Acetaminophen And Codeine and Quetiapine: 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
Quetiapine
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 quetiapine (Seroquel). Both of these can make you very sleepy and can slow your breathing. Taken together, those effects can add up, so you may feel more drowsy, foggy, or dizzy than usual.
Both drugs can also slow down your gut. That can cause bad constipation and, rarely, a serious blockage where the bowel stops moving. Please don't stop either medicine on your own. Instead, tell your doctor or pharmacist you take both. They can pick the lowest doses, watch you more closely, and keep you safe.
Effect: Additive CNS and respiratory depression plus additive reduction in GI motility, raising risk of severe constipation and paralytic ileus. Codeine (an opioid; note it is a prodrug requiring CYP2D6 activation to morphine, though the concern here is pharmacodynamic, not metabolic) combined with quetiapine, a sedating agent with anticholinergic properties.
- Mechanism: PD additivity (sedation, respiratory drive) and additive anticholinergic/opioid-mediated slowing of gut motility.
- Severity/Evidence: Major; theoretical.
- Management: Avoid if possible; if needed, use lowest effective opioid/CNS-depressant dose for shortest duration. Monitor sedation, respiratory rate, urinary retention, and bowel function. Consider naloxone access.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Refrain from using opioid cough medication products together with CNS depressants2. The combined use of codeine and CNS depressants should be limited to patients in whom other options are insufficient. When such combined use cannot be avoided, employ the smallest dose and briefest treatment period required to meet 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 may be considered, along with vigilant monitoring for urinary retention, decreased gastric motility, sedation, and respiratory depression. Should concurrent use be justified, prescribing naloxone for the emergency management of opioid overdose is worth considering 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
The safest option is to avoid using these together when a suitable alternative exists, so ask your care team whether both are truly needed. If both are needed, they can manage it:
- Use the lowest dose for the shortest time that controls your pain.
- Your team may monitor you more closely for heavy drowsiness, slowed breathing, constipation, and trouble urinating.
- Your doses may be adjusted and individualized by your prescriber.
- They may also prescribe naloxone as an emergency backup.
Keep taking both as prescribed, and call your pharmacist or doctor before making any changes. Seek urgent help for very slow breathing or severe belly pain.
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 occurred 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 likewise increased 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 the rate 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 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 and benzodiazepines together increases 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 together with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Quetiapine together?
Combining codeine with quetiapine can add up to more sedation, slowed breathing, and severe constipation, so use the lowest doses needed 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 Quetiapine 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 Quetiapine interaction managed?
The safest option is to avoid using these together when a suitable alternative exists, so ask your care team whether both are truly needed. If both are needed, they can manage it: Use the lowest dose for the shortest time that controls your pain. Your team may monitor you more closely for heavy drowsiness, slowed breathing, constipation, and trouble urinating. Your doses may be adjusted and indivi… 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 Quetiapine 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 Quetiapine
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