Alfentanil 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
Alfentanil
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 are opioids. Your acetaminophen with codeine is a pain reliever, and alfentanil is a strong opioid usually used during procedures or in the hospital. When two opioids are used together, their calming effects on the brain add up. That can make you very sleepy and, more seriously, can slow your breathing too much.
There is also a smaller chance of a condition called serotonin syndrome (things like agitation, fast heartbeat, sweating, or shakiness). The good news is that your care team knows how to handle this. They can use the lowest doses needed and watch you closely, so please keep taking things exactly as prescribed and share any concerns.
Effect: Additive CNS and respiratory depression, plus a theoretical additive serotonergic risk (serotonin syndrome), when combining acetaminophen/codeine with alfentanil (two opioids).
- Mechanism: Additive mu-opioid CNS depression; both agents carry serotonergic potential.
- Direction/magnitude: Enhanced sedation and hypoventilation; magnitude not quantified.
- Onset: Unspecified; risk highest at initiation and dose changes.
- Evidence: Theoretical, severity rated major.
- Management: Reserve concomitant use for when alternatives are inadequate; use lowest effective dose and shortest duration; consider reducing dose of codeine or the other agent. Monitor for sedation, respiratory depression, and serotonin syndrome. Consider prescribing naloxone. Discontinue codeine if serotonin syndrome is suspected.
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 depressants2. 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 the CNS depressant and closely monitor for sedation, respiratory depression, and signs and symptoms of serotonin syndrome. Additionally, concomitant use of opioids with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Consider prescribing naloxone for the emergency treatment of opioid overdose. Discontinue codeine if serotonin syndrome is suspected 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Both drugs are opioids, so your care team will manage this carefully rather than combining them casually.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not adjust doses on your own.
- Your team may use the lowest effective dose for the shortest time, and one dose may need to be adjusted and individualized by them.
- They may monitor you more closely for heavy sedation, slowed breathing, or serotonin symptoms (agitation, fast heartbeat, sweating, tremor), especially when starting or changing doses.
- Ask your pharmacist or prescriber whether naloxone is appropriate to have on hand.
- Seek urgent help for very slow or shallow breathing or extreme drowsiness.
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 that occurred between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly, going from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths caused by benzodiazepines rose significantly from 18% to 31% 2.
b) A prospective cohort study reported that the rate of overdose deaths associated with dispensing both opioid analgesics and benzodiazepines was 10 times greater than that seen with dispensing opioid analgesics alone (7 versus 0.7 per 10,000 person years) 2.
c) In a cohort study drawing on data from 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold among patients using opioid analgesics who had a prior benzodiazepine prescription, and rose by 3.86 fold among 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 Alfentanil and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with alfentanil (both opioids) adds up their sedating effects and can dangerously slow breathing, with a smaller risk of serotonin syndrome. Use only under close medical supervision at the lowest needed doses, and get emergency help for very slow breathing or extreme drowsiness. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Alfentanil 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 Alfentanil and Acetaminophen And Codeine interaction managed?
Both drugs are opioids, so your care team will manage this carefully rather than combining them casually. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not adjust doses on your own. Your team may use the lowest effective dose for the shortest time, and one dose may need to be adjusted and individualized by them. They may monitor you more closely for heavy sedation,… 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 Alfentanil 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 (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
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