What the FDA labels say about taking them together
Desvenlafaxine and methadone
Desvenlafaxine's FDA label (Pristiq Extended-Release) of April 28, 2026 names methadone in its warnings and precautions section; methadone's label does not name desvenlafaxine itself but warns about its class (SNRIs (serotonin and norepinephrine reuptake inhibitors)). The desvenlafaxine 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 desvenlafaxine FDA label on DailyMed (effective January 27, 2023, Alembic Pharmaceuticals Limited); the methadone FDA label on DailyMed (effective December 8, 2025, Epic Pharma, LLC).
What does the desvenlafaxine label say about methadone?
Pristiq Extended-Release label (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., April 28, 2026), warnings and precautionsThe 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 (Pristiq Extended-Release, NDA021992), Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., effective April 28, 2026 (SPL set 0f43610c-f290-46ea-d186-4f998ed99fce), via openFDA
Source: FDA drug label (Desvenlafaxine), Alembic Pharmaceuticals Limited, effective January 27, 2023 (SPL set 9f74708c-6f6a-46cf-8c79-87a25c2bb6f8), via openFDA; the full label on DailyMed
What does the methadone label say about desvenlafaxine?
Methadone's label does not name desvenlafaxine itself; it warns about its class (SNRIs (serotonin and norepinephrine reuptake inhibitors)):
Methadone label, warnings and precautionsSyndrome 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 precautionsSyndrome 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
| Desvenlafaxine | Methadone | |
|---|---|---|
| Labeled for | Depression | Pain, Opioid use disorder |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.396 per unit 50 mg | $0.177 per tablet 10 mg tablet |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once