Acetaminophen And Codeine and Loxapine: 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
Loxapine
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.
Taking these together can add up in ways to watch out for. Your acetaminophen with codeine is an opioid pain reliever, and loxapine (Adasuve) is a medicine that calms the mind. Both can make you sleepy and slow your breathing, so combining them can make those effects stronger. They can also both slow down your gut and bladder, which can lead to bad constipation or trouble passing urine.
This concern is based mostly on how these drugs work, not on lots of real cases. The good news is your care team can manage it by using the lowest helpful dose and keeping an eye on you. Never stop or change either one on your own. Just talk with your pharmacist or doctor.
Additive CNS and PD interaction. Codeine (an opioid; a prodrug activated via CYP2D6 to morphine) plus loxapine produces additive CNS and respiratory depression and additive reduction in GI/GU motility.
- Direction: increased opioid/sedative effect and anticholinergic-type slowing (constipation, urinary retention, risk of paralytic ileus).
- Mechanism: additive CNS depression; additive effects on gastric motility.
- Evidence: theoretical; severity rated major.
- Management: avoid where possible; if needed, use lowest effective dose and shortest duration, consider reducing codeine or loxapine dose, monitor sedation, respiratory rate, gastric motility, 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-based cough preparations with CNS depressants2. The joint use of codeine alongside CNS depressants should be limited to those patients in whom other options prove insufficient. When such combined use cannot be avoided, employ the smallest dose over the briefest period required to meet therapeutic objectives. Furthermore, giving codeine together with anticholinergics can raise the likelihood of urinary retention and/or severe constipation, potentially progressing to paralytic ileus. Reducing the dose of either codeine or the CNS depressant should be considered, along with vigilant observation for urinary retention, decreased gastric motility, sedation, and respiratory depression. Should concurrent administration 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
Your care team can handle this by tailoring and watching. This combination is usually avoided when possible, but when both are truly needed it can be used carefully.
- Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your team may use the lowest dose and shortest course, and may adjust the dose of the codeine or the loxapine, individualized to you.
- They may monitor you more closely for drowsiness, slowed breathing, severe constipation, and trouble urinating.
- Your prescriber may also offer naloxone as a safety measure.
Call your pharmacist or doctor if you feel very sleepy, breathe slowly, or cannot pass stool or urine.
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 took place 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 higher than 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 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 taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of drug overdose deaths increased 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 death compared with using opioid analgesics alone. Given the comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Loxapine together?
Combining acetaminophen with codeine and loxapine can add up to more sedation, slowed breathing, and gut or bladder slowing, so it is best avoided when possible. If both are needed, your care team will use the lowest dose and monitor you closely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Loxapine 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 Loxapine interaction managed?
Your care team can handle this by tailoring and watching. This combination is usually avoided when possible, but when both are truly needed it can be used carefully. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your team may use the lowest dose and shortest course, and may adjust the dose of the codeine or the loxapine, individualized to you. They may monitor you… 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 Loxapine 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 Loxapine
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