Acetaminophen And Codeine and Granisetron: 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
Granisetron
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.
You've been given codeine (combined with acetaminophen for pain) and granisetron, a medicine that helps with nausea. Both can nudge up a brain chemical called serotonin. In rare cases, having too much serotonin at once can cause a reaction called serotonin syndrome, with symptoms like agitation, a fast heartbeat, sweating, shivering, muscle twitching, or feeling confused.
The good news is that this is considered a theoretical risk, meaning it doesn't happen often. Your care team can manage it by keeping an eye on how you feel, especially when you first start or change doses. Please keep taking both as prescribed, and let your doctor or pharmacist know right away if you notice those symptoms.
Effect: Additive serotonergic activity may increase the risk of serotonin syndrome when codeine (with acetaminophen) is combined with granisetron, a 5-HT3 antagonist.
- Mechanism: Additive serotonergic effects (PD interaction), not a metabolic/PK interaction.
- Direction/magnitude: Increased serotonergic burden; magnitude undefined.
- Onset: Unspecified; risk is greatest at initiation and dose escalation.
- Evidence: Theoretical; rated major on severity.
Management: If co-administration is needed, monitor for neuromuscular (clonus, hyperreflexia, rigidity), autonomic (tachycardia, hyperthermia, diaphoresis), and mental status changes. Discontinue codeine and treat supportively if serotonin syndrome is suspected.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Concomitant use of opioids, such as codeine, with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Discontinue codeine if serotonin syndrome is suspected123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. This is a precaution, not a reason to stop on your own.
- Your team may watch you more closely, especially when you first start these or when a dose is changed.
- Learn the warning signs: agitation, confusion, fast heartbeat, high fever, heavy sweating, shivering, muscle twitching or stiffness.
- If these occur, seek medical care promptly, as the codeine may need to be stopped by your prescriber.
Ask your pharmacist or doctor if you have questions about any other serotonergic medicines you take.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Acetaminophen And Codeine and Granisetron together?
Combining codeine (with acetaminophen) and granisetron can slightly raise the risk of serotonin syndrome, so watch for symptoms like agitation, fast heartbeat, sweating, or muscle twitching and report them right away. Keep taking both as prescribed and let your care team monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Granisetron 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 Granisetron interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. This is a precaution, not a reason to stop on your own. Your team may watch you more closely, especially when you first start these or when a dose is changed. Learn the warning signs: agitation, confusion, fast heartbeat, high fever, heavy sweating, shivering, muscle twitching or stiffness. If these occur, seek med… 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 Granisetron 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 (3)
- Product Information: Codeine sulfate oral tablets, codeine sulfate oral tablets. West-Ward Pharmaceuticals Corp (per DailyMed), Eatontown, NJ, 2016. DailyMed
- 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 Granisetron
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