Drug Interaction Report

Ondansetron and Hydromorphone Injection: Interaction Details

A pharmacist-reviewed analysis of the Ondansetron and Hydromorphone Injection 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

Ondansetron

No brand names on record
+

Hydromorphone Injection

Dilaudid Dilaudid-HP® Dilaudid®
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 84 documented Ondansetron interactions, 81 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

Increased risk of serotonin syndrome

Interaction Deep Dive

Concomitant use of opioids, such as HYDROmorphone, with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Discontinue HYDROmorphone if serotonin syndrome is suspected. Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs312.

Why it happens (mechanism)

Additive serotonergic effects

Literature reports

1 report — tap to read

a) Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs 321.

Common questions

Can I take Ondansetron and Hydromorphone Injection together?

Increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ondansetron and Hydromorphone Injection 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 Ondansetron or Hydromorphone 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 (3)

  1. Product Information: DILAUDID(R) oral tablets, oral solution, hydromorphone HCl oral tablets, oral solution. Rhodes Pharmaceuticals LP (per FDA), Wilson, NC, 2023. DailyMed
  2. Product Information: DILAUDID(R) intravenous injection, intramuscular injection, subcutaneous injection, hydromorphone HCl intravenous injection, intramuscular injection, subcutaneous injection. Fresenius Kabi. (per FDA), Lake Zurich, IL, 2023. DailyMed
  3. Product Information: EXALGO(R) oral extended-release tablets, hydromorphone HCl oral extended-release tablets. SpecGx LLC (per FDA), Webster Groves, MO, 2019. DailyMed
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Ondansetron

Keep reading about Ondansetron

All Ondansetron interactions (84)
Also serious with: Ketoconazole Topical Palonosetron Injection Capmatinib Morphine Injection
Hydromorphone Injection

Keep reading about Hydromorphone Injection

All Hydromorphone Injection interactions (344) Hydromorphone Injection drug information
Also serious with: Isocarboxazid Naltrexone Phenelzine Safinamide
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:

Ondansetron + Activated Charcoal Grapefruit Lithium St. John's Wort 1,3-dmaa 5-htp Acacia Rigidula Acetyl-l-carnitine + 187 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.