Isocarboxazid 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
Isocarboxazid
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. Isocarboxazid (Marplan) is a strong antidepressant called an MAOI, and codeine (found in your acetaminophen with codeine) can also affect a brain chemical called serotonin. When both are on board, serotonin can climb too high and cause a dangerous reaction called serotonin syndrome. Signs can include agitation, a fast heartbeat, sweating, shaking, high fever, or confusion.
The good news is your care team can plan around this safely. Please don't start or stop anything on your own. Talk with your doctor or pharmacist so they can pick a safe pain option and time your medicines correctly.
Contraindicated combination. Codeine (a prodrug activated via CYP2D6 to morphine) also has serotonergic activity; combined with the MAOI isocarboxazid, additive serotonergic effects raise the risk of serotonin syndrome.
- Direction: additive serotonin toxicity (not a PK clearance change).
- Evidence: theoretical, but severity is contraindicated given potential lethality.
- Onset: unspecified.
Management: Do not co-administer. Discontinue the MAOI at least 14 days before initiating codeine. If urgent analgesia is required, select an alternative opioid (oxycodone, hydrocodone, oxymorphone, buprenorphine), use immediate-release test doses, titrate carefully, and monitor blood pressure plus signs of CNS and respiratory depression.
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Because it carries a risk of serotonin syndrome, giving codeine together with an MAOI is contraindicated. Any MAOI should be stopped 14 days prior to starting codeine. When an opioid is required urgently, select a different agent (for example, oxyCODONE, HYDROcodone, oxyMORphone, or buprenorphine), begin with test doses using an immediate-release formulation, 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 pairing is avoided. Keep taking exactly what your prescriber has already told you, and never start or stop either drug on your own.
- Your care team will typically keep at least a 14-day gap after stopping the MAOI (isocarboxazid) before any codeine is started.
- If pain relief is urgently needed, your team may choose a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), begin with a small test dose, and monitor your blood pressure, alertness, and breathing.
Tell your pharmacist or doctor about all your medicines, and get urgent help for agitation, fever, sweating, shaking, or a racing heart.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Isocarboxazid and Acetaminophen And Codeine together?
Do not take codeine-containing painkillers with the MAOI isocarboxazid because of the risk of serotonin syndrome; your care team can arrange a safe alternative or the required 14-day gap. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Isocarboxazid 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 Isocarboxazid and Acetaminophen And Codeine interaction managed?
This pairing is avoided. Keep taking exactly what your prescriber has already told you, and never start or stop either drug on your own. Your care team will typically keep at least a 14-day gap after stopping the MAOI (isocarboxazid) before any codeine is started. If pain relief is urgently needed, your team may choose a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphi… 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 Isocarboxazid 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
Keep reading about Acetaminophen And Codeine
Keep reading about Isocarboxazid
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