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What the FDA labels say about taking them together

Hydrocodone and tramadol

Hydrocodone's FDA label of May 29, 2026 names tramadol in its drug interactions section; tramadol's label does not name hydrocodone itself but warns about its class (Opioids (opioid agonists)). The hydrocodone 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 hydrocodone FDA label on DailyMed (effective May 29, 2026); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).

What does the hydrocodone label say about tramadol?

Hydrocodone label, drug interactions

Serotonergic 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 inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous …

Source: FDA drug label (Hysingla ER), Knoa Pharma LLC, effective May 29, 2026 (SPL set b7d23ac2-e776-9f62-3290-c64c2d6eb353), via openFDA; the full label on DailyMed

What does the tramadol label say about hydrocodone?

Tramadol's label does not name hydrocodone itself; it warns about its class (Opioids (opioid agonists)):

Tramadol label, boxed warning

Instruct patients to swallow tramadol hydrochloride extended-release tablets whole to avoid exposure to a potentially fatal dose of tramadol. ( 5.2 ) Accidental ingestion of tramadol hydrochloride extended-release tablets, especially by children, can result in a fatal overdose of tramadol. ( 5.2 ) Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.

Tramadol label, boxed warning

Instruct patients to swallow Tramadol Hydrochloride Extended-Release Capsules intact, and not to split, chew, crush, or dissolve content of the capsules to avoid exposure to a potentially fatal dose of tramadol. ( 2.1 , 5.2 ) Accidental ingestion of Tramadol Hydrochloride Extended-Release Capsules, especially by children, can result in a fatal overdose of tramadol. …

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

1Hydrocodone generic labelers
39Tramadol generic labelers
HydrocodoneTramadol
Labeled forPainPain
Boxed warningYesYes
Pharmacy cost (NADAC)$7.95 per capsule 15 mg capsule$0.0248 per tablet 50 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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