Hydroxyzine and Tizanidine interaction

Hydroxyzine and Tizanidine: 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 Hydroxyzine label · effective 2025-10-31

Major

Rarely, cardiac arrests and death have been reported in association with the combined use of hydroxyzine hydrochloride intramuscularly and other CNS depressants.

Precautionsby drug classView label on DailyMed
Moderate

PRECAUTIONS THE POTENTIATING ACTION OF HYDROXYZINE MUST BE CONSIDERED WHEN THE DRUG IS USED IN CONJUNCTION WITH CENTRAL NERVOUS SYSTEM DEPRESSANTS SUCH AS NARCOTICS, BARBITURATES AND ALCOHOL.

Precautionsby drug classView label on DailyMed
Moderate

Therefore, when central nervous system depressants are administered concomitantly with hydroxyzine their dosage should be reduced up to 50 percent.

Precautionsby 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

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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.