Cenobamate and Hydrocodone and acetaminophen interaction

Cenobamate and Hydrocodone and acetaminophen: 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 Hydrocodone and acetaminophen (Hydrocodone Bitartrate and Acetaminophen) label · effective 2026-05-13

Major

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of hydrocodone bitartrate and acetaminophen tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see WARNINGS ; PRECAUTIONS, Drug Interactions ] .

Boxed warningby drug classView label on DailyMed
Major

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and acetaminophen tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

Boxed warningby drug classView label on DailyMed
Major

In addition, discontinuation of a concomitantly used Cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentrations.

Boxed warningby drug classView label on DailyMed
Major

Monitor patients receiving hydrocodone bitartrate and acetaminophen tablets and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [see CLINICAL PHARMACOLOGY ; WARNINGS ; PRECAUTIONS, Drug Interactions ].

Boxed warningby 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.