Drug interactions
Difelikefalin + Diphenhydramine
Severity: Moderate
Difelikefalin and Diphenhydramine: 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
Difelikefalin is a peripherally restricted kappa opioid agonist given to treat uremic itch in dialysis patients. It can cause somnolence and dizziness, and diphenhydramine may add to these effects. Patients on dialysis may also be more sensitive to sedatives.
What this interaction means in plain words
Difelikefalin and Diphenhydramine 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.
Difelikefalin belongs to Dermatology; Diphenhydramine belongs to Respiratory.
Why it happens
Additive central nervous system depression from different mechanisms.
What to do
Monitor for drowsiness, dizziness and falls. Avoid additional sedating antihistamines where possible.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Difelikefalin and Diphenhydramine, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
Other interactions of Diphenhydramine
Other interactions of Difelikefalin
- Acetazolamide + Difelikefalin Moderate
- Alprazolam + Difelikefalin Moderate
- Amantadine + Difelikefalin Moderate
- Amitriptyline + Difelikefalin Moderate
- Amobarbital + Difelikefalin Moderate
- Asenapine + Difelikefalin Moderate
Frequently asked questions
Can I take Difelikefalin with Diphenhydramine?
MediHelp rates the interaction as moderate. Difelikefalin and Diphenhydramine 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. Difelikefalin is a peripherally restricted kappa opioid agonist given to treat uremic itch in dialysis patients. It can cause somnolence and dizziness, and diphenhydramine may add to these effects. Patients on dialysis may also be more sensitive to sedatives.
How serious is the interaction between Difelikefalin and Diphenhydramine?
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 for drowsiness, dizziness and falls. Avoid additional sedating antihistamines where possible.
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.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
