Levomilnacipran and Tramadol interaction

Levomilnacipran 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 Levomilnacipran (Fetzima) label · effective 2024-04-30

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 FETZIMA 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

Examples: selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Other Serotonergic Drugs Clinical Impact: Concomitant use of FETZIMA with other serotonergic drugs increases the risk of serotonin syndrome.

Drug interactionsby drug classView label on DailyMed
Major

Intervention: Monitor for symptoms of serotonin syndrome when FETZIMA is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems.

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 (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

Use with caution in those taking tranquilizers, antidepressants or abusing alcohol.

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

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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.