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What the FDA labels say about taking them together

Methadone and paroxetine

Paroxetine's FDA label of February 12, 2026 names methadone in its warnings and precautions section; methadone's label does not name paroxetine itself but warns about its class (serotonin reuptake inhibitors). The paroxetine 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 methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC); the paroxetine FDA label on DailyMed (effective February 12, 2026, Mylan Pharmaceuticals Inc.).

What does the methadone label say about paroxetine?

Methadone's label does not name paroxetine itself; it warns about its class (serotonin 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

What does the paroxetine label say about methadone?

Paroxetine 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 (Brisdelle, NDA204516), Legacy Pharma USA, Inc., effective April 28, 2025 (SPL set 502311b3-b617-4cbd-a3ab-a60f2c62880a), via openFDA

Source: FDA drug label (Paroxetine), Mylan Pharmaceuticals Inc., effective February 12, 2026 (SPL set 89dd7e24-85fc-4152-89ea-47ec2b48a1ed), 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

18Methadone generic labelers
45Paroxetine generic labelers
MethadoneParoxetine
Labeled forPain, Opioid use disorderDepression, Anxiety, Menopause symptoms
Boxed warningYesYes
Pharmacy cost (NADAC)$0.177 per tablet 10 mg tablet$0.0611 per tablet 20 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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