Dextroamphetamine and Acetaminophen And Codeine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Dextroamphetamine
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 acetaminophen with codeine (a pain reliever) along with dextroamphetamine (a stimulant used for conditions like ADHD). Both can raise levels of a brain chemical called serotonin. When two medicines do this together, there's a small chance of a reaction called serotonin syndrome.
Warning signs can include feeling agitated or restless, a fast heartbeat, sweating, shivering, muscle twitching or stiffness, and confusion. This is considered a possible (theoretical) risk, not something that happens to everyone. The good news is your care team can manage this safely by watching you, especially when you first start or change a dose. If you notice those symptoms, contact your doctor or pharmacist right away.
Effect: Additive serotonergic activity may increase the risk of serotonin syndrome when codeine (an opioid with weak serotonergic properties) is combined with dextroamphetamine (which enhances monoaminergic, including serotonergic, transmission).
- Direction/mechanism: Pharmacodynamic additive serotonergic effect, not a PK interaction. Acetaminophen is not implicated.
- Severity: Major; evidence: theoretical; onset: unspecified.
- Monitoring: Observe for agitation, autonomic instability (tachycardia, hyperthermia, diaphoresis), neuromuscular signs (clonus, hyperreflexia, rigidity), and mental status changes, particularly at initiation and dose changes.
- Management: If serotonin syndrome is suspected, discontinue codeine and provide supportive care.
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
You can usually take both medicines when your care team has decided you need them. Here's how this is typically handled:
- Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise.
- Your team may monitor you more closely, especially when starting either drug or changing a dose.
- Watch for symptoms like agitation, racing heart, sweating, shivering, muscle twitching or stiffness, or confusion.
If any of these happen, contact your prescriber or pharmacist promptly, since codeine may need to be stopped if serotonin syndrome is suspected. Bring up any other serotonergic medicines or supplements you take so your team has the full picture.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Dextroamphetamine and Acetaminophen And Codeine together?
Combining codeine with dextroamphetamine carries a theoretical risk of serotonin syndrome, so watch for symptoms like agitation, rapid heartbeat, sweating, or muscle twitching, especially when starting or adjusting doses, and report them to your care team right away. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Dextroamphetamine and Acetaminophen And Codeine 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 Dextroamphetamine and Acetaminophen And Codeine interaction managed?
You can usually take both medicines when your care team has decided you need them. Here's how this is typically handled: Keep taking both as prescribed unless your doctor or pharmacist tells you otherwise. Your team may monitor you more closely, especially when starting either drug or changing a dose. Watch for symptoms like agitation, racing heart, sweating, shivering, muscle twitching or stiffne… 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 Dextroamphetamine or Acetaminophen And Codeine 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 Dextroamphetamine
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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