Alprazolam and Doxepin interaction

Alprazolam and Doxepin: 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.

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From the Doxepin (Silenor) label · effective 2026-04-21

Moderate

Potential additive effects when used in combination with CNS depressants or sedating antihistamines.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When taken with SILENOR, the sedative effects of alcoholic beverages, sedating antihistamines, and other CNS depressants may be potentiated [s ee Warnings and Precautions (5.2) and Drug Interactions (7.3 , 7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Patients should be cautioned about potential additive effects of SILENOR used in combination with CNS depressants or sedating antihistamines [s ee Warnings and Precautions (5.2) and Drug Interactions (7.4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Alcohol: Sedative effects may be increased with doxepin.

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.