Milnacipran and Paroxetine interaction

Milnacipran and Paroxetine: 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 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

Serotonin Syndrome Selective-serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), including milnacipran hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition.

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
Major

Bleeding events related to SSRIs and SNRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

Warnings and precautionsby drug classView label on DailyMed
Major

Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of SSRIs and SNRIs, including milnacipran hydrochloride, with MAOIs increases the risk of serotonin syndrome.

Drug interactionsby drug classView label on DailyMed

From the Paroxetine (PAROXETINE HYDROCHLORIDE) label · effective 2026-09-16

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

Serotonin Syndrome Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including Paroxetine HCL CR, can precipitate serotonin syndrome, a potentially life-threatening condition.

Warnings and precautionsby drug classView label on DailyMed
Major

If concomitant use of Paroxetine HCL CR 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

If serotonin syndrome occurs, consider discontinuation of Paroxetine HCL CR and/or concomitant serotonergic drugs [see Warnings and Precautions ( 5.2 )].

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

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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.