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What the FDA labels say about taking them together

Levomilnacipran and methadone

Levomilnacipran's FDA label of April 30, 2024 names methadone in its warnings and precautions section; methadone's label does not name levomilnacipran itself but warns about its class (SNRIs (serotonin and norepinephrine reuptake inhibitors)). The levomilnacipran label: “The risk is increased with concomitant use of other serotonergic drugs and with drugs that impair metabolism of serotonin, i.e., MAOIs.”

Check it at the source: the levomilnacipran FDA label on DailyMed (effective April 30, 2024, Allergan, Inc.); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).

What does the levomilnacipran label say about methadone?

Levomilnacipran label, warnings and precautions

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. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Contraindications ( 4 ), Drug Interactions ( 7.1 )].

Source: FDA drug label (Fetzima), NDA204168 (Abbvie), as published by Allergan, Inc., effective April 30, 2024 (SPL set f371258d-91b3-4b6a-ac99-434a1964c3af), via openFDA; the full label on DailyMed

What does the methadone label say about levomilnacipran?

Methadone's label does not name levomilnacipran itself; it warns about its class (SNRIs (serotonin and norepinephrine reuptake inhibitors)):

Methadone label, warnings and precautions

Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of methadone hydrochloride tablets with serotonergic drugs. 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 …

Methadone label, warnings and precautions

Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of DISKETS with serotonergic drugs. 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 …

Source: FDA drug label (Methadone Hydrochloride), Epic Pharma, LLC, effective December 8, 2025 (SPL set 6da7501b-b881-4bc7-891a-74214a00a3ac), via openFDA; the full label on DailyMed

These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.

Both medicines on the record

0Levomilnacipran generic labelers
18Methadone generic labelers
LevomilnacipranMethadone
Labeled forDepressionPain, Opioid use disorder
Boxed warningYesYes
Pharmacy cost (NADAC)$17.61 per unit 20-40 mg titration pak$0.177 per tablet 10 mg tablet
Shortage nowNo current entryNo current entry

Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)

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