What the FDA labels say about taking them together
Acetaminophen/benzhydrocodone and tramadol
Acetaminophen/benzhydrocodone's FDA label of January 7, 2025 names tramadol in its drug interactions section; the tramadol labels PlainMeds reads (3) do not name acetaminophen/benzhydrocodone. The acetaminophen/benzhydrocodone 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 acetaminophen/benzhydrocodone FDA label on DailyMed (effective January 7, 2025, Zevra Therapeutics, Inc.); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the acetaminophen/benzhydrocodone label say about tramadol?
Acetaminophen/benzhydrocodone 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. … receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e. cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and …
Source: FDA drug label (APADAZ), Zevra Therapeutics, Inc., effective January 7, 2025 (SPL set 0590d4e5-7107-4015-a6a8-deac14265aa2), via openFDA; the full label on DailyMed
What does the tramadol label say about acetaminophen/benzhydrocodone?
Tramadol's label (effective March 5, 2026) and its 2 other brand-application labels do not name acetaminophen/benzhydrocodone in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (TRAMADOL HYDROCHLORIDE), Lupin Pharmaceuticals, Inc., effective March 5, 2026 (SPL set 46bb9ae6-3ee8-463c-badb-c7a45a89b84b), 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
| Acetaminophen/benzhydrocodone | Tramadol | |
|---|---|---|
| Labeled for | Pain | Pain |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | n/a | $0.0248 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