Phenelzine 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
Phenelzine
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 pain medicine Tylenol with Codeine and your antidepressant phenelzine (Nardil) should not be taken together. Both can raise serotonin, a brain chemical. When too much builds up, it can cause a dangerous reaction called serotonin syndrome, with symptoms like agitation, fast heartbeat, sweating, shaking, high fever, and confusion.
Phenelzine is a strong MAOI, and its effect lingers, so a wait of about two weeks after stopping it is usually needed before codeine is safe. Please don't change anything on your own. Talk with your pharmacist or doctor. They can plan the timing safely or pick a safer pain option for you.
Contraindicated combination. Codeine plus the MAOI phenelzine carries a risk of serotonin syndrome via additive serotonergic effects. Evidence is theoretical, but the severity warrants avoidance.
- Direction/mechanism: additive serotonergic activity, not a CYP-based PK interaction.
- Management: discontinue MAOI at least 14 days before starting codeine.
- If urgent opioid needed: select an alternative (oxycodone, hydrocodone, oxymorphone, buprenorphine), begin with an immediate-release test dose, titrate cautiously.
- Monitor: blood pressure, and for CNS and respiratory depression, plus signs of serotonin toxicity (clonus, hyperthermia, autonomic instability, agitation).
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Because of the risk of serotonin syndrome, giving codeine together with an MAOI is contraindicated. An MAOI should be stopped 14 days prior to starting codeine. When opioid therapy cannot wait, select a different opioid (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. Keep taking your medications as prescribed for now, but raise this with your prescriber or pharmacist promptly so they can plan safely.
- Your care team will usually allow about 14 days after stopping phenelzine before codeine is started.
- If pain relief is urgently needed, they may choose a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), starting with a small test dose and adjusting carefully.
- Expect closer monitoring of your blood pressure, breathing, and alertness during any transition.
Do not start, stop, or change either medicine on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Phenelzine and Acetaminophen And Codeine together?
Do not use codeine-containing pain medicine with phenelzine because of serotonin syndrome risk; contact your doctor or pharmacist, who can allow a 14-day gap after phenelzine or choose a safer opioid. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Phenelzine and Acetaminophen And Codeine 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 Phenelzine and Acetaminophen And Codeine interaction managed?
This combination should be avoided. Keep taking your medications as prescribed for now, but raise this with your prescriber or pharmacist promptly so they can plan safely. Your care team will usually allow about 14 days after stopping phenelzine before codeine is started. If pain relief is urgently needed, they may choose a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenor… 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 Phenelzine 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: 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
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