Methylene blue and Tramadol and acetaminophen interaction
Methylene blue and Tramadol and acetaminophen: 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 and acetaminophen (Tramadol Hydrochloride and Acetaminophen) label · effective 2026-01-01
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use within the last 14 days [see Drug Interactions (7) ].
Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days ( 4 )
Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions (5.10) ] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.3) ] .
Intervention: Do not use tramadol hydrochloride and acetaminophen in patients taking MAOIs or within 14 days of stopping such treatment.
…(SSRIs) and Serotonin-norepinephrine re-uptake inhibitors (SNRIs) antidepressants or anorectics, Tricyclic antidepressants (TCAs), and other tricyclic compounds (e.g., cyclobenzaprine, promethazine, etc.), Other opioids, MAO inhibitors [see Warnings and Precautions (5.10) , Drug Interactions (7) ] Neuroleptics, or Other drugs that reduce the seizure threshold.
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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.