Acetaminophen And Codeine and Opium: 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
Opium
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 are opioids. Your acetaminophen with codeine contains codeine, and opium is also a strong opioid. Taking them together stacks two similar drugs on top of each other. That can make you very drowsy, slow your breathing too much, and in rare cases cause a serious reaction called serotonin syndrome (things like agitation, fast heartbeat, sweating, and shaking).
The good news is your care team can manage this. They may use the lowest dose needed for the shortest time and watch you closely. Please don't stop or change anything on your own. Instead, talk with your pharmacist or doctor, and ask if you should have naloxone on hand just in case.
Additive CNS and respiratory depression plus additive serotonergic risk from combining two opioids (codeine-containing product and opium).
- Mechanism: pharmacodynamic additive opioid CNS/respiratory depression; additive serotonergic effect (opioids can precipitate serotonin syndrome).
- Direction: increased opioid effect and toxicity risk.
- Evidence: theoretical; severity major; onset unspecified.
- Management: avoid where possible; if needed use lowest dose/shortest duration, reduce dose of codeine or the other agent, monitor for sedation, respiratory depression, and serotonin syndrome, especially at initiation/titration. Consider prescribing naloxone. Discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Do not combine opioid-containing cough preparations with CNS depressants2. When it comes to codeine products intended for uses other than cough, limit their combined use with CNS depressants to those patients in whom other options prove insufficient. Should concurrent administration be required, apply the smallest dose and briefest duration needed to meet therapeutic aims. Reducing the dose of either codeine or the CNS depressant is worth considering, along with vigilant monitoring for sedation, respiratory depression, and manifestations of serotonin syndrome. Serotonin syndrome has also occurred when opioids are taken together with serotonergic agents. If joint use is unavoidable, monitor the patient closely, especially when therapy begins and when doses are being modified. Prescribing naloxone for emergency management of opioid overdose is worth considering. Should serotonin syndrome be suspected, stop codeine 134.
Why it happens (mechanism)
Additive CNS depression; additive serotonergic effects
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because both are opioids, your team will try to avoid using them together, and if both are truly needed, they will use the lowest dose for the shortest time and monitor you closely.
- Watch for heavy drowsiness, slow or shallow breathing, confusion, agitation, fast heartbeat, sweating, or shaking.
- Ask your pharmacist or doctor whether you should have naloxone at home.
- Call your care team right away if you notice worrying symptoms, especially when starting or changing doses.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that between 2004 and 2011, the rate of emergency department visits related to nonmedical use involving both opioid analgesics and benzodiazepines rose significantly, from 11 to 34.2 per 100,000. Deaths from drug overdose attributable to prescribed and higher than prescribed doses of both drug classes likewise increased significantly, from 0.6 to 1.7 per 100,000, and overdose deaths attributable to benzodiazepines increased significantly from 18% to 31% 2.
b) In a prospective cohort study, the rate of overdose deaths associated with dispensing of both opioid analgesics and benzodiazepines was 10 times greater than 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 grew as daily benzodiazepine doses increased 2.
d) Observational studies have shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death compared with using opioid analgesics alone. Given comparable pharmacological properties, it is reasonable to anticipate a similar risk when other CNS depressant drugs are used together with opioid analgesics 34.
e) Instances of serotonin syndrome, a condition that can be life-threatening, have been reported when opioids are used together with serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Opium together?
Combining acetaminophen/codeine with opium stacks two opioids, raising the risk of dangerous sedation, slowed breathing, and serotonin syndrome. Use only if truly needed, at the lowest dose, and ask your care team about closer monitoring and naloxone. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Opium 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 Opium interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because both are opioids, your team will try to avoid using them together, and if both are truly needed, they will use the lowest dose for the shortest time and monitor you closely. Watch for heavy drowsiness, slow or shallow breathing, confusion, agitation, fast heartbeat, sweating, or shaking. Ask your pharmacist o… 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 Opium 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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