Drug interactions
Cyclobenzaprine + Diphenhydramine
Severity: Moderate
Cyclobenzaprine 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
Both agents are strongly sedating and anticholinergic, so combining them raises the risk of drowsiness, confusion, constipation, urinary retention and tachycardia. Older patients are particularly vulnerable to delirium and falls.
What this interaction means in plain words
Cyclobenzaprine 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.
Cyclobenzaprine belongs to Musculoskeletal; Diphenhydramine belongs to Respiratory.
Why it happens
Additive antimuscarinic and CNS depressant effects.
What to do
Avoid combining in elderly patients; otherwise use the lowest effective doses and monitor for sedation and anticholinergic toxicity.
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 Cyclobenzaprine
- Cyclobenzaprine + Isocarboxazid Contraindicated
- Cyclobenzaprine + Linezolid Contraindicated
- Cyclobenzaprine + Phenelzine Contraindicated
- Cyclobenzaprine + Safinamide Contraindicated
- Cyclobenzaprine + Selegiline Contraindicated
- Cyclobenzaprine + Selegiline transdermal Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Cyclobenzaprine with Diphenhydramine?
MediHelp rates the interaction as moderate. Cyclobenzaprine 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. Both agents are strongly sedating and anticholinergic, so combining them raises the risk of drowsiness, confusion, constipation, urinary retention and tachycardia. Older patients are particularly vulnerable to delirium and falls.
How serious is the interaction between Cyclobenzaprine 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: Avoid combining in elderly patients; otherwise use the lowest effective doses and monitor for sedation and anticholinergic toxicity.
What other medicines interact with Cyclobenzaprine?
MediHelp also lists interactions of Cyclobenzaprine with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Cyclobenzaprine page.
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