Dextromethorphan and quinidine and Promethazine and codeine interaction

Dextromethorphan and quinidine 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

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.

Boxed warningby drug classView label on DailyMed
Major

Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking a CYP3A4 inhibitor, CYP3A4 inducer, or 2D6 inhibitor [ see Warnings and Precautions (5.9) , Drug Interactions (7.1 , 7.2 , 7.3 ) ].

Boxed warningby drug classView label on DailyMed
Major

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex, requiring careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine.

Boxed warningby drug classView label on DailyMed
Major

Avoid the use of Promethazine HCl and Codeine Phosphate Oral Solution in patients who are taking a CYP2D6 inhibitor.

Warnings and precautionsby drug classView label on DailyMed
Major

Serotonergic Drugs : Concomitant use may result in serotonin syndrome.

Drug interactionsby drug classView label on DailyMed

From the Dextromethorphan and quinidine (Nuedexta) label · effective 2026-01-22

Moderate

Anticholinergic effects of quinidine: Monitor for worsening in myasthenia gravis and other sensitive conditions.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Anticholinergic Effects of Q uinidine Monitor for worsening clinical condition in myasthenia gravis and other conditions that may be adversely affected by anticholinergic effects.

Warnings and precautionsby drug classView label on DailyMed
Minor

In cases of prodrugs whose actions are mediated by the CYP2D6-produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in the presence of NUEDEXTA due to quinidine-mediated inhibition of…

Drug interactionsnames Promethazine and codeineView 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.