What the FDA labels say about taking them together
Methylene blue and tramadol
Tramadol's FDA label of March 5, 2026 names methylene blue in its drug interactions section; methylene blue's label does not name tramadol itself but warns about its class (Opioids (opioid agonists)). The tramadol 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 methylene blue FDA label on DailyMed (effective May 28, 2025, American Regent, Inc.); the tramadol FDA label on DailyMed (effective March 5, 2026, Lupin Pharmaceuticals, Inc.).
What does the methylene blue label say about tramadol?
Methylene blue's label does not name tramadol itself; it warns about its class (Opioids (opioid agonists)):
Methylene blue label, boxed warningSEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids.
Methylene blue label, boxed warningSEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS See full prescribing information for complete boxed warning.
Source: FDA drug label (PROVAYBLUE), NDA204630 (Provepharm Sas), as published by American Regent, Inc., effective May 28, 2025 (SPL set 4f6848e5-35ed-4046-b13c-3032b5ba3232), via openFDA; the full label on DailyMed
What does the tramadol label say about methylene blue?
Tramadol 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. … inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Tramadol 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 (Tramadol Hydrochloride Extended-Release, NDA022370), Trigen Laboratories, LLC, effective January 23, 2026 (SPL set c0bc7218-3fd0-4646-96f4-25355fc84aa9), via openFDA
Source: FDA drug label (Tramadol Hydrochloride, NDA214044), TruPharma, LLC, effective January 25, 2023 (SPL set aea56ff9-94ac-47a8-8f15-8790d538973b), via openFDA
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
| Methylene blue | Tramadol | |
|---|---|---|
| Labeled for | n/a | 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