What the FDA labels say about taking them together
Tapentadol and trazodone
Tapentadol's FDA label of February 26, 2026 names trazodone in its drug interactions section; the trazodone labels PlainMeds reads (2) do not name tapentadol. The tapentadol label: “The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.”
Check it at the source: the tapentadol FDA label on DailyMed (effective February 26, 2026, Hikma Pharmaceuticals USA Inc.); the trazodone FDA label on DailyMed (effective January 22, 2026, Zydus Pharmaceuticals USA Inc.).
What does the tapentadol label say about trazodone?
Tapentadol label, drug interactionsSerotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. … 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and …
Tapentadol label, warnings and precautionsSerotonergic 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 muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including monoamine oxidase inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) [see Drug Interactions (7) ].
Source: FDA drug label (TAPENTADOL), Hikma Pharmaceuticals USA Inc., effective February 26, 2026 (SPL set 863f3fd3-1e8d-41b0-855f-8f9a29237cda), via openFDA; the full label on DailyMed
What does the trazodone label say about tapentadol?
Trazodone's label (effective January 22, 2026) and its 1 other brand-application label do not name tapentadol in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Trazodone Hydrochloride), Zydus Pharmaceuticals USA Inc., effective January 22, 2026 (SPL set 704aebf9-2fff-4ef3-8323-9ff0d7f0ffd9), 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
| Tapentadol | Trazodone | |
|---|---|---|
| Labeled for | Pain | Depression |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $14.48 per tablet 100 mg tablet | $0.0307 per tablet 50 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