What the FDA labels say about taking them together
Methadone and venlafaxine
Venlafaxine's FDA label of August 15, 2023 names methadone in its warnings and precautions section; methadone's label does not name venlafaxine itself but warns about its class (SNRIs (serotonin and norepinephrine reuptake inhibitors)). The venlafaxine 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 venlafaxine FDA label on DailyMed (effective August 15, 2023, Viatris Specialty LLC).
What does the methadone label say about venlafaxine?
Methadone's label does not name venlafaxine 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
What does the venlafaxine label say about methadone?
Venlafaxine label, 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 (Venlafaxine Hydrochloride, NDA022104), Trigen Laboratories, LLC, effective July 31, 2025 (SPL set fdaed1c2-dd0a-4bf3-975a-86fe3e7f0c97), via openFDA
Source: FDA drug label (Effexor XR), NDA020699 (Upjohn), as published by Viatris Specialty LLC, effective August 15, 2023 (SPL set c848a5d8-ba94-4c84-80e3-0bf35fb8e32e), 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
| Methadone | Venlafaxine | |
|---|---|---|
| Labeled for | Pain, Opioid use disorder | Depression, Anxiety |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $0.177 per tablet 10 mg tablet | $0.0799 per capsule 75 mg capsule |
| 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