Desipramine 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
Desipramine
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 desipramine (Norpramin, used for depression or nerve pain). Both can affect the body in ways that add up. Together they can raise the chance of a rare but serious reaction called serotonin syndrome, with signs like agitation, fast heartbeat, sweating, shakiness, or confusion. This combo can also slow down your gut and bladder, leading to bad constipation or trouble urinating.
The good news is your care team can manage this. They'll usually keep an eye on you, especially when you first start or change a dose. If anything feels off, call your pharmacist or doctor right away.
Effect: Additive risk of serotonin syndrome plus additive reduction in GI/GU motility (severe constipation, urinary retention, potential paralytic ileus).
- Mechanism: Codeine has weak serotonergic activity; desipramine (TCA) inhibits serotonin/norepinephrine reuptake and carries anticholinergic effects, compounding opioid-induced slowed motility.
- Direction/magnitude: Additive PD effects; magnitude not quantified.
- Onset: Unspecified; watch at initiation and dose changes.
- Evidence: Theoretical.
- Management: Monitor for serotonin syndrome (autonomic instability, neuromuscular signs, mental status change), urinary retention, and severe constipation. Discontinue codeine if serotonin syndrome is suspected; dose may be individualized by the care team.
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 interaction is usually manageable with monitoring.
- Your team may watch you more closely when you start either drug or change a dose.
- Doses may be adjusted and individualized by your care team.
- Tell your doctor or pharmacist if you notice agitation, a racing heart, sweating, shivering, muscle twitching, or confusion, these can signal serotonin syndrome.
- Also report severe constipation, belly pain and bloating, or trouble urinating.
If serotonin syndrome is suspected, the codeine may need to be stopped, so seek care promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Desipramine and Acetaminophen And Codeine together?
Taking codeine with desipramine can add up to raise the risk of serotonin syndrome and of severe constipation or urinary retention, so watch for those symptoms and stay in touch with your care team. This is manageable with monitoring, and dosing can be tailored by your doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Desipramine 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 Desipramine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This interaction is usually manageable with monitoring. Your team may watch you more closely when you start either drug or change a dose. Doses may be adjusted and individualized by your care team. Tell your doctor or pharmacist if you notice agitation, a racing heart, sweating, shivering, muscle twitching, or conf… 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 Desipramine 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 Desipramine
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