Drug interactions
Diphenhydramine + Diphenoxylate
Severity: Moderate
Diphenhydramine and Diphenoxylate: 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
Diphenoxylate is an opioid antidiarrheal, usually combined with atropine, and it can cause sedation, particularly at higher doses. Diphenhydramine adds sedative and anticholinergic effects, and together these may increase drowsiness, constipation and urinary retention. Small children are especially sensitive to the opioid effect.
What this interaction means in plain words
Diphenhydramine and Diphenoxylate 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; Diphenoxylate belongs to Gastrointestinal Tract.
Why it happens
Additive central nervous system depression and additive anticholinergic effects.
What to do
Monitor for oversedation and signs of anticholinergic toxicity, and avoid exceeding the recommended dose. Use particular care in children and older adults.
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 Diphenhydramine and Diphenoxylate, 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 Diphenoxylate
Frequently asked questions
Can I take Diphenhydramine with Diphenoxylate?
MediHelp rates the interaction as moderate. Diphenhydramine and Diphenoxylate 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. Diphenoxylate is an opioid antidiarrheal, usually combined with atropine, and it can cause sedation, particularly at higher doses. Diphenhydramine adds sedative and anticholinergic effects, and together these may increase drowsiness, constipation and urinary retention. Small children are especially sensitive to the opioid effect.
How serious is the interaction between Diphenhydramine and Diphenoxylate?
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 oversedation and signs of anticholinergic toxicity, and avoid exceeding the recommended dose. Use particular care in children and older adults.
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.
