Butorphanol 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
Butorphanol
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.
Your medicine Tylenol with Codeine and butorphanol are both opioid pain relievers, but they don't work well together. Butorphanol is a mixed type of opioid, so it can actually block some of codeine's pain relief and even trigger uncomfortable withdrawal feelings.
At the same time, using two opioids can add up in your body. That can cause too much drowsiness, slowed breathing, very low blood pressure, or a rare but serious reaction called serotonin syndrome (agitation, fever, shakiness). The good news is your care team knows how to handle this. Usually they avoid combining them, but if both are truly needed they will use the lowest dose for the shortest time and watch you closely. Please talk with your pharmacist or doctor before combining them.
Effect: Combining codeine (a mu-opioid agonist prodrug) with butorphanol (a mixed agonist/antagonist) may reduce codeine's analgesic effect and precipitate withdrawal via competitive opioid receptor binding, while adding risk of serotonin syndrome and additive CNS/respiratory depression, hypotension, sedation, coma, and death.
- Mechanism: competitive opioid receptor binding; additive serotonergic and CNS depressant effects.
- Direction: reduced codeine efficacy plus increased toxicity risk.
- Evidence: theoretical; severity major; onset unspecified.
- Management: avoid combination; reserve for inadequate alternatives; minimize dose/duration; monitor closely at initiation and titration; d/c codeine if serotonin syndrome suspected; consider naloxone.
What happens
Reduced analgesic effect and/or precipitation of withdrawal symptoms, an increased risk of serotonin syndrome and an increased risk of hypotension, respiratory depression, profound sedation, coma, and death
Interaction Deep Dive
Avoid concomitant use of codeine with butorphanol (a serotonergic CNS depressant and a mixed opioid agonist/antagonist or a partial agonist opioid analgesic) as this may reduce the analgesic effect of codeine and may precipitate withdrawal symptoms, increase the risk for serotonin syndrome and may increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue codeine if serotonin syndrome is suspected and consider prescribing naloxone for the emergency treatment of opioid overdose1.
Why it happens (mechanism)
Competitive binding at opioid receptors; additive serotonergic effects; additive CNS depression
How to manage this interaction
Generally, this combination is avoided. Keep taking exactly what is prescribed, and do not start, stop, or change either drug on your own.
- If both are needed, your care team will use the lowest dose for the shortest time and individualize your plan.
- Expect closer monitoring, especially when starting or adjusting doses.
- Get urgent help for slow or shallow breathing, extreme drowsiness, fainting, or signs of serotonin syndrome (agitation, fever, muscle twitching, fast heartbeat).
- Ask your pharmacist or prescriber whether a naloxone rescue kit is right for you.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Butorphanol and Acetaminophen And Codeine together?
Codeine and butorphanol are usually avoided together because butorphanol can blunt codeine's pain relief and trigger withdrawal, while both opioids add up to dangerous sedation and breathing problems. Talk with your pharmacist or doctor before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Butorphanol 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 Butorphanol and Acetaminophen And Codeine interaction managed?
Generally, this combination is avoided. Keep taking exactly what is prescribed, and do not start, stop, or change either drug on your own. If both are needed, your care team will use the lowest dose for the shortest time and individualize your plan. Expect closer monitoring, especially when starting or adjusting doses. Get urgent help for slow or shallow breathing, extreme drowsiness, fainting, or… 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 Butorphanol 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 (1)
- Product Information: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Butorphanol
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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