Fentanyl and Methylene blue interaction

Fentanyl 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 Fentanyl (FENTANYL CITRATE) label · effective 2026-04-07

Major

• Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.

Warnings and precautionsby drug classView label on DailyMed
Major

…rotation (safely ‎switching the patient to a different opioid moiety) [see Dosage and ‎Administration (2) , Warnings and Precautions (5.7) ] .‎ 5.8 Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of fentanyl with serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed
Major

Monoamine Oxidase Inhibitors Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome [see Warnings and Precautions (5.8) ] or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.2) ].

Drug interactionsby drug classView label on DailyMed
Major

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

Drug interactionsby drug classView label on DailyMed
Moderate

…(less than 50 bpm), 2) any clinically significant cardiac disease, including baseline prolonged QT interval, 3) treatment with Class 1 and Class III antiarrhythmics, 4) treatment with monoamine oxidase inhibitors (MAOI's), 5) concomitant treatment with other drug products known to prolong the QT interval and 6) electrolyte imbalance, in particular hypokalemia and…

Warnings and precautionsby drug classView label on DailyMed

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.