Acetaminophen And Codeine and Imipramine: 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
Imipramine
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 medicine) along with imipramine (a tricyclic antidepressant). When these two are taken together, there are two things to watch for.
First, both can raise levels of a brain chemical called serotonin. Rarely, too much can cause serotonin syndrome, with symptoms like agitation, fast heartbeat, shivering, sweating, or muscle twitching. Second, both can slow the gut and bladder, which can lead to bad constipation, trouble urinating, and in rare cases a stalled bowel. This is a theoretical concern, not a sure thing. Your care team can manage it by watching you closely, especially when you start or change doses. Call them if you feel unwell.
Additive PD interaction. Codeine (a serotonergic opioid) combined with imipramine (a serotonergic, strongly anticholinergic TCA) yields two additive risks:
- Serotonin syndrome from combined serotonergic activity.
- Paralytic ileus / urinary retention from additive anticholinergic and opioid-induced GI hypomotility (severe constipation).
Direction: increased effect/toxicity risk. Severity: major. Evidence: theoretical. Onset: unspecified.
Management: If co-prescribed, monitor closely at initiation and dose changes for constipation, urinary retention, and neuromuscular/autonomic signs of serotonin toxicity. Consider bowel regimen. Discontinue codeine if serotonin syndrome is suspected. Note codeine is a CYP2D6 prodrug, but the concern here is additive PD, not PK.
What happens
Increased risk of paralytic ileus; increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids such as codeine are taken together with serotonergic agents. Combining codeine with anticholinergic medications can also heighten the likelihood of urinary retention and severe constipation, potentially progressing to paralytic ileus. When these combinations cannot be avoided, watch the patient carefully for urinary retention, severe constipation, and any signs or symptoms of serotonin syndrome1 while therapy is being started and doses are being modified. 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
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your care team can manage this combination with monitoring.
- They may watch you more closely when you start either drug or change a dose.
- Doses may need to be adjusted and individualized by your care team.
- They may suggest steps to prevent constipation, such as fluids and fiber.
Call your pharmacist or doctor right away if you notice severe constipation, belly bloating or pain, trouble urinating, or agitation, sweating, shivering, fast heartbeat, or muscle twitching. These can be signs to act on quickly.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Imipramine together?
Taking acetaminophen/codeine with imipramine can add up to a higher risk of serotonin syndrome and severe constipation or bowel/urinary slowdown, so watch for those symptoms and stay in touch with your care team, especially at the start or with dose changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Imipramine 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 Imipramine interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your care team can manage this combination with monitoring. They may watch you more closely when you start either drug or change a dose. Doses may need to be adjusted and individualized by your care team. They may suggest steps to prevent constipation, such as fluids and fiber. Call your pharmacist or doctor right… 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 Imipramine 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 Imipramine
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