Drug interactions
Diphenhydramine + Mexiletine
Severity: Moderate
Diphenhydramine and Mexiletine: 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 mexiletine levels, increasing the chance of dose-related adverse effects. Additive CNS effects such as dizziness and sedation may also occur.
What this interaction means in plain words
Diphenhydramine and Mexiletine 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; Mexiletine belongs to Cardiovascular.
Why it happens
CYP2D6 inhibition by diphenhydramine reduces mexiletine metabolism.
What to do
Monitor for dizziness, tremor and GI symptoms; consider a non-sedating antihistamine if needed.
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 Mexiletine
- Fezolinetant + Mexiletine Contraindicated
- Mexiletine + Pimozide Contraindicated
- Alosetron + Mexiletine Major
- Amiodarone + Mexiletine Major
- Clozapine + Mexiletine Major
- Cobicistat + Mexiletine Major
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Mexiletine?
MediHelp rates the interaction as moderate. Diphenhydramine and Mexiletine 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 mexiletine levels, increasing the chance of dose-related adverse effects. Additive CNS effects such as dizziness and sedation may also occur.
How serious is the interaction between Diphenhydramine and Mexiletine?
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 dizziness, tremor and GI symptoms; consider a non-sedating antihistamine if needed.
What other medicines interact with Mexiletine?
MediHelp also lists interactions of Mexiletine with, for example, Fezolinetant, Pimozide, Alosetron. The full list is on the Mexiletine page.
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