Fluphenazine 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
Fluphenazine
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, and you're also taking fluphenazine, a medicine for mental health conditions. Both can slow down your brain and breathing, and both can slow your gut. Taken together, they can add up. That means you might feel more drowsy or foggy, breathe more slowly, or have trouble going to the bathroom, including very bad constipation or even a stalled gut.
This concern is based on how these drugs work rather than lots of case reports, but it's worth taking seriously. The good news is your care team can manage it by using the lowest helpful dose and watching you closely. Please don't stop either medicine on your own, just talk with your pharmacist or doctor.
Effect: Additive CNS and respiratory depression plus additive reduction in gastric motility, raising risk of sedation, hypoventilation, urinary retention, severe constipation, and paralytic ileus.
Mechanism: Overlapping CNS depressant effects; codeine's opioid and fluphenazine's anticholinergic actions additively reduce GI motility. Codeine is a prodrug activated via CYP2D6, but this is a pharmacodynamic (not metabolic) interaction.
Evidence: Theoretical; severity major; onset unspecified.
- Reserve combined use for patients without adequate alternatives.
- Use lowest effective dose, shortest duration.
- Monitor sedation, respiratory rate, bowel/bladder function.
- Consider prescribing naloxone.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants2. Reserve the concomitant use of codeine 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. Additionally, coadministration of codeine with anticholinergics may increase the risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Consider using a lower dose of codeine or the CNS depressant and closely monitor for urinary retention, reduced gastric motility, sedation, and respiratory depression. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
If your prescriber has you on both, the interaction can usually be managed safely.
- Keep taking both as prescribed unless your care team tells you otherwise.
- Your team may use the lowest effective dose of the codeine or the fluphenazine for the shortest time needed, and the doses may be adjusted and individualized for you.
- They may monitor you more closely for drowsiness, slow breathing, trouble urinating, and constipation.
- Ask whether naloxone (opioid rescue) is appropriate to have on hand.
Call your pharmacist or doctor right away if you feel very sleepy, breathe slowly, can't pass urine, or stop having bowel movements.
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 linked to nonmedical use that occurred between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributed 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 attributed 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 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 among 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, compared with patients taking 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 the similar pharmacological properties, it is reasonable to anticipate comparable risk when other CNS depressant drugs are used concurrently with opioid analgesics 34.
Common questions
Can I take Fluphenazine and Acetaminophen And Codeine together?
Combining codeine with fluphenazine can add up to more sedation, slowed breathing, and slowed gut function, so use the lowest dose needed and watch for drowsiness, constipation, or trouble urinating. Don't change anything on your own, check with your pharmacist or doctor. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluphenazine 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 Fluphenazine and Acetaminophen And Codeine interaction managed?
If your prescriber has you on both, the interaction can usually be managed safely. Keep taking both as prescribed unless your care team tells you otherwise. Your team may use the lowest effective dose of the codeine or the fluphenazine for the shortest time needed, and the doses may be adjusted and individualized for you. They may monitor you more closely for drowsiness, slow breathing, trouble ur… 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 Fluphenazine 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
Keep reading about Acetaminophen And Codeine
Keep reading about Fluphenazine
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