Hydrocodone and chlorpheniramine and Tramadol and acetaminophen interaction

Hydrocodone and chlorpheniramine and Tramadol 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 Tramadol and acetaminophen (Tramadol Hydrochloride and Acetaminophen) label · effective 2026-01-01

Major

…TRAMADOL HYDROCHLORIDE AND ACETAMINOPHEN TABLETS Addiction, Abuse, and Misuse Because the use of tramadol hydrochloride and acetaminophen exposes patients and other users to the risks of opioid addiction, abuse and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of…

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

Reserve concomitant prescribing of tramadol hydrochloride and acetaminophen and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) and Drug Interactions (7) ] .

Boxed warningby drug classView label on DailyMed
Major

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

Previous hypersensitivity to tramadol, acetaminophen, any other component of this product, or opioids [see Warnings and Precautions (5.19) ].

Contraindicationsby drug classView label on DailyMed

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

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 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 concurrent use of Hydrocodone Polistirex and Chlorpheniramine Polistirex with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur [ see Warnings and Precautions (5.8) ].

Warnings and precautionsby 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.