Acetaminophen And Codeine and Oliceridine: 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
Oliceridine
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 are opioid pain relievers. Codeine (combined with acetaminophen) and oliceridine (Olinvyk) each calm the nervous system. When you take them together, those calming effects add up. That can make you very sleepy, drop your blood pressure, and most importantly slow your breathing. In rare cases this can become dangerous.
There is also a smaller chance of something called serotonin syndrome, which can cause shaking, a fast heartbeat, sweating, and confusion. The good news is your care team can manage this by using the lowest doses that work and watching you closely. Never start, stop, or change these medicines on your own. Talk with your doctor or pharmacist first.
Effect: Additive CNS depression from two opioid agonists (codeine/acetaminophen plus oliceridine), raising risk of profound sedation, hypotension, respiratory depression, coma, and death. Both agents also carry serotonergic potential, so additive risk of serotonin syndrome exists.
- Mechanism: Additive pharmacodynamic CNS depression and additive serotonergic activity.
- Direction: Increased opioid/sedative effect. Note codeine is a CYP2D6 prodrug, but this interaction is pharmacodynamic, not metabolic.
- Evidence/onset: Theoretical; onset unspecified. Severity major.
- Management: Reserve for when alternatives are inadequate; use lowest effective doses and shortest duration. Start the added agent at a reduced dose and titrate to response. Monitor for respiratory depression, sedation, and serotonin syndrome; discontinue if suspected.
What happens
Increased risk of serotonin syndrome, an increased risk of hypotension, profound sedation, respiratory depression, coma and death
Interaction Deep Dive
When oliceridine (an opioid analgesic) is taken together with CNS depressants, additive pharmacological effects can heighten the likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing both agents together should be limited to patients for whom other treatment options prove insufficient. Should the clinician decide to combine a CNS depressant with an opioid analgesic, the lowest effective doses and shortest possible durations of joint use should be selected. For a patient already on an opioid analgesic, the CNS depressant should be started at a dose below that recommended when no opioid is present, then titrated according to clinical response. Conversely, when an opioid analgesic is added for a patient already taking another CNS depressant, the opioid analgesic should begin at a reduced initial dose and be titrated based on clinical response. Close observation for indications of respiratory depression and sedation is warranted. Furthermore, combining these drugs with serotonergic agents may provoke serotonin syndrome. Watch for signs and symptoms of serotonin syndrome and stop therapy if it is suspected1.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
How to manage this interaction
These two opioids can add together, so your care team will manage the combination carefully rather than avoid it automatically.
- Your doses may be lowered and individualized, often starting low and adjusting based on how you respond.
- Your team may use the shortest duration needed and monitor you more closely for heavy sedation, slowed breathing, or low blood pressure.
- Watch for serotonin syndrome signs: agitation, tremor, sweating, fast heartbeat, or confusion.
Keep taking both exactly as prescribed. Get emergency help for very slow breathing or extreme drowsiness, and ask your pharmacist or prescriber before making any changes.
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 likelihood of drug-related death when compared with using opioid analgesics by themselves. Given comparable pharmacological characteristics, it is reasonable to anticipate a comparable risk when other CNS depressant medications are used together with opioid analgesics 1.
b) In post marketing experience, instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used concurrently with serotonergic drugs 1.
Common questions
Can I take Acetaminophen And Codeine and Oliceridine together?
Combining codeine/acetaminophen with oliceridine adds two opioids together, raising the risk of dangerous sedation, slowed breathing, and low blood pressure, plus a smaller chance of serotonin syndrome. Your care team can manage this with low doses and close monitoring, so never change either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Oliceridine 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 Oliceridine interaction managed?
These two opioids can add together, so your care team will manage the combination carefully rather than avoid it automatically. Your doses may be lowered and individualized, often starting low and adjusting based on how you respond. Your team may use the shortest duration needed and monitor you more closely for heavy sedation, slowed breathing, or low blood pressure. Watch for serotonin syndrome s… 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 Oliceridine 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 (1)
- Product Information: OLINVYK(R) intravenous injection, oliceridine intravenous injection. Trevena Inc (per FDA), Chesterbrook, PA, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Oliceridine
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