Hydrocodone and acetaminophen and Topiramate interaction

Hydrocodone and acetaminophen and Topiramate: 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

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

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of hydrocodone bitartrate and acetaminophen tablets with benzodiazepines and/or other CNS depressants, including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers,…

Warningsby drug classView label on DailyMed
Major

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see PRECAUTIONS, Drug Interactions , Information for Patients/Caregivers ].

Warningsby drug classView label on DailyMed

From the Topiramate (Trokendi XR) label · effective 2026-03-20

Moderate

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, TROKENDI XR should be used with extreme caution if used in combination with alcohol and other CNS depressants [see Contraindications (4) and Warnings and Precautions (5.7) ].

Drug interactionsby drug classView label on DailyMed
Minor

CNS Depressants Concomitant administration of topiramate with other CNS depressant drugs or alcohol has not been evaluated in clinical studies.

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.