Acetaminophen And Codeine and Procarbazine: 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
Procarbazine
No brand names on record
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.
You've been prescribed two medicines that don't mix well. Procarbazine (a chemotherapy drug) works like an MAOI, and combining it with codeine (the pain reliever paired with acetaminophen in Tylenol with Codeine) can raise the risk of a dangerous reaction called serotonin syndrome. This can cause a fast heart rate, high blood pressure, agitation, sweating, shaking, or confusion.
Because of this risk, these two are generally not used together. Please don't start, stop, or change either one on your own. Instead, talk with your doctor or pharmacist. They can pick a safer pain option and keep a close eye on you so your pain is still treated safely.
Interaction: Codeine combined with procarbazine (an MAO inhibitor) carries a risk of serotonin syndrome via additive serotonergic effects. This combination is rated contraindicated.
- Mechanism: Additive serotonergic activity; opioids with serotonergic properties plus MAOI.
- Evidence: Theoretical, but severity warrants strict avoidance.
- Management: Separate MAOI (procarbazine) and codeine by 14 days. If urgent opioid needed, select an alternative (oxycodone, hydrocodone, oxymorphone, buprenorphine), begin with immediate-release test doses, titrate carefully.
- Monitor: Blood pressure, CNS and respiratory depression, and signs of serotonin syndrome (hyperthermia, clonus, agitation, autonomic instability).
What happens
Increased risk of serotonin syndrome
Interaction Deep Dive
Combining codeine with an MAOI is contraindicated because of the risk of serotonin syndrome. 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 using an immediate-release formulation, and titrate the dose cautiously while keeping watch on blood pressure as well as signs and symptoms of CNS and respiratory depression123.
Why it happens (mechanism)
Additive serotonergic effects
How to manage this interaction
This pairing is best avoided. Here is what a care team typically does:
- Keeps procarbazine and codeine separated by about 14 days rather than using them together.
- If pain relief is urgently needed, chooses a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), starting low and titrating carefully.
- Monitors your blood pressure and watches for drowsiness, slowed breathing, or signs of serotonin syndrome.
What you should do: Don't take these together or change anything yourself. Contact your prescriber or pharmacist so they can arrange a safe pain-control plan and monitor you closely.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Procarbazine together?
Do not use codeine (in acetaminophen and codeine) together with procarbazine, as this combination can cause serotonin syndrome. Contact your doctor or pharmacist, who can choose a safer alternative and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Procarbazine 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 Procarbazine interaction managed?
This pairing is best avoided. Here is what a care team typically does: Keeps procarbazine and codeine separated by about 14 days rather than using them together. If pain relief is urgently needed, chooses a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine), starting low and titrating carefully. Monitors your blood pressure and watches for drowsiness, slowed breathing… 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 Procarbazine 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 Procarbazine
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist