Diphenhydramine Topical and Ketamine: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diphenhydramine Topical
Ketamine
No brand names on record
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 respiratory and CNS depression
Interaction Deep Dive
Concomitant administration of ketamine and opioid analgesics, benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. If used concomitantly, closely monitor neurological status and respiratory parameters, including respiratory rate and pulse oximetry. Consider dose adjustments individualized to the patient's clinical situation1.
Why it happens (mechanism)
Additive CNS depression
Common questions
Can I take Diphenhydramine Topical and Ketamine together?
Increased risk of respiratory and CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diphenhydramine Topical and Ketamine 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 Diphenhydramine Topical or Ketamine 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: KETALAR(R) intravenous, intramuscular injection, ketamine HCl intravenous, intramuscular injection. Par Pharmaceutical (per FDA), Chestnut Ridge, NY, 2020. DailyMed
Keep reading about Diphenhydramine Topical
Keep reading about Ketamine
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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