Drug interactions
Diphenhydramine + Thioridazine
Severity: Major
Diphenhydramine and Thioridazine: major interaction.
Last updated Sources: UK SmPC
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 thioridazine concentrations, and thioridazine has dose-related QT prolongation. Additive anticholinergic and sedative effects also occur.
What this interaction means in plain words
Diphenhydramine and Thioridazine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Diphenhydramine belongs to Respiratory; Thioridazine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by diphenhydramine reduces thioridazine metabolism, plus additive anticholinergic and CNS depressant effects.
What to do
Avoid the combination and choose a non-sedating antihistamine such as loratadine. If used, monitor ECG and anticholinergic effects.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Thioridazine
- Abiraterone + Thioridazine Contraindicated
- Adagrasib + Thioridazine Contraindicated
- Amiodarone + Thioridazine Contraindicated
- Amisulpride + Thioridazine Contraindicated
- Amitriptyline + Thioridazine Contraindicated
- Amoxapine + Thioridazine Contraindicated
Other interactions of Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Thioridazine?
MediHelp rates the interaction as major. Diphenhydramine and Thioridazine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Diphenhydramine inhibits CYP2D6 and may raise thioridazine concentrations, and thioridazine has dose-related QT prolongation. Additive anticholinergic and sedative effects also occur.
How serious is the interaction between Diphenhydramine and Thioridazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid the combination and choose a non-sedating antihistamine such as loratadine. If used, monitor ECG and anticholinergic effects.
What other medicines interact with Thioridazine?
MediHelp also lists interactions of Thioridazine with, for example, Abiraterone, Adagrasib, Amiodarone. The full list is on the Thioridazine page.
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