Acetaminophen And Codeine and Papaveretum: 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
Papaveretum
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 Tylenol with codeine contains codeine, and papaveretum is a mix of opioids too. When you take two opioids together, their effects add up. That can make you very drowsy, slow your breathing, and, more rarely, cause a reaction called serotonin syndrome (which can bring agitation, shakiness, sweating, or a fast heartbeat).
The good news is your care team can manage this safely. They may use the lowest dose for the shortest time and watch you closely. Please don't stop or change either medicine on your own. Just check in with your pharmacist or doctor, and get help right away if breathing becomes slow or you feel very sleepy or confused.
Additive risk: Both agents are opioids, so combining them produces additive CNS and respiratory depression plus additive serotonergic effects, raising the risk of serotonin syndrome. This is a pharmacodynamic interaction, not a metabolic one.
- Direction: increased opioid effect and toxicity risk
- Severity: major; evidence: theoretical
- Onset: unspecified; heightened during initiation and dose changes
Management: Avoid where possible. If needed, use the lowest effective dose and shortest duration. Consider reducing the dose of one agent. Monitor for sedation, respiratory depression, and serotonin syndrome. 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 cough medication formulations with CNS depressants2. When it comes to codeine products that are not intended for cough, restrict their concurrent use with CNS depressants to those patients for whom other options are insufficient. Should combined use be required, employ the smallest dose over the briefest period needed to meet treatment objectives. It is worth considering a reduced dose of either codeine or the CNS depressant, along with vigilant monitoring for sedation, respiratory depression, and the signs and symptoms of serotonin syndrome. Serotonin syndrome has also occurred when opioids are used together with serotonergic drugs. If such combined use is required, observe the patient closely, especially when starting therapy and when doses are being adjusted. Naloxone may be considered for prescribing to provide emergency management of opioid overdose. If serotonin syndrome is 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 these are two opioids, teams usually take extra care:
- They may avoid using both together, or reserve it for when other options aren't enough.
- Doses may be adjusted and individualized, often using the lowest amount for the shortest time.
- They may monitor you more closely for heavy sedation, slow breathing, or serotonin syndrome, especially when starting or changing doses.
- Your prescriber may provide naloxone as an emergency backup.
Tell your pharmacist or doctor if you feel very drowsy, breathe slowly, or notice agitation, shaking, sweating, 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 between 2004 and 2011 that involved opioid analgesics and 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 caused by benzodiazepines rose 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 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 among patients taking opioid analgesics who had a history of a benzodiazepine prescription and rose by 3.86 fold among 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 the daily dose of benzodiazepines increased 2.
d) Observational studies have shown that combined use of opioid analgesics and benzodiazepines raises the risk of drug-related mortality relative to use of opioid analgesics alone. Given their similar pharmacological properties, it is reasonable to anticipate a comparable 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 with the concurrent use of opioids and serotonergic drugs 34.
Common questions
Can I take Acetaminophen And Codeine and Papaveretum together?
Combining these two opioids adds up their sedating and breathing-slowing effects and can rarely trigger serotonin syndrome, so your team will use the lowest dose for the shortest time and watch you closely. Never stop or change either medicine on your own, and get help fast if breathing slows or you feel very sleepy or confused. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Papaveretum 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 Papaveretum interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because these are two opioids, teams usually take extra care: They may avoid using both together, or reserve it for when other options aren't enough. Doses may be adjusted and individualized, often using the lowest amount for the shortest time. They may monitor you more closely for heavy sedation, slow breathing, or… 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 Papaveretum 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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