Diphenhydramine and Propofol interaction

Diphenhydramine and Propofol: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Diphenhydramine label · effective 2026-03-05

Major

Use as a Local Anesthetic Because of the risk of local necrosis, this drug should not be used as a local anesthetic.

Contraindicationsby drug classView label on DailyMed
Moderate

Drug Interactions Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc).

Drug interactionsby drug classView label on DailyMed

From the Propofol (Diprivan) label · effective 2025-09-10

Moderate

The intravenous administration of anticholinergic agents (e.g., atropine or glycopyrrolate) should be considered to modify potential increases in vagal tone due to concomitant agents (e.g., succinylcholine) or surgical stimuli.

Warnings and precautionsby drug classView label on DailyMed
Moderate

As with other sedative medications, there is wide interpatient variability in DIPRIVAN dosage requirements, and these requirements may change with time.

Warnings and precautionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.