Hydrocodone and acetaminophen and Promethazine interaction
Hydrocodone and acetaminophen and Promethazine: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
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
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.
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 ] .
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,…
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 ].
Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see PRECAUTIONS, Drug Interactions ].
From the Promethazine (PROMETHAZINE HYDROCHLORIDE) label · effective 2026-04-16
The impairment may be amplified by concomitant use of other central-nervous-system depressants such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore such agents should either be eliminated or given in reduced dosage in the presence of promethazine…
It should be used with caution in persons with seizure disorders or in persons who are using concomitant medications, such as narcotics or local anesthetics, which may also affect seizure threshold.
Drug Interactions CNS Depressants Promethazine Syrup may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered…
When given concomitantly with Promethazine Syrup, the dose of barbiturates should be reduced by at least one-half, and the dose of narcotics should be reduced by one-quarter to one-half.
CNS Depressants Promethazine Syrup may increase, prolong, or intensify the sedative action of other central-nervous-system depressants, such as alcohol, sedatives/hypnotics (including barbiturates), narcotics, narcotic analgesics, general anesthetics, tricyclic antidepressants, and tranquilizers; therefore, such agents should be avoided or administered in reduced…
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Open in the checkerNot 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.