Drug interactions
Diphenhydramine + Fentanyl
Severity: Moderate
Diphenhydramine and Fentanyl: moderate interaction.
Last updated
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
Diphenhydramine is a sedating anticholinergic antihistamine and adds to the CNS depression of fentanyl. Combined anticholinergic and opioid effects may worsen constipation and urinary retention, especially in older adults.
What this interaction means in plain words
Diphenhydramine and Fentanyl can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Diphenhydramine belongs to Respiratory; Fentanyl belongs to Musculoskeletal.
Why it happens
Additive CNS depression and anticholinergic effects.
What to do
Monitor sedation and respiratory rate, and check for urinary retention and constipation. Use the lowest diphenhydramine dose or a non-sedating antihistamine, particularly in older patients.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Fentanyl
- Alvimopan + Fentanyl Contraindicated
- Fentanyl + Isocarboxazid Contraindicated
- Fentanyl + Olanzapine / samidorphan Contraindicated
- Fentanyl + Phenelzine Contraindicated
- Fentanyl + Tranylcypromine Contraindicated
- Alfentanil + Fentanyl Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Fentanyl?
MediHelp rates the interaction as moderate. Diphenhydramine and Fentanyl can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Diphenhydramine is a sedating anticholinergic antihistamine and adds to the CNS depression of fentanyl. Combined anticholinergic and opioid effects may worsen constipation and urinary retention, especially in older adults.
How serious is the interaction between Diphenhydramine and Fentanyl?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor sedation and respiratory rate, and check for urinary retention and constipation. Use the lowest diphenhydramine dose or a non-sedating antihistamine, particularly in older patients.
What other medicines interact with Fentanyl?
MediHelp also lists interactions of Fentanyl with, for example, Alvimopan, Isocarboxazid, Olanzapine / samidorphan. The full list is on the Fentanyl page.
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