Drug interactions
Diphenhydramine + Fentanyl transmucosal
Severity: Major
Diphenhydramine and Fentanyl transmucosal: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Transmucosal fentanyl acts rapidly, and diphenhydramine adds sedation, which increases the risk of respiratory depression. Anticholinergic effects may add to constipation and urinary retention.
What this interaction means in plain words
Diphenhydramine and Fentanyl transmucosal can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Why it happens
Additive CNS and respiratory depression from mu-opioid agonism and H1 blockade, plus additive anticholinergic effects.
What to do
Use the lowest effective doses and monitor sedation and respiratory rate, especially at initiation. Monitor for constipation and urinary retention.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Fentanyl transmucosal?
MediHelp rates the interaction as major. Diphenhydramine and Fentanyl transmucosal can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Transmucosal fentanyl acts rapidly, and diphenhydramine adds sedation, which increases the risk of respiratory depression. Anticholinergic effects may add to constipation and urinary retention.
How serious is the interaction between Diphenhydramine and Fentanyl transmucosal?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use the lowest effective doses and monitor sedation and respiratory rate, especially at initiation. Monitor for constipation and urinary retention.
What other medicines interact with Diphenhydramine?
MediHelp also lists interactions of Diphenhydramine with, for example, Alfentanil, Belladonna and opium, Benzhydrocodone / acetaminophen. The full list is on the Diphenhydramine page.
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