Amphetamine and Acetaminophen And Codeine: 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
Amphetamine
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 medicine) along with an amphetamine (like Dexedrine or Zenzedi). Both of these can raise levels of a brain chemical called serotonin. When two serotonin-raising medicines are combined, there is a small chance of a reaction called serotonin syndrome.
Signs to watch for include feeling agitated or confused, a fast heartbeat, sweating, shivering, muscle twitching, or shaking. This is considered a theoretical risk, meaning it doesn't happen often, but it's worth knowing. The good news is your care team can manage this safely by watching you closely, especially when either dose is being started or changed. If anything feels off, call your pharmacist or doctor.
Effect: Additive serotonergic activity may increase the risk of serotonin syndrome when codeine-containing analgesics are combined with amphetamines (which enhance monoaminergic, including serotonergic, transmission).
- Direction: Additive pharmacodynamic (PD) effect, not a PK/metabolic interaction.
- Severity/Evidence: Rated major but theoretical; onset unspecified.
- Monitoring: Watch for hyperthermia, autonomic instability, neuromuscular signs (clonus, hyperreflexia, tremor, rigidity), and mental status changes, especially at initiation and dose changes.
- Management: If serotonin syndrome is suspected, discontinue codeine and provide supportive care. Doses may be individualized by the care team.
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
If both medicines are prescribed together, this can usually be managed safely.
- Keep taking both as prescribed unless your prescriber tells you otherwise. Do not start, stop, or change either one on your own.
- Your care team may watch you more closely, especially when either medicine is first started or a dose is adjusted.
- Doses may need to be adjusted and individualized by your team.
- Contact your pharmacist or doctor right away if you notice agitation, confusion, fast heartbeat, heavy sweating, shivering, muscle twitching, or tremor.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Amphetamine and Acetaminophen And Codeine together?
Combining acetaminophen/codeine with an amphetamine carries a theoretical risk of serotonin syndrome from additive serotonin effects; keep taking both as prescribed, and report agitation, fast heartbeat, sweating, or muscle twitching to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Amphetamine 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 Amphetamine and Acetaminophen And Codeine interaction managed?
If both medicines are prescribed together, this can usually be managed safely. Keep taking both as prescribed unless your prescriber tells you otherwise. Do not start, stop, or change either one on your own. Your care team may watch you more closely, especially when either medicine is first started or a dose is adjusted. Doses may need to be adjusted and individualized by your team. Contact your p… 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 Amphetamine 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 Amphetamine
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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