Acetaminophen And Codeine and Nicomorphine: 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
Nicomorphine
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 and codeine product contains codeine, a pain reliever, and nicomorphine is a strong opioid too. When you take two opioids together, their calming effects add up. That can make you very drowsy and, more importantly, can slow your breathing too much.
There is also a smaller, theoretical concern that opioids can build up too much serotonin in the body, which can cause things like restlessness, shaking, sweating, or a fast heartbeat. The good news is your care team can manage this by keeping doses as low as possible and watching you closely. Call your doctor right away if you feel unusually sleepy, confused, or short of breath.
Effect: Additive CNS and respiratory depression, plus a theoretical risk of serotonin syndrome, when combining two opioids (codeine plus nicomorphine).
- Mechanism: Additive mu-opioid CNS depression; additive serotonergic effects.
- Direction/magnitude: Pharmacodynamic, not PK-mediated. Severity rated major; evidence theoretical.
- Onset: Unspecified; highest risk at initiation and dose escalation.
- Management: Avoid if possible; if needed, use lowest effective dose and shortest duration. Monitor for sedation, respiratory depression, and serotonin syndrome. Consider co-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 cough preparations with CNS depressants2. When codeine products intended for uses other than cough are involved, limit their combination with CNS depressants to patients in whom other options fall short. Should combined therapy be required, apply the smallest dose over the briefest period that meets the treatment objectives. It may be appropriate to lower the dose of either codeine or the CNS depressant, along with vigilant monitoring for sedation, respiratory depression, and any indications of serotonin syndrome. Furthermore, using opioids together with serotonergic agents has led to serotonin syndrome. If such combined use becomes necessary, observe the patient closely, especially when initiating therapy and modifying doses. Prescribing naloxone for emergency management of opioid overdose should be considered. 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 and do not stop or change either one on your own. Because these are two opioids, care teams usually try to avoid using them together, and if both are truly needed they use the lowest dose for the shortest time.
- Your team may adjust and individualize the doses and monitor you more closely, especially when starting or changing a dose.
- Ask whether a naloxone rescue kit is right for you.
- Get urgent help for slow or shallow breathing, extreme drowsiness, or confusion.
- Report agitation, shivering, sweating, muscle twitching, or a racing heart.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) One study found that emergency department visits related to nonmedical use that occurred between 2004 and 2011 and involved both opioid analgesics and benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributed 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 attributed 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, patients taking opioid analgesics who had a history of a benzodiazepine prescription showed a significant 2.33 fold increase in the risk of fatal overdose, and those with a current benzodiazepine prescription showed a 3.86 fold increase, compared with patients taking opioid analgesics without any 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 together with benzodiazepines raises the risk of drug-related mortality relative to 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 during concurrent use of opioids with serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Nicomorphine together?
Combining codeine with nicomorphine stacks two opioids, raising the risk of dangerous drowsiness and slowed breathing, so use together should be avoided when possible and closely monitored when necessary. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Nicomorphine 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 Nicomorphine interaction managed?
Keep taking both exactly as prescribed and do not stop or change either one on your own. Because these are two opioids, care teams usually try to avoid using them together, and if both are truly needed they use the lowest dose for the shortest time. Your team may adjust and individualize the doses and monitor you more closely, especially when starting or changing a dose. Ask whether a naloxone res… 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 Nicomorphine 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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