Drug interactions
Amitriptyline + Diphenhydramine
Severity: Moderate
Amitriptyline 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 drugs have strong antimuscarinic and sedative properties, so combining them adds to anticholinergic burden and drowsiness. Patients may develop dry mouth, constipation, urinary retention, blurred vision, confusion and impaired psychomotor performance, especially older adults.
What this interaction means in plain words
Amitriptyline 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.
Amitriptyline belongs to Central Nervous System; Diphenhydramine belongs to Respiratory.
Why it happens
Additive muscarinic receptor blockade and additive histamine H1 antagonism in the central nervous system.
What to do
Avoid routine use of diphenhydramine as a sleep aid in patients taking amitriptyline, particularly in the elderly. Monitor for anticholinergic toxicity, sedation and falls, and choose a non-sedating alternative 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?
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Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Amitriptyline with Diphenhydramine?
MediHelp rates the interaction as moderate. Amitriptyline 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 drugs have strong antimuscarinic and sedative properties, so combining them adds to anticholinergic burden and drowsiness. Patients may develop dry mouth, constipation, urinary retention, blurred vision, confusion and impaired psychomotor performance, especially older adults.
How serious is the interaction between Amitriptyline 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 routine use of diphenhydramine as a sleep aid in patients taking amitriptyline, particularly in the elderly. Monitor for anticholinergic toxicity, sedation and falls, and choose a non-sedating alternative where possible.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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