Milnacipran and Tramadol interaction

Milnacipran and Tramadol: 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.

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

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 (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23

Moderate

Serotonin Syndrome Risk: Potentially life-threatening condition could result from use of Tramadol Hydrochloride Extended-Release Capsules, particularly during concomitant use of serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risk is increased with higher than recommended doses and concomitant use of SSRIs, SNRIs, anorectics, tricyclic antidepressants and other tricyclic compounds, other opioids, MAOIs, neuroleptics, other drugs that reduce seizure threshold, in patients with epilepsy or at risk for seizures.

Warnings and precautionsby drug classView label on DailyMed
Moderate

…3A4 inhibitors, or 2D6 inhibitors with Tramadol Hydrochloride Extended-Release Capsules requires careful consideration of the effects on the parent drug, tramadol which is a weak serotonin and norepinephrine reuptake inhibitor and mu-opioid agonist, and the active metabolite, M1, which is more potent than tramadol in mu-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 products, including Tramadol Hydrochloride Extended-Release Capsules, particularly during concomitant use with serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Concomitant use of tramadol increases the seizure risk in patients taking: [see Drug Interactions (7) ] Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants or anorectics, Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), Other opioids,…

Warnings and precautionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

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.