Duloxetine and Milnacipran interaction

Duloxetine and Milnacipran: 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 Milnacipran (Milnacipran Hydrochloride) label · effective 2026-03-19

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 milnacipran hydrochloride 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
Moderate

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

Warnings and precautionsby drug classView label on DailyMed
Minor

If it occurs, discontinue milnacipran hydrochloride and any other serotonergic agents, and initiate supportive treatment ( 5.2 ).

Warnings and precautionsby drug classView label on DailyMed
Minor

The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients.

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.