Acetaminophen And Codeine and Melitracen: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Melitracen
No brand names on record
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.
You've been prescribed acetaminophen with codeine (a pain reliever) along with melitracen (a medicine that affects mood). Both can raise serotonin, a brain chemical. When two medicines do this together, there's a small chance of a reaction called serotonin syndrome. Signs can include feeling agitated or restless, a fast heartbeat, sweating, shaking, muscle twitching, or a high fever.
This is mostly a theoretical concern, and many people take combinations like this safely. The good news is your care team can manage it by watching you closely, especially when you first start or when doses change. Keep taking both as prescribed, and let your doctor or pharmacist know if you feel any of these symptoms.
Effect: Additive serotonergic activity increasing the theoretical risk of serotonin syndrome when codeine is combined with melitracen (a tricyclic antidepressant with serotonergic properties).
- Mechanism: Additive serotonergic effects (PD interaction), not a metabolic/enzyme interaction.
- Direction: Increased serotonergic burden.
- Evidence: Theoretical; onset unspecified.
- Severity: Major.
- Management: If used together, monitor for clonus, hyperreflexia, autonomic instability, hyperthermia, agitation, and mental status changes, especially at initiation and dose changes. Discontinue codeine and manage supportively if serotonin syndrome is suspected.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like codeine are taken together with serotonergic agents. When such combined therapy is necessary, monitor the patient closely, especially when starting treatment and when doses are being changed. Should serotonin syndrome be suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
What your care team may do:
- Keep a closer eye on you, especially when either medicine is started or a dose is changed.
- Individualize and adjust dosing as needed for your situation.
- Stop the codeine and treat symptoms if signs of serotonin syndrome appear.
What you can do: Keep taking both exactly as prescribed. Watch for agitation, confusion, fast heartbeat, sweating, shaking, muscle stiffness or twitching, or fever, and contact your doctor or pharmacist right away if these occur. Don't start or stop either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Melitracen together?
Taking codeine with melitracen slightly raises the theoretical risk of serotonin syndrome, so watch for symptoms like agitation, rapid heartbeat, sweating, or muscle twitching and report them promptly. Your care team can manage this with monitoring and dose adjustments. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Melitracen interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Acetaminophen And Codeine and Melitracen interaction managed?
What your care team may do: Keep a closer eye on you, especially when either medicine is started or a dose is changed. Individualize and adjust dosing as needed for your situation. Stop the codeine and treat symptoms if signs of serotonin syndrome appear. What you can do: Keep taking both exactly as prescribed. Watch for agitation, confusion, fast heartbeat, sweating, shaking, muscle stiffness or… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Melitracen 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 (3)
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp (per DailyMed), Eatontown, NJ, 2016. DailyMed
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
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