Drug interactions
Diphenhydramine + Diphenoxylate-atropine
Severity: Moderate
Diphenhydramine and Diphenoxylate-atropine: 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 has strong anticholinergic and sedative properties that add to the atropine content of the antidiarrheal. This can produce dry mouth, blurred vision, urinary retention, constipation, confusion and sedation, particularly in older adults.
What this interaction means in plain words
Diphenhydramine and Diphenoxylate-atropine 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-atropine belongs to Gastrointestinal Tract.
Why it happens
Additive antimuscarinic and sedative effects.
What to do
Monitor for anticholinergic toxicity and sedation and avoid the combination in older patients or those with urinary retention or glaucoma. Choose a non-sedating antihistamine if appropriate.
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 Diphenoxylate-atropine
- Diphenoxylate-atropine + Isocarboxazid Contraindicated
- Diphenoxylate-atropine + Phenelzine Contraindicated
- Diphenoxylate-atropine + Tranylcypromine Contraindicated
- Alfentanil + Diphenoxylate-atropine Major
- Alvimopan + Diphenoxylate-atropine Major
- Amitriptyline + Diphenoxylate-atropine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Diphenoxylate-atropine?
MediHelp rates the interaction as moderate. Diphenhydramine and Diphenoxylate-atropine 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 has strong anticholinergic and sedative properties that add to the atropine content of the antidiarrheal. This can produce dry mouth, blurred vision, urinary retention, constipation, confusion and sedation, particularly in older adults.
How serious is the interaction between Diphenhydramine and Diphenoxylate-atropine?
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 anticholinergic toxicity and sedation and avoid the combination in older patients or those with urinary retention or glaucoma. Choose a non-sedating antihistamine if appropriate.
What other medicines interact with Diphenoxylate-atropine?
MediHelp also lists interactions of Diphenoxylate-atropine with, for example, Isocarboxazid, Phenelzine, Tranylcypromine. The full list is on the Diphenoxylate-atropine page.
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