Acetaminophen And Codeine and Methocarbamol: 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
Methocarbamol
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, an opioid, along with acetaminophen (Tylenol). Methocarbamol (Robaxin) is a muscle relaxant. Both of these can slow down your brain and body. When you take them together, that calming effect can add up. This may make you feel very drowsy or dizzy, and in more serious cases it can slow your breathing.
The good news is that this can be managed. Your care team may use the lowest dose that works, watch you more closely, and tell you the warning signs to look for, like heavy sleepiness or slow, shallow breathing. Please don't stop or change either medicine on your own. Talk with your pharmacist or doctor about using them safely.
Additive CNS depression between codeine (opioid) and methocarbamol (centrally acting skeletal muscle relaxant), with possible enhanced neuromuscular effects. Both are pharmacodynamic CNS depressants, so combined use raises the risk of profound sedation, hypotension, respiratory depression, and rarely coma or death.
- Direction: additive/synergistic PD interaction (not PK). Neither drug is a prodrug issue relevant here; codeine's opioid effect is unchanged in mechanism.
- Severity/Evidence: major; theoretical, class-based.
- Management: reserve concurrent use for when alternatives are inadequate; use lowest effective dose and shortest duration; reduce codeine and/or methocarbamol dose; monitor for sedation and respiratory depression; consider prescribing naloxone.
What happens
Increased risk of profound sedation, respiratory depression, coma and death
Interaction Deep Dive
Taking codeine together with skeletal muscle relaxants and CNS depressants can heighten the likelihood of profound sedation, respiratory depression, hypotension, coma, and death. Combined use of codeine and CNS depressants should be limited to patients for whom other options are insufficient. When such combined use cannot be avoided, employ the lowest effective dose and the shortest duration required to meet therapeutic objectives. A reduced dose of either codeine or the CNS depressant should be considered, along with close observation for sedation and respiratory depression. Patients and caregivers should be advised of this possible interaction and taught to recognize the signs and symptoms of respiratory depression (including sedation). Because respiratory depression may exceed what would otherwise be anticipated when a skeletal muscle relaxant is used concurrently, the dosage of codeine and/or the muscle relaxant should be lowered as needed. When concurrent use is justified, consider prescribing naloxone for the emergency management of opioid overdose12.
Why it happens (mechanism)
Enhanced neuromuscular blockade; additive CNS depression
How to manage this interaction
If your care team has you on both, keep taking them exactly as prescribed unless told otherwise. Here is how this is typically handled:
- Your team may use the lowest effective dose for the shortest time needed, and may lower the dose of the codeine, the methocarbamol, or both.
- They may monitor you more closely for sedation and breathing changes.
- They may discuss having naloxone on hand for emergencies.
Watch for heavy drowsiness, confusion, dizziness, or slow, shallow breathing. Ask your pharmacist or prescriber before adding alcohol or other sedating medicines, and report these symptoms right away.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) Observational research has shown that using opioid analgesics together with benzodiazepines raises the risk of drug-related death when compared with the use of opioid analgesics by themselves. Given their comparable pharmacological characteristics, it is reasonable to anticipate a similar risk when other CNS depressant medications are used concurrently with opioid analgesics 12.
Common questions
Can I take Acetaminophen And Codeine and Methocarbamol together?
Codeine and methocarbamol both depress the central nervous system, so together they can cause excessive sedation and slowed breathing. Use only as prescribed, watch for heavy drowsiness or slow breathing, and ask your care team how to take them safely. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Methocarbamol 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 Methocarbamol interaction managed?
If your care team has you on both, keep taking them exactly as prescribed unless told otherwise. Here is how this is typically handled: Your team may use the lowest effective dose for the shortest time needed, and may lower the dose of the codeine, the methocarbamol, or both. They may monitor you more closely for sedation and breathing changes. They may discuss having naloxone on hand for emergenc… 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 Methocarbamol 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 (2)
- 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 Methocarbamol
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major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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