Carbinoxamine 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
Carbinoxamine
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 carbinoxamine is an older antihistamine. Both can make you sleepy and slow your breathing, so taking them together can add up and leave you very drowsy or breathing too slowly. Codeine also slows the gut and carbinoxamine has a drying effect, so together they can cause bad constipation or trouble emptying your bladder. In rare cases, the gut can nearly stop moving.
The good news is your care team can manage this. They may use the lowest dose for the shortest time and watch you closely. Let them know if you feel very sleepy, short of breath, or constipated.
Additive CNS/respiratory depression and additive anticholinergic/antimotility effects. Codeine (a mu-opioid agonist and CYP2D6 prodrug converted to morphine) combined with carbinoxamine (a sedating, anticholinergic first-generation antihistamine) can produce additive sedation and respiratory depression, plus reduced GI motility and urinary retention, potentially leading to paralytic ileus.
- Direction: additive PD interaction, increased combined effect.
- Evidence: theoretical; severity rated major.
- Onset: unspecified.
- Management: avoid if possible; if necessary use lowest dose/shortest duration, consider dose reduction of codeine or the CNS depressant, monitor for sedation, respiratory depression, urinary retention, and reduced gastric motility. 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
Keep taking both exactly as prescribed and do not stop either one on your own. Your care team decides whether this combination is truly needed and, if so, typically uses the lowest dose for the shortest time.
- Your team may lower the dose of the codeine or the antihistamine and monitor you more closely for drowsiness, slow breathing, constipation, or trouble urinating.
- They may consider prescribing naloxone as an emergency safeguard.
- Tell your pharmacist or prescriber right away about heavy sedation, breathing that feels slow or shallow, or not being able to pass urine or stool.
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 that involved opioid analgesics along 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 with the 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 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 without a 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 together with benzodiazepines raises the risk of drug-related mortality 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 concurrently with opioid analgesics 34.
Common questions
Can I take Carbinoxamine and Acetaminophen And Codeine together?
Combining codeine with the sedating antihistamine carbinoxamine can add up to dangerous drowsiness, slowed breathing, and severe constipation, so use it only if your care team says it is needed and watch closely for these signs. Talk with your pharmacist or doctor before combining them. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Carbinoxamine 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 Carbinoxamine and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed and do not stop either one on your own. Your care team decides whether this combination is truly needed and, if so, typically uses the lowest dose for the shortest time. Your team may lower the dose of the codeine or the antihistamine and monitor you more closely for drowsiness, slow breathing, constipation, or trouble urinating. They may consider prescribing… 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 Carbinoxamine 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
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