Diphenhydramine and Tizanidine interaction

Diphenhydramine and Tizanidine: both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.

Moderate

Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.

What the FDA labels say

From the Diphenhydramine label · effective 2026-03-05

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 Tizanidine (Zanaflex) label · effective 2026-01-02

Moderate

Sedation: Zanaflex may interfere with everyday activities; sedative effects of Zanaflex, alcohol, and other central nervous system (CNS) depressants are additive ( 5.3 , 7.4 )

Warnings and precautionsby drug classView label on DailyMed
Moderate

Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Alcohol and Other CNS Depressants Alcohol increases the exposure of tizanidine after administration of Zanaflex.

Drug interactionsby drug classView label on DailyMed
Moderate

Monitor patients who take Zanaflex with another CNS depressant for symptoms of excess sedation [see Clinical Pharmacology ( 12.3 )] .

Drug interactionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

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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.