Doxepin and Zolpidem interaction
Doxepin and Zolpidem: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Zolpidem (zolpidem tartrate) label · effective 2025-11-19
The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.
Risk increases with dose and use with other CNS depressants and alcohol.
Postmarketing reports have shown that complex sleep behaviors may occur with Zolpidem Tartrate alone at recommended doses, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants [see Drug Interactions (7.1) ] .
Additive effects occur with concomitant use of other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol), including daytime use [see Drug Interactions (7.1) ] .
The risk of next-day psychomotor impairment is increased if Zolpidem Tartrate is taken with less than a full night of sleep remaining (7 to 8 hours); if higher than the recommended dose is taken; if coadministered with other CNS depressants or alcohol; or coadministered with other drugs that increase the blood levels of zolpidem.
From the Doxepin (Silenor) label · effective 2026-04-21
Potential additive effects when used in combination with CNS depressants or sedating antihistamines.
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.
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) ].
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) ].
Alcohol: Sedative effects may be increased with doxepin.
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Open in the checkerNot 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.