Acetaminophen And Codeine and Olanzapine: 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
Olanzapine
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.
Both of these medicines can slow down your body. Codeine (in your acetaminophen and codeine pills) is an opioid, and olanzapine is used for mood and mental health. Taken together, they can add up and make you very drowsy, slow your breathing, and slow down your gut. That slowed gut can cause bad constipation or, rarely, a blockage where the bowel stops moving.
This is mostly a caution based on how these drugs work rather than lots of real-world reports, but it is worth taking seriously. Please don't stop either medicine on your own. Talk with your doctor or pharmacist. Your care team can adjust doses and watch you closely so you stay safe.
Effect: Additive CNS and respiratory depression plus additive reduction in gastric motility, raising the risk of oversedation, respiratory depression, severe constipation, urinary retention, and paralytic ileus.
Mechanism: Codeine (an opioid; note it is a prodrug bioactivated by CYP2D6 to morphine) and olanzapine both cause CNS depression; olanzapine also has anticholinergic activity that compounds opioid-induced GI hypomotility.
- Direction: Additive PD effect, not PK.
- Evidence: Theoretical; severity major; onset unspecified.
- Management: Reserve for when alternatives are inadequate; use lowest effective codeine or CNS-depressant dose for shortest duration. Monitor sedation, respiratory rate, bowel function, and urinary retention. Consider prescribing naloxone.
What happens
Increased risk of paralytic ileus and an increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough medication products with CNS depressants2. Restrict the joint use of codeine and CNS depressants to patients in whom other options prove insufficient. When such combined use cannot be avoided, apply the smallest dose and the briefest duration needed to reach therapeutic objectives. Furthermore, giving codeine together with anticholinergics can heighten 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, along with careful 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 should be considered 134.
Why it happens (mechanism)
Additive effects on gastric motility; additive CNS depression
How to manage this interaction
If your care team decides you need both, here is what typically helps:
- Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may use the lowest effective dose of the codeine or the olanzapine for the shortest time needed, and may monitor you more closely.
- Watch for warning signs: heavy drowsiness, slow or shallow breathing, trouble urinating, and severe constipation or a bloated, painful belly.
- Your prescriber may also give you naloxone for emergencies, just as a safety net.
Call your pharmacist or prescriber if these effects show up or if you feel unusually sedated.
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 occurring between 2004 and 2011 and involving opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and greater than prescribed doses of both drug classes likewise increased significantly from 0.6 to 1.7 per 100,000, and overdose deaths caused by benzodiazepines increased significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times higher than 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 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 those taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths grew as 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. Because of 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 Acetaminophen And Codeine and Olanzapine together?
Combining codeine with olanzapine can add up to dangerous drowsiness, slowed breathing, and a sluggish or blocked gut, so use both only when needed at the lowest doses and stay in touch with your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Olanzapine 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 Olanzapine interaction managed?
If your care team decides you need both, here is what typically helps: Keep taking both exactly as prescribed unless your doctor or pharmacist tells you otherwise. Your team may use the lowest effective dose of the codeine or the olanzapine for the shortest time needed, and may monitor you more closely. Watch for warning signs: heavy drowsiness, slow or shallow breathing, trouble urinating, and se… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Olanzapine 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 Olanzapine
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