Acetaminophen And Codeine and Rizatriptan: 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
Rizatriptan
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, and rizatriptan is a migraine medicine. Both can gently raise a brain chemical called serotonin. When you take them together, there's a small chance that serotonin can climb too high, causing something called serotonin syndrome.
Warning signs include feeling agitated or restless, a fast heartbeat, sweating, shivering, muscle twitching, or shaking. This is uncommon, and the concern here is mostly based on theory rather than lots of real cases. Many people use both safely. The good news is your care team can manage this by watching how you feel, especially when you first start or change a dose. If you notice these symptoms, call your doctor or pharmacist.
Effect: Additive serotonergic activity from codeine (a weak serotonin reuptake inhibitor) plus rizatriptan (a 5-HT1B/1D agonist) may increase the risk of serotonin syndrome.
- Direction: Additive PD effect, not a PK/metabolic interaction; both agents contribute serotonergic tone.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified; highest vigilance at initiation and dose changes.
- Management: Use together only if needed, monitor for hyperthermia, autonomic instability, neuromuscular findings (clonus, hyperreflexia), and altered mental status. Discontinue codeine if serotonin syndrome is suspected and treat supportively.
Acetaminophen is not serotonergic and does not contribute.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Taking opioids like codeine together with serotonergic agents has led to cases of serotonin syndrome. When such combined therapy cannot be avoided, monitor the patient closely, especially when starting treatment and when doses are being adjusted. Should serotonin syndrome be suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
You can usually take both as prescribed, but your care team may watch you a bit more closely, especially when starting either drug or changing a dose.
- Keep taking both unless your doctor or pharmacist tells you otherwise.
- Know the warning signs: restlessness, fast heartbeat, sweating, shivering, muscle twitching or stiffness, or confusion.
- Act on symptoms: contact your prescriber or pharmacist promptly if these appear. If symptoms are severe, seek urgent care.
- Tell your team about any other serotonin-raising medicines, including antidepressants, so your regimen can be tailored to you.
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 Rizatriptan together?
Taking codeine (in your acetaminophen-codeine product) with rizatriptan carries a small, mostly theoretical risk of serotonin syndrome. Keep taking both as prescribed, but watch for restlessness, fast heartbeat, sweating, or muscle twitching, and contact your care team if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Rizatriptan 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 Rizatriptan interaction managed?
You can usually take both as prescribed, but your care team may watch you a bit more closely, especially when starting either drug or changing a dose. Keep taking both unless your doctor or pharmacist tells you otherwise. Know the warning signs: restlessness, fast heartbeat, sweating, shivering, muscle twitching or stiffness, or confusion. Act on symptoms: contact your prescriber or pharmacist pro… 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 Rizatriptan 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 Rizatriptan
These medications also interact with supplements
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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