Acetaminophen And Codeine and Sumatriptan: 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
Sumatriptan
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 prescribed two medicines that can each nudge up a brain chemical called serotonin. One is the codeine in your acetaminophen-codeine pills, and the other is sumatriptan, a migraine medicine. When two serotonin-raising drugs are used together, there's a small chance of a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or restless, a fast heartbeat, sweating, shivering, muscle twitching, or shakiness. This is considered a theoretical risk, meaning it's not common, but it's worth knowing. The good news: your care team can manage this by watching you closely, especially when you first start or change a dose. If you notice those symptoms, reach out to your pharmacist or doctor.
Effect: Additive serotonergic activity, giving a theoretical increased risk of serotonin syndrome when codeine (in acetaminophen/codeine) is combined with sumatriptan, a 5-HT1B/1D agonist.
Direction/mechanism: Pharmacodynamic (additive), not a PK/enzyme interaction. Both agents contribute serotonergic tone.
- Severity: Major, but evidence is theoretical.
- Onset: Unspecified; highest vigilance at initiation and dose changes.
- Monitor: Autonomic instability, neuromuscular signs (clonus, hyperreflexia, tremor, rigidity), agitation, hyperthermia.
- Management: If concomitant use is needed, observe closely; discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Serotonin syndrome has been reported when opioids like codeine are taken together with serotonergic agents. Should combined therapy be required, monitor the patient closely, especially when starting treatment and when doses are being modified. If serotonin syndrome is suspected, stop codeine123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
In most cases these two can be used together safely, and you should keep taking both as prescribed unless your prescriber tells you otherwise.
Here's how a care team typically handles this:
- They watch you more closely, especially when you first start either drug or change a dose.
- They may stop the codeine if serotonin syndrome is suspected.
What you can do: Learn the warning signs (agitation, fast heartbeat, sweating, shivering, muscle twitching or stiffness, fever) and contact your pharmacist or doctor right away if they appear. Let your team know all the medicines you take so they can tailor and monitor your therapy.
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 Sumatriptan together?
Using codeine (in acetaminophen-codeine) with sumatriptan carries a small, theoretical risk of serotonin syndrome from additive serotonin effects; keep taking both as prescribed but watch for symptoms like agitation, rapid heartbeat, sweating, or muscle twitching and call your pharmacist or doctor if they occur. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Sumatriptan 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 Sumatriptan interaction managed?
In most cases these two can be used together safely, and you should keep taking both as prescribed unless your prescriber tells you otherwise. Here's how a care team typically handles this: They watch you more closely, especially when you first start either drug or change a dose. They may stop the codeine if serotonin syndrome is suspected. What you can do: Learn the warning signs (agitation, fast… 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 Sumatriptan 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 Sumatriptan
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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