Morphine Injection and Methylene Blue: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methylene Blue
Morphine Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of the profound sedation, respiratory depression, hypotension, coma and an increased risk of serotonin syndrome
Interaction Deep Dive
The concurrent administration of morphine with methylene blue (MAOI) is contraindicated because it may potentiate the effects of morphine, including respiratory depression, coma, confusion and serotonin syndrome. Do not use morphine in patients taking MAOIs or within 14 days of methylene blue. If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue morphine if serotonin syndrome is suspected143. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of other opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression 562.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
Literature reports
2 reports — tap to read
a) Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs 56.
b) In a case report, a 57-year-old woman that was well controlled on phenelzine for moderate depression presented to the hospital with signs and symptoms of serotonin syndrome. Ten days earlier, she was treated for cellulitis and received antiinfective agents, acetaminophen, and morphine sulfate oral solution. The patient was discharged after 7 days and then presented to the emergency department 3 days later with complaints of increasing visual hallucinations, restlessness, photophobia, dizziness, neck stiffness, occipital headache, sweating, and nausea for the last week. Morphine sulfate and phenelzine were stopped on admission and general supportive measures, including oxygen and fluids, were started. The patient was discharged 2 days later after full resolution of symptoms, and phenelzine was restarted on discharge without complications. The Drug Interaction Probability Scale (DIPS) indicated a probable relationship between phenelzine and morphine with a score of 6 7.
Common questions
Can I take Morphine Injection and Methylene Blue together?
Increased risk of the profound sedation, respiratory depression, hypotension, coma and an increased risk of serotonin syndrome Always confirm with your pharmacist or prescriber before making any change.
How serious is the Morphine Injection and Methylene Blue interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Morphine Injection or Methylene Blue need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: MS CONTIN(R) oral extended-release tablets, morphine sulfate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: INFUMORPH intrathecal, epidural injection, morphine sulfate intrathecal, epidural injection. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Morphine sulfate oral tablets, morphine sulfate oral tablets. Hikma Pharmaceuticals USA Inc.(Per FDA), Berkeley, NJ, 2023. DailyMed
- Product Information: Morphine sulfate oral solution, morphine sulfate oral solution. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: DURAMORPH intravenous, epidural, intrathecal injection, morphine sulfate intravenous, epidural, intrathecal injection. Hikma Pharmaceuticals USA Inc (Per FDA), Berkeley, NJ, 2023. DailyMed
- Product Information: Morphine sulfate intravenous injection, morphine sulfate intravenous injection. Mallinckrodt Inc (Per FDA), St. Louis, MO, 2023. DailyMed
- Mateo-Carrasco H, Munoz-Aguilera EM, Garcia-Torrecillas JM, et al: Serotonin syndrome probably triggered by a morphine-phenelzine interaction. Pharmacotherapy 2015; 35(6):e102-e105. PubMed
Keep reading about Methylene Blue
Keep reading about Morphine Injection
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