Alfentanil and Diphenhydramine Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diphenhydramine Topical
Alfentanil
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
An increased risk of respiratory and CNS depression and an increased risk of paralytic ileus
Interaction Deep Dive
Reserve concomitant use of ALfentanil with other CNS depressants to clinical settings where alternative treatment options are inadequate. If combination therapy is required, reduce the initial dose of the newly prescribed medication and titrate to clinical response while monitoring for respiratory depression and sedation1. Vasodilation and hypotension caused by concomitant use may delay recovery. If hypotension occurs consider hypovolemia as a cause and manage with parenteral fluids. Consider repositioning the patient to improve venous return to the heart, however, use caution moving the patient due to risk of orthostatic hypotension. If hypotension is not adequately corrected with fluids, consider pressor agents other than EPINEPHrine. Following ALfentanil administration, reduce the dose of other CNS depressants. If the decision is made to manage postoperative pain with ALfentanil concomitantly with or other CNS depressant, start dosing with the lowest effective dosage and titrate based on clinical response. Additionally, concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility 2.
Why it happens (mechanism)
Additive CNS depression; additive effects on gastric motility
Common questions
Can I take Alfentanil and Diphenhydramine Topical together?
An increased risk of respiratory and CNS depression and an increased risk of paralytic ileus Always confirm with your pharmacist or prescriber before making any change.
How serious is the Alfentanil 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 Alfentanil 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)
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
- Product Information: Alfentanil HCl intravenous injection, alfentanil HCl intravenous injection. Rising Pharma Holdings, Inc (per FDA), East Brunswick, NJ, 2025.
Keep reading about Diphenhydramine Topical
Keep reading about Alfentanil
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