Clomipramine 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
Clomipramine
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.
Your pain medicine (codeine, combined with acetaminophen) and your clomipramine (Anafranil) can add up in two ways when taken together. First, both can raise serotonin, a brain chemical. Too much can cause serotonin syndrome, with symptoms like agitation, a fast heartbeat, sweating, shivering, or muscle twitching. Second, both can slow the gut and bladder, which can lead to serious constipation, trouble urinating, or in rare cases the bowel nearly stopping (paralytic ileus).
This is a theoretical concern, not a sure thing. The good news is your care team can manage it by watching you closely, especially when starting or changing doses. Don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive risk of serotonin syndrome and of reduced GI/bladder motility (severe constipation, urinary retention, potentially paralytic ileus).
Mechanism: Additive serotonergic activity (codeine has weak serotonergic effect; clomipramine potently blocks serotonin reuptake) plus additive slowing of gastric motility (opioid effect combined with clomipramine's anticholinergic activity).
- Direction: Additive PD interaction, not a PK/enzyme change.
- Onset: Unspecified; watch during initiation and dose titration.
- Evidence: Theoretical.
- Severity: Major.
- Management: Monitor for serotonin syndrome, 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
If both medicines are prescribed together, keep taking them as directed. Your care team can manage this interaction by monitoring you more closely, especially when starting or adjusting doses.
- Watch for serotonin syndrome: agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching or stiffness. Get help promptly if these appear.
- Watch your gut and bladder: report severe constipation, belly pain and bloating, or trouble urinating.
- Your doses may be adjusted and individualized by your care team.
- Don't start, stop, or change either medicine on your own. Ask your pharmacist or prescriber if you have questions.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Clomipramine and Acetaminophen And Codeine together?
Taking codeine with clomipramine can add up to cause serotonin syndrome or serious constipation and urinary problems, so watch for those symptoms and stay in touch with your care team, especially when doses change. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Clomipramine 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 Clomipramine and Acetaminophen And Codeine interaction managed?
If both medicines are prescribed together, keep taking them as directed. Your care team can manage this interaction by monitoring you more closely, especially when starting or adjusting doses. Watch for serotonin syndrome: agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching or stiffness. Get help promptly if these appear. Watch your gut and bladder: report severe constipati… 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 Clomipramine 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 Clomipramine
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