Cocaine 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
Cocaine
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 medicine Tylenol with Codeine contains codeine, a pain reliever that can gently raise a brain chemical called serotonin. Cocaine also pushes serotonin up. When two things raise serotonin at the same time, there is a chance it can climb too high, which is called serotonin syndrome. Warning signs include feeling agitated or confused, a fast heartbeat, sweating, shaking, muscle twitching, or fever.
This warning is based on theory more than firm proof, so please do not panic. The most important step is to be honest with your pharmacist or doctor about everything you take so they can watch you closely and keep you safe.
Interaction: additive serotonergic effects between codeine (in the acetaminophen/codeine product) and cocaine, raising the theoretical risk of serotonin syndrome.
- Direction: additive PD effect; both agents can increase central serotonergic activity.
- Evidence: theoretical; documented with opioids plus serotonergic drugs generally.
- Onset: unspecified; highest concern at initiation and dose changes.
- Management: if used together, observe for autonomic instability, neuromuscular abnormalities (clonus, hyperreflexia, rigidity), and altered mental status. Discontinue codeine if serotonin syndrome is suspected and treat supportively.
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
The main tool here is close observation, especially when codeine is started or its dose changes.
- Keep taking both only as prescribed. Do not start, stop, or change either one on your own.
- Tell your care team you take (or have taken) cocaine so they can monitor you more closely.
- Watch for agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching, or fever, and seek help promptly if these appear.
- Your team may stop the codeine if signs of serotonin syndrome show up.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
Common questions
Can I take Cocaine and Acetaminophen And Codeine together?
Combining codeine with cocaine can theoretically raise serotonin too high; keep your care team informed and watch for symptoms like agitation, sweating, shaking, or fever. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cocaine 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 Cocaine and Acetaminophen And Codeine interaction managed?
The main tool here is close observation, especially when codeine is started or its dose changes. Keep taking both only as prescribed. Do not start, stop, or change either one on your own. Tell your care team you take (or have taken) cocaine so they can monitor you more closely. Watch for agitation, confusion, fast heartbeat, sweating, shivering, muscle twitching, or fever, and seek help promptly i… 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 Cocaine 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
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