Alprazolam and Promethazine interaction

Alprazolam and Promethazine: 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
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
Minor

Examples Psychotropic medications, anticonvulsants, antihistaminics, ethanol, and other drugs which themselves produce CNS depression.

Drug interactionsby drug classView label on DailyMed

From the Promethazine (PROMETHAZINE HYDROCHLORIDE) label · effective 2026-04-16

Moderate

The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine…

Warningsby drug classView label on DailyMed
Moderate

Drug Interactions CNS Depressants Promethazine Syrup may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered…

Drug interactionsby drug classView label on DailyMed
Moderate

CNS Depressants Promethazine Syrup may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced…

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.