Acetaminophen And Codeine and Trimipramine: 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
Trimipramine
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 trimipramine (an older antidepressant). These two can add up in a couple of ways. First, both can nudge your body's serotonin levels, and together they may raise the small chance of a reaction called serotonin syndrome (things like agitation, sweating, shaking, fast heartbeat, or fever).
Second, both can slow down your gut and bladder, so you might notice constipation or trouble urinating. Rarely, severe constipation can stall the bowel. The good news: this is mostly a theoretical concern, and your care team can manage it by watching you closely, especially when you first start or change doses.
Effect: Additive risk of serotonin syndrome and additive anticholinergic/opioid effects on GI and bladder motility (risk of urinary retention, severe constipation, potentially paralytic ileus).
Mechanism: Codeine has weak serotonergic activity; trimipramine is a serotonergic TCA with significant anticholinergic properties. Combined effects are additive on both serotonin tone and gut/bladder motility.
- Direction/magnitude: Increased effect; magnitude not quantified.
- Onset: Unspecified; highest vigilance at initiation and dose changes.
- Evidence: Theoretical.
- Management: Monitor for serotonin syndrome, urinary retention, and severe constipation; consider bowel regimen. Discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of paralytic ileus; increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like codeine are taken together with serotonergic agents. Furthermore, combining codeine with anticholinergic medications can heighten the likelihood of urinary retention and serious constipation, potentially progressing to paralytic ileus. When such combined therapy is required, watch the patient carefully for urinary retention, serious constipation, and any indications of serotonin syndrome1. throughout the start of therapy and whenever the dose is changed. Should serotonin syndrome be suspected, stop codeine 2.
Why it happens (mechanism)
Additive effects on gastric motility; additive serotonergic effects
How to manage this interaction
If your prescriber has you on both, keep taking them as directed. The concern is largely precautionary, and the main job is watching for warning signs.
- Watch for serotonin syndrome: agitation, confusion, sweating, tremor, shivering, muscle twitching, fast heartbeat, or fever.
- Watch your gut and bladder: significant constipation, belly pain or bloating, or trouble urinating.
- Report these promptly to your pharmacist or prescriber, especially in the first days or after any dose change.
- Your care team may monitor you more closely and adjust doses if needed. Do not stop either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Trimipramine together?
Taken together, codeine and trimipramine can add up to raise the chance of serotonin syndrome and of constipation or urinary retention, so watch for those symptoms and tell your care team right away; they can monitor and adjust as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Trimipramine 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 Trimipramine interaction managed?
If your prescriber has you on both, keep taking them as directed. The concern is largely precautionary, and the main job is watching for warning signs. Watch for serotonin syndrome: agitation, confusion, sweating, tremor, shivering, muscle twitching, fast heartbeat, or fever. Watch your gut and bladder: significant constipation, belly pain or bloating, or trouble urinating. Report these promptly t… 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 Trimipramine 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 Trimipramine
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