Drug interactions
Diphenhydramine + Nortriptyline
Severity: Moderate
Diphenhydramine and Nortriptyline: 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 inhibits CYP2D6 and may raise nortriptyline concentrations, while both drugs are sedating and strongly anticholinergic. The result can be excess sedation, confusion, urinary retention, constipation and arrhythmia risk, especially in older adults.
What this interaction means in plain words
Diphenhydramine and Nortriptyline 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; Nortriptyline belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by diphenhydramine plus additive antimuscarinic and sedative effects.
What to do
Avoid regular concurrent use in older patients and choose a non-sedating antihistamine if needed. Monitor for anticholinergic toxicity and consider checking nortriptyline levels.
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 Nortriptyline
- Disopyramide + Nortriptyline Contraindicated
- Dofetilide + Nortriptyline Contraindicated
- Dronedarone + Nortriptyline Contraindicated
- Ibutilide + Nortriptyline Contraindicated
- Isocarboxazid + Nortriptyline Contraindicated
- Methylene blue + Nortriptyline Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Nortriptyline?
MediHelp rates the interaction as moderate. Diphenhydramine and Nortriptyline 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 inhibits CYP2D6 and may raise nortriptyline concentrations, while both drugs are sedating and strongly anticholinergic. The result can be excess sedation, confusion, urinary retention, constipation and arrhythmia risk, especially in older adults.
How serious is the interaction between Diphenhydramine and Nortriptyline?
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 regular concurrent use in older patients and choose a non-sedating antihistamine if needed. Monitor for anticholinergic toxicity and consider checking nortriptyline levels.
What other medicines interact with Nortriptyline?
MediHelp also lists interactions of Nortriptyline with, for example, Disopyramide, Dofetilide, Dronedarone. The full list is on the Nortriptyline page.
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