Meperidine 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
Meperidine
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 are opioid pain medicines. Your Tylenol with codeine already has codeine in it, and meperidine (Demerol) is a second opioid. Taking them together adds up. That can make you very sleepy or slow your breathing more than either one alone.
There is also a rare risk of something called serotonin syndrome, which can cause agitation, a fast heartbeat, shaking, or fever. This warning is mostly a precaution based on how these drugs work, not from lots of case reports. Please don't stop either medicine on your own. Talk with your pharmacist or doctor so they can pick the safest plan and doses for you.
Additive CNS and respiratory depression, plus additive serotonergic risk, when combining acetaminophen/codeine with meperidine (both opioids).
- Mechanism: additive CNS/respiratory depression; both agents have serotonergic activity, raising serotonin syndrome risk.
- Direction: increased opioid effect (both are active opioid analgesics here; codeine is a CYP2D6-activated prodrug but that is not the driver of this additive interaction).
- Evidence: theoretical; severity rated major.
- Management: avoid where possible; if needed, use lowest effective dose and shortest duration. Monitor for sedation, hypoventilation, and serotonin syndrome (autonomic instability, clonus, hyperreflexia). Consider naloxone. Discontinue if serotonin syndrome suspected.
What happens
Increased risk of respiratory and CNS depression and an increased risk of serotonin syndrome
Interaction Deep Dive
Do not combine opioid-based cough preparations with CNS depressants2. In the case of codeine products that are not intended for cough, limit combined use with CNS depressants to those patients for whom other options prove inadequate. When such concurrent use cannot be avoided, apply the lowest possible dose over the briefest period required to meet the therapeutic objectives. A reduced dose of either codeine or the CNS depressant should be considered, along with vigilant monitoring for sedation, respiratory depression, and any indications of serotonin syndrome. Serotonin syndrome has also been reported when opioids are taken alongside serotonergic agents. Should combined use be required, watch the patient closely, especially when starting therapy and when adjusting the dose. Prescribing naloxone for emergency management of opioid overdose is worth considering. Codeine should be stopped if serotonin syndrome is suspected 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 try to avoid using them together, or use the lowest dose for the shortest time when both are truly needed.
- Your doses may be adjusted and individualized by your care team, and they may monitor you more closely, especially when starting or changing doses.
- Watch for heavy drowsiness, slow or shallow breathing, confusion, or serotonin symptoms (agitation, shaking, racing heart, fever).
- Your prescriber may offer naloxone as a safety measure.
- Call your pharmacist or doctor with questions, and seek urgent help for breathing trouble.
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. Deaths from drug overdose attributable to prescribed doses and doses exceeding those prescribed for 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 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 those taking opioid analgesics who had no history of a benzodiazepine prescription. The risk of death from drug overdose 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 mortality relative to using opioid analgesics alone. Given the 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 the concurrent use of opioids with serotonergic drugs 34.
Common questions
Can I take Meperidine and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with meperidine stacks two opioids, raising the risk of over-sedation, slowed breathing, and rarely serotonin syndrome; use together only when necessary and let your care team set the doses and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Meperidine 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 Meperidine and Acetaminophen And Codeine interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. Because these are two opioids, teams usually try to avoid using them together, or use the lowest dose for the shortest time when both are truly needed. Your doses may be adjusted and individualized by your care team, and they may monitor you more closely, especially when starting or changing doses. Watch for heavy dr… 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 Meperidine 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
Keep reading about Acetaminophen And Codeine
Keep reading about Meperidine
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