Aripiprazole 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
Aripiprazole
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 is an opioid pain reliever, and aripiprazole (Abilify) works in the brain to steady mood and thinking. Both can slow down your brain and calm your body. When taken together, that calming effect can add up, so you might feel more sleepy, dizzy, or foggy. In rare cases, breathing can slow down too much, which is why doctors take this seriously.
The good news is your care team can manage this. They may use the lowest dose needed for the shortest time and keep a close eye on how you feel. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor, and let them know right away if you feel very drowsy or short of breath.
Effect: Additive CNS and respiratory depression when codeine (with acetaminophen) is combined with aripiprazole.
Mechanism: Pharmacodynamic additive CNS depression. Codeine is an opioid prodrug activated to morphine via CYP2D6, but the concern here is PD (additive sedation), not a PK interaction.
- Direction: Increased sedation, hypotension, respiratory depression risk.
- Onset: Unspecified.
- Evidence: Theoretical; extrapolated from opioid plus CNS-depressant data.
- Management: Reserve for when alternatives are inadequate; use lowest effective dose and shortest duration; monitor for sedation/respiratory depression; consider naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Avoid concomitant use of opioid cough medication formulations and CNS depressants. Concomitant use of opioid analgesics with benzodiazepines has been associated with increased rates of emergency department visits and fatal overdose2. Concomitant use of codeine with CNS depressants can 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, consider prescribing naloxone for the emergency treatment of opioid overdose 341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is usually reserved for when other options aren't enough, so here is what your team typically does:
- Uses the lowest dose and shortest duration that works for you.
- May adjust and individualize the dose of the codeine product or aripiprazole to your needs.
- Monitors you more closely for heavy drowsiness or slowed breathing.
- May prescribe naloxone as a safety backup.
Tell your pharmacist or doctor if you feel unusually sleepy, confused, dizzy, or short of breath.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
4 reports — tap to read
a) In a study, the rate of emergency department visits related to nonmedical use that took place between 2004 and 2011 and that 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 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 seen with dispensing of opioid analgesics alone (7 versus 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 using 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 using opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths increased 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 their 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 Aripiprazole and Acetaminophen And Codeine together?
Combining Tylenol with Codeine and aripiprazole can add up to cause too much sedation and slowed breathing, so use the lowest dose for the shortest time and watch closely for drowsiness. Check with your pharmacist or doctor before making any changes. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Aripiprazole 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 Aripiprazole and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. This combination is usually reserved for when other options aren't enough, so here is what your team typically does: Uses the lowest dose and shortest duration that works for you. May adjust and individualize the dose of the codeine product or aripiprazole to your needs. Monitors you more closely for heavy drowsiness… 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 Aripiprazole 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 Aripiprazole
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