Acetaminophen And Codeine and Tizanidine: 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
Tizanidine
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 slow you down. The codeine in your pain pill is an opioid, and tizanidine is a muscle relaxer. Each one can make you sleepy, relax your breathing, and lower your blood pressure. Taken together, those calming effects can add up and become stronger than you would expect from either one alone.
Signs to watch for include very heavy drowsiness, slow or shallow breathing, feeling confused or dizzy, trouble peeing, or serious constipation. Please don't stop either medicine on your own. Your care team can manage this safely by using the lowest dose that works and keeping a closer eye on you. Ask your pharmacist or doctor if you have any concerns.
Additive CNS and respiratory depression. Codeine (opioid agonist, also a CYP2D6 prodrug activated to morphine) combined with tizanidine (central alpha-2 agonist muscle relaxant) produces overlapping pharmacodynamic depression rather than a metabolic interaction.
- Direction: increased sedation, hypotension, respiratory depression, and potential coma/death; also increased urinary retention and reduced GI motility (risk of paralytic ileus).
- Evidence: theoretical; severity major; onset unspecified.
- Management: reserve for patients without adequate alternatives; use lowest effective dose and shortest duration. Decrease codeine and/or tizanidine dose as needed. Monitor sedation, respiratory rate, blood pressure, urinary retention, and bowel function. Consider prescribing naloxone.
What happens
Increased risk of urinary retention and/or severe constipation leading to paralytic ileus, increased risk of profound sedation, respiratory depression, coma and death
Interaction Deep Dive
Taking dihydrocodeine together with medications that act as skeletal muscle relaxants and CNS depressants can heighten the likelihood of hypotension, respiratory depression, profound sedation, coma, and death. Combined administration of dihydrocodeine with CNS depressants should be limited to patients for whom other options are insufficient. When such concurrent use cannot be avoided, employ the smallest dose and briefest duration required to meet therapeutic objectives. This combination may also raise the risk of urinary retention and/or severe constipation, potentially progressing to paralytic ileus. Watch for indications of urinary retention, decreased gastric motility, respiratory depression, and sedation. Because respiratory depression may exceed what would otherwise be anticipated when a muscle relaxant is added, reduce the dose of dihydrocodeine and/or the muscle relaxant as needed. Advise patients and caregivers about this possible interaction and teach them to recognize the signs and symptoms of respiratory depression (including sedation). Should concurrent use be 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
This combination can be used, but it needs care. Keep taking both exactly as prescribed unless your doctor tells you otherwise.
- Your care team will usually reserve this combination for when other options aren't enough, and use the lowest dose for the shortest time needed.
- The dose of the codeine and/or tizanidine may be adjusted and individualized, and your team may monitor you more closely.
- Watch for and report heavy drowsiness, slow or shallow breathing, dizziness, trouble urinating, or severe constipation.
- Ask whether naloxone (a rescue medicine for opioid overdose) is appropriate to have on hand.
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 likelihood of drug-related death compared with taking opioid analgesics by themselves. Given the comparable pharmacological characteristics, a similar risk can reasonably be anticipated when other CNS depressant medications are combined with opioid analgesics 12.
Common questions
Can I take Acetaminophen And Codeine and Tizanidine together?
Codeine and tizanidine both depress the nervous system, so combining them can add up to dangerous sedation, slowed breathing, low blood pressure, and constipation or urinary retention. Keep taking both as prescribed, watch for these signs, and let your pharmacist or doctor manage the dose and monitoring. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Tizanidine 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 Tizanidine interaction managed?
This combination can be used, but it needs care. Keep taking both exactly as prescribed unless your doctor tells you otherwise. Your care team will usually reserve this combination for when other options aren't enough, and use the lowest dose for the shortest time needed. The dose of the codeine and/or tizanidine may be adjusted and individualized, and your team may monitor you more closely. Watch… 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 Tizanidine 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 Tizanidine
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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