Hydrocodone and Promethazine and codeine interaction

Hydrocodone and Promethazine and codeine: 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 Promethazine and codeine (Promethazine Hydrochloride and Codeine Phosphate) label · effective 2025-12-18

Major

…PROMETHAZINE AND RESPIRATORY DEPRESSION IN CHILDREN; MEDICATION ERRORS; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; NEONATAL OPIOID WITHDRAWAL SYNDROME Addiction, Abuse, and Misuse Promethazine HCl and Codeine Phosphate Oral Solution exposes patients and other users to the risks…

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 Promethazine HCl and Codeine Phosphate Oral Solution in patients taking benzodiazepines, other CNS depressants, or alcohol [ see Warnings and Precautions (5.10) , Drug Interactions (7.4) ].

Boxed warningby drug classView label on DailyMed
Major

( 5.9 , 7.1 , 7.2 , 7.3 ) 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

Persons known to be hypersensitive to certain other opioids may exhibit cross-reactivity to codeine.

Contraindicationsby drug classView label on DailyMed

From the Hydrocodone (Hysingla ER) label · effective 2026-05-29

Major

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYSINGLA ER Addiction, Abuse, and Misuse Because the use of HYSINGLA ER 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 these…

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 HYSINGLA ER and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , 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

Overestimating the HYSINGLA ER dosage when converting patients from another opioid product can result in fatal overdose with the first dose.

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.