Acetaminophen And Codeine and Naratriptan: 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
Naratriptan
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 prescribed two medicines that can both nudge up a brain chemical called serotonin. One is the codeine in your pain pill, and the other is naratriptan, a migraine medicine. When serotonin gets too high, it can cause something called serotonin syndrome. Watch for things like feeling agitated or restless, a fast heartbeat, sweating, shaking, muscle twitching, or a fever.
The good news: this is considered a possible risk rather than something that's proven to happen often. Keep taking both as prescribed, and if you notice those symptoms, especially soon after starting or after a dose change, reach out to your doctor or pharmacist right away. Your care team can manage this.
Effect: Additive serotonergic activity from codeine (an opioid with weak serotonergic properties) and naratriptan (a 5-HT1 agonist) may increase the risk of serotonin syndrome.
- Mechanism: Pharmacodynamic, additive serotonergic effects.
- Direction: Increased serotonergic burden (increased drug effect).
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified; risk highest at initiation and dose titration.
- Monitoring: Observe for agitation, autonomic instability (tachycardia, hyperthermia, diaphoresis), neuromuscular signs (clonus, hyperreflexia, tremor).
Management: If concomitant use is needed, observe closely, particularly during initiation and adjustments. 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. When such combined therapy is required, the patient should be monitored closely, especially at the start of treatment and whenever doses are changed. If serotonin syndrome is suspected, codeine should be stopped123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This combination can be used together when your care team decides it's appropriate, so keep taking both exactly as prescribed unless told otherwise.
- Watch closely during the first days and after any dose change, since that's when the risk is highest.
- Know the warning signs: restlessness or agitation, fast heartbeat, high temperature, sweating, shivering, muscle twitching or stiffness, and confusion.
- Act early: if these appear, contact your prescriber or pharmacist promptly. Your doctor may stop the codeine if serotonin syndrome is suspected.
Ask your pharmacist if you're unsure how to spot the symptoms.
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 Naratriptan together?
Taking codeine with naratriptan may slightly raise the risk of serotonin syndrome, so keep taking both as prescribed but watch for symptoms like agitation, fast heartbeat, sweating, and muscle twitching, and call your care team right away if they appear. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Naratriptan 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 Naratriptan interaction managed?
This combination can be used together when your care team decides it's appropriate, so keep taking both exactly as prescribed unless told otherwise. Watch closely during the first days and after any dose change, since that's when the risk is highest. Know the warning signs: restlessness or agitation, fast heartbeat, high temperature, sweating, shivering, muscle twitching or stiffness, and confusio… 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 Naratriptan 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 Naratriptan
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