Cyproheptadine 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
Cyproheptadine
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 here is acetaminophen with codeine, and the other medicine is cyproheptadine, an antihistamine. Both can slow down your gut and both can make you sleepy, so taking them together may add up.
Two things to watch for: your bowels may slow too much (leading to bad constipation or trouble emptying your bladder), and you may feel extra drowsy or foggy. This concern is based on how the drugs work rather than strong studies, so it does not mean it will happen. Please don't stop either medicine on your own. Just let your pharmacist or doctor know you take both, and tell them right away if you feel very constipated, can't pass urine, or feel unusually sleepy. Your care team can manage this.
Effect: Additive risk of reduced GI motility (constipation, urinary retention, potential paralytic ileus) and additive CNS depression.
Mechanism: Cyproheptadine has anticholinergic activity that compounds codeine's opioid-mediated slowing of gastric motility; its sedating antihistamine action adds to codeine's CNS depression. Codeine is a CYP2D6 prodrug, but this is a pharmacodynamic (additive), not pharmacokinetic, interaction.
- Direction: Increased effect (additive).
- Severity/Evidence: Major severity; evidence theoretical.
- Onset: Unspecified.
- Monitoring: Watch for constipation, urinary retention, reduced bowel sounds/ileus, and excess sedation. Dose may need individualization by the care team.
What happens
An increased risk of paralytic ileus and an increased risk of CNS depression
Interaction Deep Dive
Concomitant use of codeine with cyproheptadine (anticholinergic agent) may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Hence if coadministered, monitor patients for signs of urinary retention or reduced gastric motility1. Concomitant use of cyproheptadine (antihistamine) may have additive effects with CNS depressants, such s codeine which may increase the risk of CNS depression 2.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
The good news is your care team can manage this by watching you a bit more closely and tailoring your doses if needed.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Watch for and report severe constipation, a bloated or painful belly, or trouble passing urine.
- Also report feeling unusually drowsy, confused, or hard to wake.
- Ask your pharmacist about staying hydrated and steps that help with constipation.
Your team may monitor your bowel and bladder function and adjust doses to keep you comfortable and safe.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Cyproheptadine and Acetaminophen And Codeine together?
Taking acetaminophen/codeine with cyproheptadine can add up to worse constipation, urinary retention, and drowsiness, so keep both as prescribed but tell your care team and report severe constipation, trouble urinating, or heavy sedation. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyproheptadine 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 Cyproheptadine and Acetaminophen And Codeine interaction managed?
The good news is your care team can manage this by watching you a bit more closely and tailoring your doses if needed. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Watch for and report severe constipation, a bloated or painful belly, or trouble passing urine. Also report feeling unusually drowsy, confused, or hard to wake. Ask your pharmacist about staying h… 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 Cyproheptadine 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: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Product Information: Cyproheptadine HCl oral solution, cyproheptadine HCl oral solution. Lannett Company Inc (per DailyMed), Philadelphia, PA, 2017.
Keep reading about Acetaminophen And Codeine
Keep reading about Cyproheptadine
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