Acetaminophen And Codeine and Mesoridazine: 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
Mesoridazine
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.
Your pain medicine contains codeine, which is an opioid, and it's combined with acetaminophen (Tylenol). Mesoridazine is a medicine that can also make you drowsy and calm your nervous system. When you take both together, those sleepy, slowing effects can stack on top of each other.
The main worry is that this combination can slow your breathing too much, drop your blood pressure, or make you very sedated. In serious cases that can be dangerous. The good news is that your care team can manage this by using the lowest helpful dose for the shortest time and watching you closely. Please don't stop or change either medicine on your own talk with your pharmacist or doctor first.
Effect: Additive CNS and respiratory depression from combining codeine (opioid analgesic) with mesoridazine (phenothiazine, sedating with hypotensive potential).
- Mechanism: Pharmacodynamic additive CNS depression; risk of hypotension, respiratory depression, profound sedation, coma, and death.
- Direction: Increased combined depressant effect (not a metabolic interaction).
- Evidence/onset: Theoretical; onset unspecified. Severity major.
- Management: Reserve co-prescribing for when alternatives are inadequate. Use lowest effective dose and shortest duration; consider lowering the dose of codeine or mesoridazine. Monitor closely for sedation and respiratory depression. Consider prescribing naloxone.
What happens
An increased risk of respiratory and CNS depression
Interaction Deep Dive
Do not combine opioid cough preparations with CNS depressants. Taking opioid analgesics together with benzodiazepines has been linked to higher rates of both emergency department presentations and fatal overdose2. When codeine is used alongside CNS depressants, there is a greater likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Prescribing these agents together should be limited to patients in whom other treatment options are insufficient. Keep both the doses and the length of therapy to the lowest amount necessary. Monitor patients carefully for indications of sedation and respiratory depression. Should combined use be justified, consider providing naloxone for emergency management of opioid overdose341.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both exactly as prescribed and do not stop either on your own. This combination is generally avoided unless your care team decides you need both.
- Your team may use the lowest dose for the shortest time and may lower the dose of one medicine.
- They will watch you closely for heavy sedation, slowed breathing, or low blood pressure.
- Your doctor may also prescribe naloxone as an emergency backup.
Call your pharmacist or prescriber right away if you feel unusually drowsy, confused, dizzy, or short of breath. Ask them before adding any other sedating medicine or alcohol.
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 linked to nonmedical use that occurred between 2004 and 2011 and involved opioid analgesics together with benzodiazepines rose significantly from 11 to 34.2 per 100,000. Drug overdose deaths attributable to prescribed and to greater than 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 associated with the dispensing of both opioid analgesics and benzodiazepines was 10 times greater than that associated 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 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 without any history of a benzodiazepine prescription. The risk of drug overdose deaths increased 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 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 concomitantly with opioid analgesics 34.
Common questions
Can I take Acetaminophen And Codeine and Mesoridazine together?
Codeine plus mesoridazine can stack up sleepy, blood-pressure-lowering, and breathing-slowing effects, which can be dangerous. This combo is usually avoided, but if both are needed your care team will use the lowest dose, monitor you closely, and may prescribe naloxone. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Mesoridazine 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 Mesoridazine interaction managed?
Keep taking both exactly as prescribed and do not stop either on your own. This combination is generally avoided unless your care team decides you need both. Your team may use the lowest dose for the shortest time and may lower the dose of one medicine. They will watch you closely for heavy sedation, slowed breathing, or low blood pressure. Your doctor may also prescribe naloxone as an emergency b… 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 Mesoridazine 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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