Naltrexone and bupropion and Promethazine and codeine interaction

Naltrexone and bupropion 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 Naltrexone and bupropion (Contrave Extended-Release) label · effective 2025-11-10

Major

…limited to, WELLBUTRIN, WELLBUTRIN SR, WELLBUTRIN XL, APLENZIN and ZYBAN) Bulimia or anorexia nervosa, which increase the risk for seizure [see Warnings and Precautions (5.3) ] Chronic opioid or opiate agonist (e.g., methadone) or partial agonists (e.g., buprenorphine) use, or acute opiate withdrawal [see Warnings and Precautions (5.4) and Drug Interactions (7.2)…

Contraindicationsby drug classView label on DailyMed
Major

Chronic opioid use ( 4 )

Contraindicationsby drug classView label on DailyMed
Major

…Administration (2.1) and Clinical Pharmacology (12.3) ] if a dose is missed, a patient should wait until the next scheduled dose to resume the regular dosing schedule 5.4 Patients Receiving Opioid Analgesics Vulnerability to Opioid Overdose: CONTRAVE should not be administered to patients receiving chronic opioids, due to the naltrexone component, which is an opioid receptor…

Warnings and precautionsby drug classView label on DailyMed
Major

An attempt by a patient to overcome any naltrexone opioid blockade by administering large amounts of exogenous opioids is especially dangerous and may lead to a fatal overdose or life-threatening opioid intoxication (e.g., respiratory arrest, circulatory collapse).

Warnings and precautionsby drug classView label on DailyMed
Moderate

In patients requiring intermittent opiate treatment, CONTRAVE therapy should be temporarily discontinued and lower doses of opioids may be needed.

Warnings and precautionsby drug classView label on DailyMed

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

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

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.