Dihydrocodeine 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
Dihydrocodeine
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 your medicines are opioid pain relievers. Your Tylenol with codeine contains codeine, and the other one is dihydrocodeine. Taking two opioids together stacks their effects, so they can slow your breathing, make you very sleepy or dizzy, and lower your blood pressure more than either one alone. In rare cases this can be dangerous.
The good news is your care team can manage this. They may use the lowest dose for the shortest time and watch you closely. Please don't stop or change anything on your own. Call your doctor or pharmacist right away if you notice heavy drowsiness, confusion, or slow or shallow breathing.
Effect: Additive CNS and respiratory depression from combining two opioids (codeine plus dihydrocodeine), with a theoretical additive serotonergic risk. Risk includes hypotension, profound sedation, respiratory depression, coma, and death.
Mechanism: Additive mu-opioid and CNS depressant pharmacodynamics; both agents are serotonergic opioids. This is a PD interaction, not primarily PK.
Evidence: Theoretical; severity rated major; onset unspecified.
- Reserve co-use for when alternatives are inadequate.
- Use lowest effective dose, shortest duration; consider lowering one agent.
- Monitor for sedation, respiratory depression, serotonin syndrome.
- Consider prescribing naloxone.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of dihydrocodeine with CNS depressants can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve the concomitant use of dihydrocodeine 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 dihydrocodeine or the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome1. 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 2.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
These are both opioids, so the main goal is avoiding too much sedation and slowed breathing.
- Keep taking both only as prescribed and do not adjust doses yourself.
- Your care team typically reserves this combination for when other options aren't enough, and may use the lowest dose for the shortest time. The dose may need to be individualized by your team, and they may monitor you more closely.
- Ask your prescriber or pharmacist whether a naloxone rescue kit is right for you.
- Seek help urgently for extreme drowsiness, confusion, or slow, shallow breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Observational research has shown that using opioid analgesics together with benzodiazepines raises the risk of death related to the drugs when compared with using opioid analgesics by themselves. Given their comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant medications are combined with opioid analgesics 2.
b) Instances of serotonin syndrome, a condition that can be life-threatening, have been described when opioids are used together with serotonergic drugs 2.
Common questions
Can I take Dihydrocodeine and Acetaminophen And Codeine together?
Codeine and dihydrocodeine are both opioids, so combining them adds up their sedation and breathing-slowing effects; use only as prescribed at the lowest dose, watch for heavy drowsiness or slow breathing, and ask about a naloxone kit. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dihydrocodeine 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 Dihydrocodeine and Acetaminophen And Codeine interaction managed?
These are both opioids, so the main goal is avoiding too much sedation and slowed breathing. Keep taking both only as prescribed and do not adjust doses yourself. Your care team typically reserves this combination for when other options aren't enough, and may use the lowest dose for the shortest time. The dose may need to be individualized by your team, and they may monitor you more closely. Ask y… 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 Dihydrocodeine 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: TREZIX(TM) oral capsules, acetaminophen caffeine dihydrocodeine bitartrate oral capsules. WraSer Pharmaceuticals (per DailyMed), Ridgeland, MS, 2016. DailyMed
- Product Information: SYNALGOS(R)-DC oral capsules, aspirin, caffeine, dihydrocodeine bitartrate oral capsules. Sun Pharmaceuticals Industries Inc (per FDA), Cranbury, NJ, 2023. DailyMed
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