Acetaminophen And Codeine and Triflupromazine: 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
Triflupromazine
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.
You've been given acetaminophen with codeine (a pain medicine that contains an opioid) along with triflupromazine (an older antipsychotic). Both of these can slow down your brain and your breathing. When you take them together, that calming effect can add up, and you may feel very drowsy, dizzy, or lightheaded. In more serious cases, breathing can slow down too much.
The good news is that your care team can manage this safely. They'll aim for the lowest dose for the shortest time and watch how you respond. Let your pharmacist or doctor know right away if you feel unusually sleepy, confused, or short of breath, and never add alcohol or other sedatives on your own.
Effect: Additive CNS and respiratory depression from combining codeine (opioid analgesic in the acetaminophen/codeine product) with triflupromazine (a sedating phenothiazine antipsychotic).
- Mechanism: Pharmacodynamic (additive CNS depression). No PK interaction implied; note codeine is a prodrug bioactivated by CYP2D6, but this interaction is PD, not enzyme-mediated.
- Direction/magnitude: Increased risk of hypotension, profound sedation, respiratory depression, coma, death.
- Onset: Unspecified. Evidence: Theoretical, but rated major.
- Management: Reserve for patients lacking alternatives; use lowest effective dose and shortest duration; monitor sedation and respiratory rate; consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Opioid cough preparations should not be taken together with CNS depressants. Data show that pairing opioid analgesics with benzodiazepines raises the frequency of emergency department visits as well as fatal overdoses2. When codeine is combined with CNS depressants, the likelihood of profound sedation, respiratory depression, hypotension, coma and death is elevated. Prescribing both agents together should be limited to patients whose alternative therapies prove insufficient. Both dose and treatment duration ought to be held to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should combined therapy be justified, prescribing naloxone for emergency management of opioid overdose may be appropriate341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Both medicines can calm the nervous system, so used together they may cause more sedation and slower breathing. Your care team knows how to handle this.
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change doses on your own.
- Your team may use the lowest dose for the shortest time and may monitor you more closely for drowsiness and breathing changes.
- Ask whether a naloxone rescue kit is appropriate for you.
- Avoid alcohol and other sedating products.
- Get help right away for severe sleepiness, confusion, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In one study, emergency department visits related to nonmedical use that took place between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and above-prescribed doses of both drug classes likewise increased significantly from 0.6 to 1.7 per 100,000, while overdose deaths caused by benzodiazepines rose significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths associated with dispensing both opioid analgesics and benzodiazepines was 10 times greater than that seen with dispensing of opioid analgesics on their own (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 among patients on opioid analgesics who had a prior 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 relative to using opioid analgesics by themselves. Given their comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are combined with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Triflupromazine together?
Taking acetaminophen/codeine with triflupromazine can add up to dangerous sedation and slowed breathing, so use the lowest dose for the shortest time and watch closely for drowsiness or breathing problems. Talk with your pharmacist or doctor about safe use and whether naloxone is right for you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Triflupromazine 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 Triflupromazine interaction managed?
Both medicines can calm the nervous system, so used together they may cause more sedation and slower breathing. Your care team knows how to handle this. Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Do not stop or change doses on your own. Your team may use the lowest dose for the shortest time and may monitor you more closely for drowsiness and breathing cha… 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 Triflupromazine 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 Triflupromazine
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