Acetaminophen And Codeine and Trifluperidol: 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
Trifluperidol
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.
Your medicine Tylenol with Codeine contains codeine, an opioid pain reliever that can slow your breathing and make you sleepy. Trifluperidol is an antipsychotic that also calms the nervous system. Taken together, these two effects can add up, so you may feel very drowsy, dizzy, or foggy, and in serious cases your breathing could slow down too much.
Please don't stop either medicine on your own. This combination is sometimes used when it's truly needed, but your care team will want to know you're on both. Tell your doctor or pharmacist so they can keep your doses as low as possible and watch you closely. That's how this is safely managed.
Effect: Additive CNS and respiratory depression from combining codeine (opioid, in the acetaminophen/codeine product) with trifluperidol (a butyrophenone antipsychotic with sedative properties).
- Mechanism: Pharmacodynamic (additive CNS depression); no shared metabolic pathway required. Note codeine is a prodrug activated via CYP2D6, but this is a PD, not PK, interaction.
- Direction/magnitude: Increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Evidence: Theoretical; extrapolated from documented opioid plus CNS depressant harms.
- Onset: Unspecified.
- Management: Avoid unless alternatives inadequate; use lowest effective dose and shortest duration; monitor sedation and respiratory status; consider naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Opioid-based cough preparations should not be combined with CNS depressants. Taking opioid analgesics alongside benzodiazepines has been linked to higher rates of both emergency department visits and lethal overdose2. When codeine is used together with CNS depressants, there is an elevated risk of hypotension, respiratory depression, deep sedation, coma, and death. Prescribing these agents together should be limited to patients in whom other treatment approaches prove insufficient. Keep doses and treatment durations at the lowest level needed. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, prescribing naloxone for the emergency management of opioid overdose may be considered341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Your care team can manage this safely if both drugs are truly needed. Typically they will:
- Reserve this combination for when other options aren't enough.
- Use the lowest dose and shortest duration of the codeine product, the trifluperidol, or both.
- Monitor you closely for excess sedation and slowed breathing.
- Sometimes prescribe naloxone as an emergency rescue medicine.
What you should do: keep taking both exactly as prescribed, and don't change doses yourself. Tell your pharmacist or prescriber right away if you feel unusually sleepy, confused, dizzy, or short of breath. Avoid alcohol and other sedating medicines unless your team approves them.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) One study found that emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed doses and doses exceeding those prescribed of both drug classes likewise rose significantly from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths involving the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated with the dispensing of opioid analgesics alone (7 vs 0.7 per 10,000 person years) 2.
c) In a cohort study using data from 2004 to 2009, the risk of fatal overdose rose significantly by 2.33 fold in patients taking 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 and benzodiazepines together raises the risk of drug-related mortality relative to using opioid analgesics alone. Given the comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Trifluperidol together?
Combining codeine with trifluperidol adds up their sedating effects and can dangerously slow breathing; keep taking both only as prescribed and tell your doctor or pharmacist so they can use the lowest doses and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Trifluperidol 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 Trifluperidol interaction managed?
Your care team can manage this safely if both drugs are truly needed. Typically they will: Reserve this combination for when other options aren't enough. Use the lowest dose and shortest duration of the codeine product, the trifluperidol, or both. Monitor you closely for excess sedation and slowed breathing. Sometimes prescribe naloxone as an emergency rescue medicine. What you should do: keep tak… 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 Trifluperidol 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 Trifluperidol
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist