Acetaminophen And Codeine and Tranylcypromine: 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
Tranylcypromine
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.
Let me walk you through this one. Tranylcypromine (Parnate) is a type of antidepressant called an MAO inhibitor, and codeine is an opioid pain reliever (often combined with acetaminophen/Tylenol). Taking these two together is considered not safe to combine.
Together they can build up too much of a brain chemical called serotonin, which can cause a dangerous reaction (fast heart rate, high fever, shaking, confusion). They can also both slow down your brain and breathing too much. This is a serious combination, so please do not start, stop, or change either medicine on your own. Talk with your pharmacist or doctor, who can safely plan a different pain option for you.
Contraindicated combination. Tranylcypromine, a nonselective MAO inhibitor, plus codeine (a serotonergic opioid CNS depressant) produces additive risk of serotonin syndrome and additive CNS/respiratory depression.
- Mechanism: additive serotonergic effects and additive CNS depression.
- Direction/onset: increased effect; onset unspecified.
- Evidence: theoretical, but severity is contraindicated.
Management: Avoid concurrent use. Discontinue the serotonergic agent and wait at least 1 week or 4 to 5 half-lives (whichever is longer) before initiating tranylcypromine. MAO inhibition may persist up to 10 days after stopping tranylcypromine. If urgent opioid use is needed, select an alternative opioid (oxycodone, hydrocodone, oxymorphone, buprenorphine), use immediate-release test doses, titrate carefully, and monitor blood pressure and CNS/respiratory status.
What happens
Increased risk of serotonin syndrome and an increased risk of CNS depression
Interaction Deep Dive
Combining tranylcypromine with codeine, a serotonergic CNS depressant, is contraindicated because it can produce severe or potentially fatal reactions such as serotonin syndrome, and it can additionally heighten the likelihood of CNS depression. Before starting tranylcypromine, stop the serotonergic drug and allow at least 1 week or 4 to 5 half-lives of that agent to pass, whichever interval is longer. Even after tranylcypromine is stopped, the risk of interaction continues until MAO activity has adequately recovered, since MAO inhibition can last for as long as 10 days after discontinuation4. When opioid therapy cannot be delayed, select a different opioid (for example, oxyCODONE, HYDROcodone, oxyMORphone, or buprenorphine), begin with test doses of an immediate-release formulation, and titrate the dose cautiously while watching blood pressure along with signs and symptoms of CNS and respiratory depression 123.
Why it happens (mechanism)
Additive serotonergic effects; additive CNS depression
How to manage this interaction
This pairing is generally avoided, so the most important step is letting your care team coordinate the timing and pain plan.
- Keep taking your medicines as prescribed and do not stop either one on your own.
- Your team typically separates these medicines in time. After stopping tranylcypromine, its effect can linger for up to about 10 days, and the same caution applies before restarting it.
- If you need pain relief, your prescriber may choose a different opioid and start low, adjusting the dose while watching your blood pressure and breathing.
Ask your pharmacist or doctor before combining these, and get help right away for confusion, fever, shaking, or trouble breathing.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Tranylcypromine together?
Codeine (with acetaminophen) and tranylcypromine (Parnate) should not be used together because of the risk of serotonin syndrome and dangerous slowing of breathing; let your doctor or pharmacist arrange safe timing or a different pain medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Tranylcypromine 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 Tranylcypromine interaction managed?
This pairing is generally avoided, so the most important step is letting your care team coordinate the timing and pain plan. Keep taking your medicines as prescribed and do not stop either one on your own. Your team typically separates these medicines in time. After stopping tranylcypromine, its effect can linger for up to about 10 days, and the same caution applies before restarting it. If you ne… 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 Tranylcypromine 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 (4)
- 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
- Product Information: Tranylcypromine oral tablets, tranylcypromine oral tablets. Solco Healthcare US, LLC (per DailyMed), Somerset, NJ, 2024. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Tranylcypromine
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