Cenobamate and Zolpidem interaction

Cenobamate 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.

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 Zolpidem (zolpidem tartrate) label · effective 2025-11-19

Major

The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.

Warnings and precautionsby drug classView label on DailyMed
Major

John's wort, a CYP3A4 inducer, in combination with zolpidem may decrease blood levels of zolpidem and is not recommended.

Drug interactionsby drug classView label on DailyMed
Moderate

Risk increases with dose and use with other CNS depressants and alcohol.

Warnings and precautionsby drug classView label on DailyMed
Moderate

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) ] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

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) ] .

Warnings and precautionsby drug classView label on DailyMed

From the Cenobamate (Xcopri) label · effective 2025-08-25

Moderate

Concomitant use with other CNS depressants or alcohol may have additive effects.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence and sedation, when XCOPRI is used with other drugs with sedative properties because of potential additive effects.

Warnings and precautionsby drug classView label on DailyMed
Moderate

CNS Depressants and Alcohol Concomitant use of XCOPRI with other CNS depressants, including alcohol, may increase the risk of neurological adverse reactions, including sedation and somnolence [see Warnings and Precautions ( 5.5 )] .

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.