Drug interactions
Diphenhydramine + Physostigmine
Severity: Moderate
Diphenhydramine and Physostigmine: 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
Physostigmine increases acetylcholine levels and is used to reverse anticholinergic toxicity, including that from diphenhydramine overdose. The two drugs have opposing effects, and the antihistamine may reduce the cholinergic effect.
What this interaction means in plain words
Diphenhydramine and Physostigmine 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.
Why it happens
Pharmacodynamic antagonism between a cholinesterase inhibitor and a muscarinic antagonist.
What to do
When physostigmine is used deliberately for diphenhydramine toxicity, give it under monitored conditions with atropine available, as cholinergic crisis, seizures and bradycardia can occur. Otherwise avoid routine co-use.
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 Diphenhydramine
Frequently asked questions
Can I take Diphenhydramine with Physostigmine?
MediHelp rates the interaction as moderate. Diphenhydramine and Physostigmine 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. Physostigmine increases acetylcholine levels and is used to reverse anticholinergic toxicity, including that from diphenhydramine overdose. The two drugs have opposing effects, and the antihistamine may reduce the cholinergic effect.
How serious is the interaction between Diphenhydramine and Physostigmine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: When physostigmine is used deliberately for diphenhydramine toxicity, give it under monitored conditions with atropine available, as cholinergic crisis, seizures and bradycardia can occur. Otherwise avoid routine co-use.
What other medicines interact with Diphenhydramine?
MediHelp also lists interactions of Diphenhydramine with, for example, Alfentanil, Belladonna and opium, Benzhydrocodone / acetaminophen. The full list is on the Diphenhydramine page.
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