Milnacipran and Tramadol and acetaminophen interaction

Milnacipran 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 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.

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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

Serotonergic Drugs Serotonin syndrome can occur with use of milnacipran hydrochloride and other serotonergic drugs (other SNRIs, SSRIs, triptans, tricyclic antidepressants, opioids, lithium, tryptophan, buspirone, amphetamines, and St.

Drug interactionsby drug classView label on DailyMed

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

Moderate

…inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, which is a weak serotonin and norepinephrine reuptake inhibitor and μ-opioid agonist, and the active metabolite, M1, which is more potent than tramadol in μ-opioid receptor binding [see Drug Interactions…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Serotonin Syndrome Risk Cases of serotonin syndrome, a potentially life-threatening condition, have been reported with the use of tramadol, including tramadol hydrochloride and acetaminophen, during concomitant use with serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Selective serotonin re-uptake inhibitors (SSRIs) and Serotonin-norepinephrine re-uptake inhibitors (SNRIs) antidepressants or anorectics, Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), Other opioids, MAO inhibitors [see Warnings and Precautions (5.10) , Drug Interactions (7) ] Neuroleptics, or Other…

Warnings and precautionsby drug classView label on DailyMed
Minor

Can occur with use of tramadol alone, with concomitant use of serotonergic drugs, with drugs that impair metabolism of serotonin or tramadol.

Warnings and precautionsby drug classView label on DailyMed
Minor

Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone),…

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.