Drug interactions
Diphenhydramine + Orphenadrine
Severity: Moderate
Diphenhydramine and Orphenadrine: 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
Both drugs are sedating and anticholinergic, so combined use can cause marked dry mouth, urinary retention, constipation, tachycardia, confusion and drowsiness. Older adults are at particular risk of delirium and falls.
What this interaction means in plain words
Diphenhydramine and Orphenadrine 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.
Why it happens
Additive antimuscarinic and CNS depressant effects.
What to do
Avoid the combination in older adults and monitor for anticholinergic toxicity in others. Choose a non-anticholinergic alternative if 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?
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Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Orphenadrine?
MediHelp rates the interaction as moderate. Diphenhydramine and Orphenadrine 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. Both drugs are sedating and anticholinergic, so combined use can cause marked dry mouth, urinary retention, constipation, tachycardia, confusion and drowsiness. Older adults are at particular risk of delirium and falls.
How serious is the interaction between Diphenhydramine and Orphenadrine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination in older adults and monitor for anticholinergic toxicity in others. Choose a non-anticholinergic alternative if 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.
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