Acetaminophen And Codeine and Selegiline: 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
Selegiline
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.
These two medicines should not be taken together. Selegiline is an MAOI, a type of drug often used for Parkinson's or depression. Codeine (the pain medicine paired with acetaminophen) can raise serotonin levels in your body. When you combine them, serotonin can climb too high and cause a dangerous reaction called serotonin syndrome, with symptoms like agitation, a fast heartbeat, sweating, shivering, muscle twitching, or confusion.
The good news is that your care team can manage this safely by keeping these two apart and choosing a different pain option when one is needed. Please do not start, stop, or change either drug on your own. Talk with your pharmacist or doctor so they can plan the safest approach for you.
Combination is contraindicated. Codeine has serotonergic activity, and selegiline is an MAO inhibitor; together they carry a risk of serotonin syndrome through additive serotonergic effects (pharmacodynamic).
- Direction: Additive serotonin toxicity risk.
- Evidence: Theoretical.
- Onset: Unspecified.
- Management: Avoid concurrent use. Discontinue the MAOI at least 14 days before initiating codeine. If urgent opioid therapy is required, select an alternative opioid (eg, oxycodone, hydrocodone, oxymorphone, buprenorphine), begin with immediate-release test doses, and titrate carefully while monitoring blood pressure and for CNS and respiratory depression.
Monitor for agitation, hyperthermia, clonus, hyperreflexia, autonomic instability, and altered mental status.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Because of the risk of serotonin syndrome, taking codeine together with an MAOI is contraindicated. An MAOI must be stopped 14 days prior to starting codeine. When opioid therapy cannot wait, select a different opioid instead (for example, oxyCODONE, HYDROcodone, oxyMORphone, or buprenorphine), begin with test doses of an immediate-release preparation, and titrate the dose cautiously while watching blood pressure along with signs and symptoms of CNS and respiratory depression123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This combination should be avoided. Your care team manages this by keeping these drugs apart in time and choosing a safer pain option.
- An MAOI like selegiline is typically stopped at least 14 days before codeine is started.
- If pain relief is urgently needed, your team may pick a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), begin with a small test dose, and monitor your blood pressure, breathing, and alertness closely.
Keep taking your medicines exactly as prescribed and do not change anything on your own. Ask your pharmacist or prescriber before any new pain medicine is added so they can plan a safe alternative.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Selegiline together?
Do not take codeine with selegiline, because together they can trigger serotonin syndrome. Ask your pharmacist or doctor to arrange a safe pain-relief alternative and proper spacing between the drugs. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Selegiline interaction?
It is rated contraindicated. These should generally not be used together.
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 Selegiline interaction managed?
This combination should be avoided. Your care team manages this by keeping these drugs apart in time and choosing a safer pain option. An MAOI like selegiline is typically stopped at least 14 days before codeine is started. If pain relief is urgently needed, your team may pick a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), begin with a small test dose, and moni… 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 Selegiline 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: CARISOPRODOL, ASPIRIN, CODEINE PHOSPHATE oral tablets, carisoprodol, aspirin, codeine phosphate oral tablets. Ingenus Pharmaceuticals LLC (per DailyMed), Orlando, FL, 2021. DailyMed
- Product Information: Codeine sulfate oral solution, codeine sulfate oral solution. Hikma Pharmaceuticals USA Inc(per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Selegiline
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