations, delirium, coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms such as nausea, vomiting, or diarrhea. If coadministration is required, monitor all patients for serotonin syndrome, especially during initiation. Notify patients of the increased risk of serotonin syndrome and additive sedation. Immediately discontinue treatment with traZODone and any concomitant serotonergic agent if symptoms of serotonin syndrome occur and initiate supportive treatment12. Counsel the patients that traZODone may enhance the response to CNS depressants 1.

Why it happens (mechanism)

Additive serotonergic effects; additive CNS depression

Common questions

Can I take Nalbuphine Injection and Trazodone together?

An increased risk of serotonin syndrome and an increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.

How serious is the Nalbuphine Injection and Trazodone 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.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Nalbuphine Injection or Trazodone 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 (2)

  1. Product Information: Trazodone HCl oral tablets, trazodone HCl oral tablets. Rising Pharma Holdings, Inc (per DailyMed), East Brunswick, NJ, 2025. DailyMed
  2. Product Information: DESYREL(R) oral tablets, trazodone HCl oral tablets. Fera Pharmaceuticals LLC (per FDA), Locust Valley, NY, 2018.
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Trazodone

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Nalbuphine Injection

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All Nalbuphine Injection interactions (257) Nalbuphine Injection drug information
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Trazodone + Activated Charcoal Beer Grapefruit Lithium Siberian Cocklebur St. John's Wort Wine 1,3-dmaa + 189 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.