Hydrocodone and chlorpheniramine and Topiramate interaction

Hydrocodone and chlorpheniramine 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 chlorpheniramine (Hydrocodone Polistirex and Chlorpheniramine Polistirex extended-release) label · effective 2025-06-26

Major

…ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION;…

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 concentration.

Boxed warningby drug classView label on DailyMed
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

Avoid the use of Hydrocodone Polistirex and Chlorpheniramine Polistirex in patients taking benzodiazepines, other CNS depressants, or alcohol [ see Warning and Precautions (5.8) , Drug Interactions (7.5) ].

Boxed warningby drug classView label on DailyMed
Major

Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of hydrocodone.

Boxed warningby drug classView label on DailyMed

From the Topiramate label · effective 2026-05-15

Moderate

Caution should be used when topiramate extended-release capsules are prescribed with other drugs that predispose patients to heat-related disorders; these drugs include, but are not limited to, other carbonic anhydrase inhibitors and drugs with anticholinergic activity.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, topiramate extended-release capsules should be used with extreme caution if used in combination with alcohol and other CNS depressants.

Drug interactionsby drug classView label on DailyMed
Minor

CNS Depressants Concomitant administration of topiramate and alcohol or other CNS depressant drugs 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.