Methylene blue and Tramadol interaction
Methylene blue and Tramadol: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Methylene blue (PROVAYBLUE) label · effective 2025-05-28
WARNING: SEROTONIN 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.
Avoid concomitant use of PROVAYBLUE with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and opioids. [see Warnings and Precautions ( 5.1 ) and Drug Interactions ( 7.1 )].
WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS See full prescribing information for complete boxed warning.
PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids.
Serotonin Syndrome with Concomitant Use of Serotonergic Drugs and Opioids The development of serotonin syndrome has been reported with the use of methylene blue class products.
From the Tramadol (Tramadol Hydrochloride Extended-Release) label · effective 2026-01-23
…gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.16) ] Hypersensitivity to tramadol (e.g., anaphylaxis) [see Warnings and Precautions (5.17) , Adverse Reactions (6) ] Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7) ] Children younger than 12 years of age.
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days.
Intervention: Do not use Tramadol Hydrochloride Extended-Release Capsules in patients taking MAOIs or within 14 days of stopping such treatment.
Risk is increased with higher than recommended doses and concomitant use of SSRIs, SNRIs, anorectics, tricyclic antidepressants and other tricyclic compounds, other opioids, MAOIs, neuroleptics, other drugs that reduce seizure threshold, in patients with epilepsy or at risk for seizures.
…serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressants or anorectics, Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), Other opioids, Monoamine oxidase inhibitors (MAOIs) [see Warnings and Precautions (5.9) , Drug Interactions (7) ] , Neuroleptics, or Other drugs that reduce the seizure threshold.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.