Duloxetine and Tramadol and acetaminophen interaction

Duloxetine and Tramadol and acetaminophen: 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 Duloxetine label · effective 2026-03-02

Major

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents but also when taken alone.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of Duloxetine Delayed-Release Capsules with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Warnings and precautionsby drug classView label on DailyMed
Major

Other Serotonergic Drugs Prevention or Management Monitor for symptoms of serotonin syndrome when Duloxetine Delayed-Release Capsules is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems.

Drug interactionsby drug classView label on DailyMed
Major

Mechanism and Clinical Effect(s) Concomitant use of Duloxetine Delayed-Release Capsules with other serotonergic drugs increases the risk of serotonin syndrome.

Drug interactionsby drug classView label on DailyMed
Moderate

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

Warnings and precautionsby drug classView label on DailyMed

From the Tramadol and acetaminophen (Tramadol Hydrochloride and Acetaminophen) label · effective 2026-01-01

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 tramadol are complex.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 [see Warnings and Precautions (5.7) , Drug Interactions (7) ] .

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 tramadol are complex.

Boxed warningby drug classView label on DailyMed
Moderate

Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors on levels of tramadol and M1 from tramadol hydrochloride and acetaminophen are complex.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risks of Concomitant Use or Discontinuation of Cytochrome P450 2D6 Inhibitors The concomitant use of tramadol hydrochloride and acetaminophen with all cytochrome P450 2D6 inhibitors (e.g., amiodarone, quinidine) may result in an increase in tramadol plasma levels and a decrease in the levels of the active metabolite, M1.

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.