Remifentanil 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
Remifentanil
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 CNS depression and an increased risk of hypotension
Interaction Deep Dive
Concomitant use of remifentanil with CNS depressants can lead to hypotension, sedation, respiratory depression, coma, and death. Reserve concomitant use of remifentanil or other CNS depressants for patients for whom alternative treatment options are inadequate. If concomitant use is required, administer the lowest effective dose of each agent for the shortest duration necessary and monitor for signs of respiratory depression and sedation. Fluids or other measures to counter hypotension should be available1.
Why it happens (mechanism)
Additive CNS depression
Literature reports
1 report — tap to read
a) In a cohort study of data from 2004 to 2009, the risk of fatal overdose significantly increased by 2.33 fold in patients taking opioid analgesics with a history of a benzodiazepine prescription and increased by 3.86 fold in those with a current benzodiazepine prescription compared with those taking opioid analgesics without a history of a benzodiazepine prescription. The risk of drug overdose deaths increased with increasing daily doses of benzodiazepines 2.
Common questions
Can I take Remifentanil and Diphenhydramine Topical together?
Increased risk of CNS depression and an increased risk of hypotension Always confirm with your pharmacist or prescriber before making any change.
How serious is the Remifentanil 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 Remifentanil 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: ULTIVA® intravenous injection, remifentanil HCl intravenous injection. Mylan Institutional LLC (per FDA), Morgantown, WV, 2025. DailyMed
- 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.
Keep reading about Diphenhydramine Topical
Keep reading about Remifentanil
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