Methylene blue and Milnacipran interaction
Methylene blue and Milnacipran: 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 Milnacipran (Milnacipran Hydrochloride) label · effective 2026-03-19
In addition, do not start milnacipran hydrochloride in a patient who is being treated with linezolid or intravenous methylene blue ( 4.1 , 5.2 ).
Starting milnacipran hydrochloride in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.6 ), Warnings and Precautions ( 5.2 )] .
• Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with milnacipran hydrochloride or within 5 days of stopping treatment with milnacipran hydrochloride.
Do not use milnacipran hydrochloride within 14 days of stopping an MAOI intended to treat psychiatric disorders.
Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with milnacipran hydrochloride or within 5 days of stopping treatment with milnacipran hydrochloride is contraindicated because of an increased risk of serotonin syndrome.
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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.