What the FDA labels say about taking them together
Fentanyl and tramadol
Fentanyl's FDA label of March 6, 2026 names tramadol in its drug interactions section; tramadol's label does not name fentanyl itself but warns about its class (Opioids (opioid agonists)). The fentanyl label: “The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome [see.”
Check it at the source: the fentanyl FDA label on DailyMed (effective March 6, 2026, Hikma Pharmaceuticals USA Inc.); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the fentanyl label say about tramadol?
Fentanyl 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 [see. … 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 …
Fentanyl 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, trazadone, 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 (Fentanyl Citrate, NDA019115), Hospira, Inc., effective August 24, 2026 (SPL set bfa8018a-4cbc-434b-e09e-782872b0340a), via openFDA
Source: FDA drug label (Fentanyl Citrate), Hikma Pharmaceuticals USA Inc., effective March 6, 2026 (SPL set ce5db1c2-feb1-4ad2-847a-d02e865bd47e), via openFDA; the full label on DailyMed
What does the tramadol label say about fentanyl?
Tramadol's label does not name fentanyl itself; it warns about its class (Opioids (opioid agonists)):
Tramadol label, boxed warningInstruct 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 warningInstruct 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
| Fentanyl | Tramadol | |
|---|---|---|
| Labeled for | Pain | Pain |
| Boxed warning | Yes | Yes |
| Pharmacy cost (NADAC) | $1.79 per mL 100 mcg/2 mL vial | $0.0248 per tablet 50 mg tablet |
| Shortage now | In shortage | 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