Alprazolam and Tizanidine interaction

Alprazolam 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 Alprazolam (Alprazolam XR) label · effective 2025-02-11

Major

• Effects on Driving and Operating Machinery: Patients receiving • alprazolam XR should be cautioned against operating machinery or driving a motor vehicle, as well as avoiding concomitant use of alcohol and other central nervous system (CNS) depressant drugs.

Warnings and precautionsby drug classView label on DailyMed
Major

Prescribe the lowest effective dosage; avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Effects on Driving and Operating Machinery Because of its CNS depressant effects, patients receiving alprazolam XR should be cautioned against engaging in hazardous occupations or activities requiring complete mental alertness such as operating machinery or driving a motor vehicle.

Warnings and precautionsby drug classView label on DailyMed
Moderate

For the same reason, patients should be cautioned about the concomitant use of alcohol and other CNS depressant drugs during treatment with alprazolam XR [see Drug Interactions (7.1) ] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

• Use with Other CNS Depressants: Produces additive CNS depressant effects.

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

The CNS depressant effects of Zanaflex with alcohol and other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants) may be additive [see Drug Interactions ( 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

Concomitant use of Zanaflex with CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants) may cause additive CNS depressant effects, including sedation.

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.