Acetaminophen And Codeine and Trifluoperazine: 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
Trifluoperazine
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 pain medicine contains codeine, an opioid, plus acetaminophen (Tylenol). Trifluoperazine is an older antipsychotic. Taken together, both can slow down your breathing and make you very drowsy or foggy. That combined slowing is the main concern.
These two can also both slow your gut and bladder. That can lead to bad constipation or trouble urinating, and in rare cases the bowel can nearly stop moving (called paralytic ileus). This concern is based mostly on how the drugs work rather than lots of case reports, but it is still taken seriously. Please don't stop either medicine on your own. Talk with your pharmacist or doctor, who can adjust doses and watch you closely so you stay safe.
Additive CNS and respiratory depression, plus additive reduction in GI/GU motility between codeine (an opioid; note codeine is a prodrug activated via CYP2D6, but this interaction is pharmacodynamic, not metabolic) and trifluoperazine (a phenothiazine with sedative and anticholinergic properties).
- Direction: increased sedation, respiratory depression; increased risk of urinary retention, severe constipation, and paralytic ileus.
- Mechanism: additive CNS depression; additive anticholinergic/opioid effects on gastric motility.
- Evidence: theoretical. Severity: major. Onset: unspecified.
- Management: reserve for patients lacking alternatives; use lowest effective dose and shortest duration; consider lowering codeine or trifluoperazine dose; monitor sedation, respiratory rate, urinary retention, and bowel function; consider prescribing naloxone.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Steer clear of using opioid cough medication products together with CNS depressants2. Combining codeine with CNS depressants should be limited to patients for whom other options are insufficient. When such combined use cannot be avoided, apply the lowest dose and the briefest duration required to reach therapeutic objectives. Furthermore, giving codeine alongside anticholinergics can raise the likelihood of urinary retention and/or severe constipation, potentially resulting in paralytic ileus. A reduced dose of either codeine or the CNS depressant should be considered, with close observation for urinary retention, decreased gastric motility, sedation, and respiratory depression. Should concurrent use be justified, prescribing naloxone for the emergency treatment of opioid overdose may be appropriate 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
The good news is your care team can manage this by tailoring your treatment.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either drug on your own.
- Your team may use the lowest effective dose for the shortest time, and may lower the dose of the codeine product or the trifluoperazine. Doses may be adjusted and individualized for you.
- They may monitor you more closely for heavy drowsiness, slow or shallow breathing, trouble urinating, and constipation.
- Tell your pharmacist or doctor right away about severe constipation, belly pain and bloating, inability to urinate, or trouble breathing.
- Your prescriber may also offer naloxone to keep on hand for emergencies.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, the rate of 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. Drug overdose deaths attributable to prescribed and above-prescribed doses of both drug classes also 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 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 receiving opioid analgesics who had a history of a benzodiazepine prescription, and rose by 3.86 fold in those with a current benzodiazepine prescription, compared with patients receiving opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as the daily doses of benzodiazepines increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related mortality compared with using opioid analgesics alone. Given their comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Trifluoperazine together?
Combining codeine (with acetaminophen) and trifluoperazine can add up to more sedation, slowed breathing, and a sluggish gut or bladder, so use only when needed at the lowest dose and let your care team monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Trifluoperazine 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 Trifluoperazine interaction managed?
The good news is your care team can manage this by tailoring your treatment. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not stop either drug on your own. Your team may use the lowest effective dose for the shortest time, and may lower the dose of the codeine product or the trifluoperazine. Doses may be adjusted and individualized for you. They may monitor you mor… 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 Trifluoperazine 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 Trifluoperazine
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