Acetaminophen And Codeine and Benzhydrocodone: 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
Benzhydrocodone
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.
Both of these medicines contain opioids. Your Tylenol with codeine has codeine in it, and benzhydrocodone is an opioid too (it turns into hydrocodone in your body). Taking them together means you are getting two opioids at once, which can add up and slow down your breathing and make you very sleepy. There is also a smaller, more theoretical chance of a reaction called serotonin syndrome, which can cause things like shakiness, a fast heartbeat, agitation, or fever.
The good news: your care team can manage this. They may use the lowest dose for the shortest time, or pick a different medicine. Please talk with your doctor or pharmacist before combining these two.
Effect: Additive CNS and respiratory depression from two opioids (codeine plus benzhydrocodone, a prodrug metabolized to hydrocodone), with a theoretical additive serotonergic risk (serotonin syndrome).
- Mechanism: Additive mu-opioid CNS depression; additive serotonergic activity.
- Direction: Increased opioid effect and toxicity risk.
- Onset: Unspecified. Evidence: Theoretical. Severity: Major.
- Management: Avoid where possible; reserve for patients lacking adequate alternatives. If combined, use lowest effective dose and shortest duration, consider dose reduction of either agent, monitor for sedation, respiratory depression, and serotonin syndrome. Discontinue the opioid if serotonin syndrome is suspected; consider prescribing naloxone.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants1. Also, concomitant use of HYDROcodone, with serotonergic drugs has resulted in serotonin syndrome. Reserve the concomitant use of non-cough HYDROcodone 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 HYDROcodone or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. Discontinue HYDROcodone if serotonin syndrome is suspected 234. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 56.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
This combination is usually avoided because both products are opioids and the effects stack. Keep taking your medicines as prescribed, but raise this overlap with your prescriber or pharmacist promptly.
- Your care team may choose an alternative, or if both are needed, use the lowest dose for the shortest time and adjust doses individually.
- They may monitor you more closely for heavy sedation, slowed or shallow breathing, and signs of serotonin syndrome (agitation, sweating, tremor, fast heartbeat, fever).
- Your team may also prescribe naloxone as an emergency rescue.
- Get emergency help for very slow or difficult breathing or extreme drowsiness.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Benzhydrocodone together?
Both drugs are opioids, so combining them raises the risk of dangerous sedation and slowed breathing (plus a theoretical serotonin syndrome risk). Do not combine them without talking to your prescriber or pharmacist, who can adjust the plan and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Benzhydrocodone 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 Acetaminophen And Codeine and Benzhydrocodone interaction managed?
This combination is usually avoided because both products are opioids and the effects stack. Keep taking your medicines as prescribed, but raise this overlap with your prescriber or pharmacist promptly. Your care team may choose an alternative, or if both are needed, use the lowest dose for the shortest time and adjust doses individually. They may monitor you more closely for heavy sedation, slowe… 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 Acetaminophen And Codeine or Benzhydrocodone 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 (6)
- Product Information: VITUZ(R) oral solution, hydrocodone bitartrate chlorpheniramine maleate oral solution. Hawthorn Pharmaceuticals, Inc. (per FDA), Morristown, NJ, 2017.
- Product Information: ZOHYDRO(R) ER oral extended-release capsules, hydrocodone bitartrate oral extended-release capsules. Pernix Therapeutics, LLC. (per FDA), Morristown, NJ, 2016. DailyMed
- Product Information: NORCO 5/325 oral tablets, hydrocodone bitartrate acetaminophen oral tablets. Allergan USA, Inc. (per DailyMed), Irvine, CA, 2016.
- Product Information: VANTRELA(TM) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Teva Pharmaceuticals USA, Inc (per manufacturer), North Wales, PA, 2017. DailyMed
- Product Information: HYSINGLA(R) ER oral extended-release tablets, hydrocodone bitartrate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: APADAZ(R) oral tablets, benzhydrocodone acetaminophen oral tablets. Zevra Therapeutics, Inc. (per FDA), Celebration, FL, 2023. DailyMed
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