Amoxapine and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Amoxapine
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) and amoxapine (a medicine for depression). Both can affect the body in similar ways, so using them together can add up.
First, both nudge serotonin levels, and too much serotonin can cause a rare reaction called serotonin syndrome (shaking, fast heartbeat, sweating, confusion, agitation). Second, both can slow down your gut and bladder, which may lead to serious constipation or trouble urinating. This is based on theory more than strong proof, so try not to worry. Your care team can manage it by watching you closely, especially when you first start or change a dose. Call them if you feel any of these symptoms.
Additive risk: combining codeine (opioid) with amoxapine (a tricyclic-type antidepressant with serotonergic and anticholinergic activity) may produce additive effects.
- Serotonin syndrome: additive serotonergic activity; watch for agitation, hyperthermia, clonus, autonomic instability, altered mental status.
- GI/GU: additive reduction in gut motility and anticholinergic load raising risk of urinary retention, severe constipation, and potentially paralytic ileus.
Evidence: theoretical. Onset: unspecified. Severity: major. Management: monitor closely during initiation and dose adjustment; assess bowel/bladder function; discontinue codeine if serotonin syndrome is suspected. Doses may be individualized by the prescriber.
What happens
Increased risk of paralytic ileus; increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of opioids, such as codeine, with serotonergic drugs has resulted in serotonin syndrome. Additionally, the concomitant use of codeine with anticholinergic drugs may increase the risk of urinary retention and severe constipation, which may lead to paralytic ileus. If concomitant use is needed, closely monitor the patient for urinary retention, severe constipation, and signs and symptoms of serotonin syndrome1. during treatment initiation and dose adjustment. Discontinue codeine if serotonin syndrome is suspected 2.
Why it happens (mechanism)
Additive effects on gastric motility; additive serotonergic effects
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with closer monitoring.
- Your team may watch you more closely when you start or change a dose, and doses may be adjusted and individualized.
- Watch for serotonin syndrome: agitation, confusion, fast heartbeat, sweating, tremor, or fever.
- Watch for severe constipation or trouble urinating, which need prompt attention.
Contact your pharmacist or prescriber if any of these appear. Seek urgent care for serotonin syndrome symptoms; your codeine may be stopped if it is suspected.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Amoxapine and Acetaminophen And Codeine together?
Taking acetaminophen/codeine with amoxapine can add up to raise the risk of serotonin syndrome and of severe constipation or urinary retention (possibly paralytic ileus). Keep taking both as prescribed, but have your care team monitor you closely and call them right away if warning symptoms appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amoxapine and Acetaminophen And Codeine 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 Amoxapine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This combination can be managed with closer monitoring. Your team may watch you more closely when you start or change a dose, and doses may be adjusted and individualized. Watch for serotonin syndrome: agitation, confusion, fast heartbeat, sweating, tremor, or fever. Watch for severe constipation or trouble urinati… 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 Amoxapine or Acetaminophen And Codeine 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 (2)
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp (per DailyMed), Eatontown, NJ, 2016. DailyMed
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Amoxapine
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