Buprenorphine and Methylene blue interaction

Buprenorphine and Methylene blue: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Buprenorphine (BELBUCA) label · effective 2026-01-02

Major

Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2) ].

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Major

Intervention: The use of BELBUCA is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

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Major

Serotonergic Drugs : Concomitant use may result in serotonin syndrome.

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Major

Avoid concomitant use in patients receiving MAOIs or within 14 days of stopping treatment with an MAOI.

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Moderate

Monoamine Oxidase Inhibitors (MAOIs) : Can potentiate the effects of buprenorphine.

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From the Methylene blue (PROVAYBLUE) label · effective 2025-05-28

Major

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.

Boxed warningby drug classView label on DailyMed
Major

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 )].

Boxed warningby drug classView label on DailyMed
Major

WARNING: SEROTONIN SYNDROME WITH CONCOMITANT USE OF SEROTONERGIC DRUGS AND OPIOIDS See full prescribing information for complete boxed warning.

Boxed warningby drug classView label on DailyMed
Major

PROVAYBLUE may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs and opioids.

Boxed warningby drug classView label on DailyMed
Major

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.

Warnings and precautionsby drug classView label on DailyMed

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Not 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.