Drug Interaction Report

Sufentanil and Diphenhydramine Topical: Interaction Details

Name: Sufentanil and Diphenhydramine Topical Interaction
Creator: Dr. Brian Staiger, PharmD, BCPS

A pharmacist-reviewed analysis of the Sufentanil and Diphenhydramine Topical 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

Diphenhydramine Topical

Afterbite with Antihistamine Benadryl® Itch Stopping Gel Dermamycin

Sufentanil

Dsuvia

Medically reviewed by

Dr. Brian Staiger, PharmD, BCPS

Updated Aug 8, 2026

Editorial policy · Data sources

Interaction severity

Major

Potentially serious — often needs a change or close monitoring.

Minor

Moderate

Major

Contraindicated

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 56 documented Sufentanil interactions, 54 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 for hypotension, profound sedation, respiratory depression, coma, and death, increased risk of urinary retention and/or severe constipation leading to paralytic ileus

Interaction Deep Dive

When using SUFentanil for postoperative analgesia, concomitant use with other CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescription of SUFentanil and benzodiazepines or other CNS depressants in patients for whom alternative treatment options are inadequate. If the decision is made to manage postoperative pain with SUFentanil concomitantly with other CNS depressant, start with a lower dose of SUFentanil and titrate based on clinical response. Monitor patients closely for signs and symptoms of respiratory depression, sedation, and hypotension. Additionally, concomitant use of SUFentanil with anticholinergics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility¹². Concomitant use of SUFentanil injection with CNS depressants may result in decreased pulmonary artery pressure and may cause hypotension. Keep fluids and other measures readily available to treat potential hypotension ¹.

Why it happens (mechanism)

Additive CNS depression; additive effects on gastric motility

Common questions

Can I take Sufentanil and Diphenhydramine Topical together?

Increased risk for hypotension, profound sedation, respiratory depression, coma, and death, increased risk of urinary retention and/or severe constipation leading to paralytic ileus Always confirm with your pharmacist or prescriber before making any change.

How serious is the Sufentanil and Diphenhydramine Topical 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 Sufentanil or Diphenhydramine Topical 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)

Product Information: Sufentanil citrate injection, sufentanil citrate r intravenous and epidural injection. Akron Inc (per FDA), Lake Forest, IL, 2023. DailyMed
Product Information: DSUVIA(TM) sublingual tablets, sufentanil sublingual tablets. AcelRx Pharmaceuticals Inc (per FDA), Hayward, CA, 2023. DailyMed

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Diphenhydramine Topical

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Sufentanil

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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:

Sufentanil + Activated Charcoal Coffee Charcoal European Mandrake Glucomannan Guar Gum Gum Arabic Slippery Elm Tragacanth + 9 more

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

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A message from HelloPharmacist

About our interaction database: depth, not breadth

HelloPharmacist doesn't license one of the big commercial interaction databases, so what you'll find here is not a complete list of every known drug interaction. Instead, each entry is researched, analyzed, and written up individually — documented from the published literature, reviewed by a pharmacist, and cited so you can check every source yourself.

If a combination isn't listed here, it means we haven't documented it yet — never that it's safe. For screening a full medication list, we recommend pairing this site with a comprehensive tool like the Drugs.com Interaction Checker and, most importantly, a review by your own pharmacist. For a deep, plain-English, fully sourced explanation of a specific documented interaction — that's exactly what we built this for.

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.