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What the FDA labels say about taking them together

Remifentanil and tramadol

Remifentanil's FDA label of December 15, 2025 names tramadol in its drug interactions section; tramadol's label does not name remifentanil itself but warns about its class (Opioids (opioid agonists)). The remifentanil 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 remifentanil FDA label on DailyMed (effective December 15, 2025, Mylan Institutional LLC); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).

What does the remifentanil label say about tramadol?

Remifentanil 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 effect 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 …

Remifentanil label, warnings and precautions

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 muscle relaxants (i.e., cyclobenzaprine, metaxalone), and drugs that impair metabolism of serotonin (including MAO 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 (Ultiva), Mylan Institutional LLC, effective December 15, 2025 (SPL set 4dbcb8f9-1987-4b66-bd2f-d251fda0be10), via openFDA; the full label on DailyMed

What does the tramadol label say about remifentanil?

Tramadol's label does not name remifentanil 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

2Remifentanil generic labelers
39Tramadol generic labelers
RemifentanilTramadol
Labeled forn/aPain
Boxed warningYesYes
Pharmacy cost (NADAC)n/a$0.0248 per tablet 50 mg tablet
Shortage nowIn shortageNo 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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