Cyclobenzaprine and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Cyclobenzaprine
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.
Both of these medicines can slow you down. Codeine (a pain reliever, combined here with acetaminophen) and cyclobenzaprine (a muscle relaxer) each cause drowsiness. Taken together, that sleepy, foggy feeling can add up, and in some cases breathing can slow too much. Both can also slow the gut, which may lead to bad constipation or trouble passing urine.
There is also a small chance of something called serotonin syndrome, which can cause shakiness, a fast heart, sweating, or confusion. The good news is your care team can manage this by choosing the right dose and keeping an eye on how you feel. Never stop or change either medicine on your own, just talk with your pharmacist or doctor.
Additive CNS and respiratory depression, additive anticholinergic/gut-slowing effects, and additive serotonergic effects when acetaminophen/codeine is combined with cyclobenzaprine.
- Direction: pharmacodynamic additive effect (not a CYP2D6 activation issue); expect enhanced sedation, hypoventilation, constipation/paralytic ileus, urinary retention, and possible serotonin syndrome.
- Evidence: theoretical; severity major; onset unspecified.
- Management: reserve for when alternatives are inadequate; use lowest effective dose and shortest duration; consider reducing codeine or cyclobenzaprine dose; monitor for sedation, respiratory depression, constipation, urinary retention, and serotonin syndrome. Consider prescribing naloxone.
What happens
Increased risk of paralytic ileus; increased risk of respiratory and CNS depression; increased risk of serotonin syndrome
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants3. Reserve the concomitant use of non-cough codeine products and CNS depressants to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. Consider using a lower dose of codeine or cyclobenzaprine and closely monitor for urinary retention, severe constipation, signs and symptoms of serotonin syndrome, sedation, and respiratory depression 1. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 2.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression; additive serotonergic effects
How to manage this interaction
If your prescriber has you on both, they are usually reserving this combination for when other options are not enough, and that is manageable with the right plan.
- Keep taking both exactly as prescribed unless your care team tells you otherwise.
- Your team may use the lowest dose for the shortest time and may adjust and individualize either drug's dose.
- They may monitor you more closely for heavy sedation, slowed breathing, severe constipation, trouble urinating, or serotonin syndrome (agitation, fast heartbeat, sweating, shakiness).
- Ask whether naloxone (emergency opioid rescue) is right to have on hand.
- Call your pharmacist or doctor about any of these warning signs.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Cyclobenzaprine and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with cyclobenzaprine adds up sedation, breathing slowdown, gut and bladder slowing, and a small serotonin syndrome risk; take both only as prescribed and let your care team use the lowest dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cyclobenzaprine 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 Cyclobenzaprine and Acetaminophen And Codeine interaction managed?
If your prescriber has you on both, they are usually reserving this combination for when other options are not enough, and that is manageable with the right plan. Keep taking both exactly as prescribed unless your care team tells you otherwise. Your team may use the lowest dose for the shortest time and may adjust and individualize either drug's dose. They may monitor you more closely for heavy se… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Cyclobenzaprine 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 (3)
- 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
- US Food and Drug Administration (FDA): Drug Safety Communications: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines; requires its strongest warning. US Food and Drug Administration (FDA). Silver Spring, MD. 2016.
Keep reading about Acetaminophen And Codeine
Keep reading about Cyclobenzaprine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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