Acetaminophen And Codeine and Metoclopramide: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Metoclopramide
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 can make you sleepy. The codeine in your pain medicine is an opioid, and it can slow down your brain and breathing. Metoclopramide, used for nausea or stomach problems, can also cause drowsiness. When you take them together, those calming effects can add up, so you may feel more tired, dizzy, or foggy than usual.
This is mostly a caution based on how the drugs work rather than lots of case reports, but it's worth taking seriously. Please don't stop either medicine on your own. Talk with your pharmacist or doctor. Your care team can manage this by adjusting doses and keeping a closer eye on you.
Effect: Additive CNS depression when metoclopramide is combined with the codeine (opioid) component of acetaminophen/codeine. Codeine is a prodrug activated by CYP2D6 to morphine, but this is a pharmacodynamic interaction, not metabolic, so prodrug status does not change the direction here.
- Mechanism: Additive sedative/CNS-depressant effects.
- Direction: Increased sedation, respiratory depression risk, psychomotor impairment.
- Onset: Unspecified; evidence is theoretical.
- Severity: Major; combination generally best avoided.
- Management: If coadministration is necessary, use lowest effective doses, monitor sedation and respiratory status, counsel on driving/operating machinery.
What happens
Increased risk of CNS depression
Interaction Deep Dive
Using metoclopramide together with a CNS depressant (such as sedatives, hypnotics, opiates, and anxiolytics) can heighten the likelihood of CNS depression, so this combination should be avoided. When coadministration cannot be avoided, watch for adverse effects1.
Why it happens (mechanism)
Additive pharmacologic effect
How to manage this interaction
Keep taking both exactly as prescribed unless your care team tells you otherwise. When these are used together, the main plan is to watch for added drowsiness.
- Your care team may avoid the combination or use the lowest effective doses and monitor you more closely.
- Watch for excess sleepiness, dizziness, confusion, or slowed breathing.
- Avoid alcohol and other sedating medicines unless cleared by your team.
- Be careful driving or operating machinery until you know how you feel.
Tell your pharmacist or prescriber about any strong drowsiness so your doses can be adjusted and individualized.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Metoclopramide together?
Taking metoclopramide with acetaminophen/codeine can add up their sedating effects, so watch for extra drowsiness or slowed breathing and check with your pharmacist or doctor about the safest way to use them together. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Metoclopramide 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 Metoclopramide interaction managed?
Keep taking both exactly as prescribed unless your care team tells you otherwise. When these are used together, the main plan is to watch for added drowsiness. Your care team may avoid the combination or use the lowest effective doses and monitor you more closely. Watch for excess sleepiness, dizziness, confusion, or slowed breathing. Avoid alcohol and other sedating medicines unless cleared by yo… 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Metoclopramide 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 (1)
- Product Information: REGLAN(R) oral tablets, metoclopramide oral tablets. ANI Pharmaceuticals, Inc. (per FDA), Baudette, MN, 2017. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Metoclopramide
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