Chlorpheniramine 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
Chlorpheniramine
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.
Your pain medicine (codeine with acetaminophen) and your allergy or cold medicine (chlorpheniramine) can add up in two ways. Both can slow down your gut, so together they may cause worse constipation and trouble emptying your bladder. In rare cases, very bad constipation can stall the bowel completely.
Also, codeine can slightly raise a brain chemical called serotonin, so there is a small, mostly theoretical chance of something called serotonin syndrome (things like agitation, shakiness, sweating, or a fast heartbeat). This is not common, and your care team can manage it. If you ever feel these things, reach out to your pharmacist or doctor right away.
Additive pharmacodynamic interaction. Codeine (an opioid) plus chlorpheniramine (a sedating antihistamine with significant anticholinergic activity) produces additive reductions in GI and bladder motility, increasing risk of severe constipation, urinary retention, and potentially paralytic ileus. Codeine also carries a theoretical additive serotonergic risk, so serotonin syndrome is possible though unlikely.
- Direction: increased adverse effects (additive), not a metabolic clearance change.
- Evidence: theoretical; severity: major; onset: unspecified.
- Monitor: bowel function, urinary retention, and serotonin syndrome signs, especially at initiation and dose changes. Discontinue codeine if serotonin syndrome is suspected.
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. Because both can slow the gut, your team may watch you more closely and tailor doses, particularly when starting or adjusting either drug.
- Watch for severe constipation, no bowel movements, belly pain or swelling, or trouble urinating.
- Watch for serotonin syndrome signs: agitation, confusion, shivering, sweating, muscle twitching, or a racing heart.
- Staying hydrated and active can help with constipation.
Report any of these symptoms to your pharmacist or prescriber promptly, and ask before combining with other sedating or anticholinergic products.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Chlorpheniramine and Acetaminophen And Codeine together?
Taking codeine with chlorpheniramine can add up to worse constipation and urinary retention (rarely a stalled bowel), plus a small theoretical risk of serotonin syndrome. Keep taking both as prescribed, watch for these symptoms, and contact your pharmacist or doctor if they appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Chlorpheniramine 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 Chlorpheniramine and Acetaminophen And Codeine interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because both can slow the gut, your team may watch you more closely and tailor doses, particularly when starting or adjusting either drug. Watch for severe constipation, no bowel movements, belly pain or swelling, or trouble urinating. Watch for serotonin syndrome signs: agitation, confusion, shivering, sweating, m… 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 Chlorpheniramine 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 Chlorpheniramine
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