Acetaminophen And Codeine and Mirtazapine: 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
Mirtazapine
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's going on: Your pain medicine contains codeine, and both codeine and mirtazapine (Remeron) can raise levels of a brain chemical called serotonin. When two medicines do this together, there's a small chance of a reaction called serotonin syndrome.
Watch for symptoms like agitation, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, or feeling confused. These are uncommon, and this warning is based more on caution than on frequent real-world reports. Many people take both safely. Keep taking both as prescribed, and let your pharmacist or doctor know if any of those symptoms show up, especially in the first weeks or after a dose change.
Effect: Additive serotonergic activity, theoretically increasing risk of serotonin syndrome. Codeine has weak serotonergic properties and mirtazapine is a noradrenergic/serotonergic antidepressant; the concern is pharmacodynamic (additive), not pharmacokinetic.
- Direction/magnitude: Increased serotonergic tone; magnitude not quantified.
- Onset: Unspecified; risk highest at initiation and dose escalation.
- Evidence: Theoretical.
- Monitoring: Watch for autonomic instability, neuromuscular abnormalities (clonus, hyperreflexia, rigidity), and mental status changes.
- Management: Co-use acceptable with vigilance; discontinue codeine 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 use cannot be avoided, monitor the patient closely, especially when starting therapy and when doses are being changed. If serotonin syndrome is suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
You can usually take both, with some watchfulness from your care team.
- Keep taking both medicines as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may watch you more closely when starting either drug or changing a dose, since that is when risk is highest.
- Learn the warning signs: agitation, fast heart rate, sweating, shivering, muscle twitching or stiffness, or confusion.
- Seek care promptly and contact your prescriber if these symptoms appear. The codeine may be stopped if serotonin syndrome is suspected.
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 Mirtazapine together?
Taking codeine and mirtazapine together carries a small, mostly theoretical risk of serotonin syndrome. Keep taking both as prescribed, watch for symptoms like agitation, sweating, shivering, or muscle twitching, and call your care team if they appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Mirtazapine 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 Mirtazapine interaction managed?
You can usually take both, with some watchfulness from your care team. Keep taking both medicines as prescribed unless your doctor or pharmacist tells you otherwise. Your team may watch you more closely when starting either drug or changing a dose, since that is when risk is highest. Learn the warning signs: agitation, fast heart rate, sweating, shivering, muscle twitching or stiffness, or confusi… 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 Mirtazapine 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
Keep reading about Acetaminophen And Codeine
Keep reading about Mirtazapine
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