Drug Interaction Report

Haloperidol and Esketamine Nasal Spray: Interaction Details

A pharmacist-reviewed analysis of the Haloperidol and Esketamine Nasal Spray 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

Haloperidol

No brand names on record
+

Esketamine Nasal Spray

Spravato Spravato®
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 126 documented Haloperidol interactions, 118 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 haloperidol exposure, an increased risk of haloperidol-related adverse events and an increased risk of CNS depression

Interaction Deep Dive

Concomitant use of esketamine, which is a CNS depressant, with another CNS depressant, such as haloperidol may potentiate each other's effects. Ensure close monitoring for sedation with any concomitant use123. Additionally, coadminister of haloperidol and esketamine (CYP3A4 inhibitor) may increase haloperidol exposure, which may increase haloperidol-related adverse events, including QTc interval prolongation. It is recommended that patients who take haloperidol concomitantly with esketamine be monitored for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol, and haloperidol dose be reduced as deemed necessary 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of haloperidol; additive CNS depression

Common questions

Can I take Haloperidol and Esketamine Nasal Spray together?

Increased haloperidol exposure, an increased risk of haloperidol-related adverse events and an increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.

How serious is the Haloperidol and Esketamine Nasal Spray 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 Haloperidol or Esketamine Nasal Spray 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: SPRAVATO(TM) nasal spray, esketamine nasal spray. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2019. DailyMed
  2. Product Information: HALDOL(R) Decanoate 100 intramuscular injection, haloperidol decanoate intramuscular injection. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2025.
  3. Product Information: Haloperidol oral solution, haloperidol oral solution. Advagen Pharma Ltd. (per DailyMed), East Windsor, NJ, 2024. DailyMed
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Haloperidol

Keep reading about Haloperidol

All Haloperidol interactions (126)
Also serious with: Metoclopramide Injection Ketoconazole Topical Metoclopramide Nasal Spray Cetirizine Injection
Esketamine Nasal Spray

Keep reading about Esketamine Nasal Spray

All Esketamine Nasal Spray interactions (194) Esketamine Nasal Spray drug information
Also serious with: Isocarboxazid Zuranolone Foscarbidopa Fluspirilene
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:

Haloperidol + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Indian Snakeroot Rauvolfia Vomitoria + 203 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.