Butalbital, aspirin, caffeine, and codeine and Fluoxetine interaction

Butalbital, aspirin, caffeine, and codeine and Fluoxetine: 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 Butalbital, aspirin, caffeine, and codeine (BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE) label · effective 2026-01-15

Major

Examples paroxetine, fluoxetine, bupropion, quinidine Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death.

Drug interactionsnames FluoxetineView 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.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with BUTALBITAL, ASPIRIN, CAFFEINE and CODEINE PHOSPHATE requires careful consideration of the effects on codeine, and the active metabolite, morphine.

Boxed warningby drug classView label on DailyMed
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.

Boxed warningby drug classView label on DailyMed
Major

Intervention: Avoid concomitant use Serotonergic Drugs : Concomitant use may result in serotonin syndrome.

Drug interactionsby drug classView label on DailyMed

From the Fluoxetine (Prozac) label · effective 2026-01-08

Moderate

Use with NSAIDs, aspirin, warfarin, or other drugs that affect coagulation may potentiate the risk of gastrointestinal or other bleeding ( 5.7 )

Warnings and precautionsnames Butalbital, aspirin, caffeine, and codeineView label on DailyMed
Moderate

Patients should be cautioned about the increased risk of bleeding associated with the concomitant use of fluoxetine and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation [see Drug Interactions ( 7.4 )] .

Warnings and precautionsnames Butalbital, aspirin, caffeine, and codeineView label on DailyMed
Moderate

Serotonergic Drugs: ( 2.9 , 2.10 , 4.1 , 5.2 ) Drugs that Interfere with Hemostasis (e.g. NSAIDs, Aspirin, Warfarin): May potentiate the risk of bleeding ( 7.4 )

Drug interactionsnames Butalbital, aspirin, caffeine, and codeineView label on DailyMed
Moderate

Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding.

Drug interactionsnames Butalbital, aspirin, caffeine, and codeineView label on DailyMed
Moderate

The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, meperidine, methadone, buspirone, amphetamines, and St.

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.