Acetaminophen And Codeine and Remifentanil: 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
Remifentanil
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 are opioid pain medicines. Your Tylenol with codeine contains codeine, and remifentanil is a strong opioid usually given during procedures or surgery. When two opioids are used together, their effects add up.
The main worry is that they can make you too sleepy and can slow your breathing too much. There is also a smaller, more theoretical concern about a reaction called serotonin syndrome (things like agitation, shivering, or a fast heartbeat). The good news is your care team knows about this. They can use the lowest doses needed and watch you closely, so this can be managed safely.
Effect: Additive CNS and respiratory depression from two mu-opioid agonists (codeine plus remifentanil), with a theoretical additive serotonergic risk (serotonin syndrome).
- Mechanism: Additive CNS depression; additive serotonergic effects. Pharmacodynamic, not PK. (Note: codeine is a CYP2D6 prodrug activated to morphine, but the concern here is additive PD opioid effect.)
- Severity/evidence: Major; theoretical. Onset unspecified.
- Management: Avoid opioid cough formulations with CNS depressants. Reserve non-cough codeine use to when alternatives are inadequate; use lowest dose, shortest duration. Monitor sedation, respiratory rate, and serotonin syndrome. Consider naloxone. Discontinue codeine if serotonin syndrome suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants2. Codeine products intended for uses other than cough should be paired with CNS depressants only in patients for whom other options are insufficient. When such combined use cannot be avoided, apply the lowest effective dose over the briefest period required to meet treatment objectives. A reduced dose of either codeine or the CNS depressant may be appropriate, with careful monitoring for sedation, respiratory depression, and indications of serotonin syndrome. Serotonin syndrome has also occurred when opioids are taken together with serotonergic agents. Should combined use be required, monitor the patient attentively, especially when starting therapy and when doses are being changed. Prescribing naloxone for emergency management of opioid overdose is worth considering. If serotonin syndrome is suspected, stop codeine 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Keep taking both exactly as prescribed and do not stop either on your own. Because both are opioids, your care team manages this by using the lowest effective dose for the shortest time and watching you closely.
- Your team may lower the dose of one medicine and monitor you for excess sleepiness and slowed breathing.
- They may also watch for serotonin syndrome (agitation, shivering, sweating, fast heartbeat, muscle twitching).
- Your prescriber may provide naloxone as an emergency safeguard.
- Call your pharmacist or doctor right away, or seek emergency help, if you feel very drowsy, confused, or have trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that emergency department visits linked to nonmedical use and involving both opioid analgesics and benzodiazepines rose significantly between 2004 and 2011, going from 11 to 34.2 per 100,000. Drug overdose fatalities attributable to prescribed and higher than prescribed doses of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, while overdose deaths involving benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose fatalities associated with dispensing both opioid analgesics and benzodiazepines was 10 times greater than dispensing opioid analgesics by themselves (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study using data spanning 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold among patients receiving opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold in those with a current benzodiazepine prescription, when compared with patients taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death compared with using opioid analgesics alone. Given comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
e) Instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used together with serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Remifentanil together?
Combining codeine with remifentanil stacks two opioids, raising the risk of heavy sedation and slowed breathing (and, in theory, serotonin syndrome). Your care team can manage this with the lowest doses, close monitoring, and possibly naloxone on hand. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Remifentanil 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 Remifentanil interaction managed?
Keep taking both exactly as prescribed and do not stop either on your own. Because both are opioids, your care team manages this by using the lowest effective dose for the shortest time and watching you closely. Your team may lower the dose of one medicine and monitor you for excess sleepiness and slowed breathing. They may also watch for serotonin syndrome (agitation, shivering, sweating, fast he… 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 Remifentanil 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 (4)
- 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.
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Remifentanil
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