Acetaminophen And Codeine and Moclobemide: 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
Moclobemide
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.
These two medicines should not be taken together. Codeine is a painkiller that only works after your body turns it into morphine. Moclobemide (an antidepressant in the MAOI family) blocks the enzyme that does this conversion. So your pain relief may be weaker, while codeine itself builds up in your system.
On top of that, both medicines affect the brain chemical serotonin. Combining them raises the risk of a dangerous reaction called serotonin syndrome, which can cause agitation, fast heart rate, sweating, shaking, and confusion. Please don't stop or change anything on your own. Talk with your pharmacist or doctor, who can safely choose a different pain option for you.
Contraindicated combination. Two concerns:
- Serotonergic: Moclobemide is an MAOI; additive serotonergic effects with codeine raise the risk of serotonin syndrome.
- PK: Codeine is a prodrug requiring CYP2D6 activation to morphine. Moclobemide inhibits CYP2D6, increasing parent codeine exposure while reducing active morphine formation (attenuated analgesia).
Evidence: theoretical. Management: Avoid the combination. Discontinue moclobemide 14 days before initiating codeine. If urgent opioid needed, select an alternative (oxycodone, hydrocodone, oxymorphone, buprenorphine), begin with an immediate-release test dose and titrate carefully while monitoring blood pressure and signs of CNS and respiratory depression.
What happens
Increased risk of serotonin syndrome, increased codeine exposure and reduced active metabolite (morphine) exposure
Interaction Deep Dive
Combining codeine with moclobemide, which acts as both an MAOI and a CYP2D6 inhibitor, is contraindicated. Before starting codeine, moclobemide must be stopped for 14 days. When opioid therapy cannot wait, 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 keeping watch on blood pressure as well as signs and symptoms of CNS and respiratory depression12.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of CYP2D6-mediated codeine metabolism
How to manage this interaction
This pairing is contraindicated, so your care team will generally avoid using them together. Keep taking what is currently prescribed and do not stop anything on your own; instead, raise this with your pharmacist or prescriber so they can plan a safe path.
- Because of how these drugs interact, moclobemide is typically stopped about 14 days before starting codeine.
- If pain relief is urgently needed, your team may choose a different opioid (such as oxycodone, hydrocodone, oxymorphone, or buprenorphine).
- They may start with a small test dose, adjust and individualize it, and monitor your blood pressure, alertness, and breathing closely.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Moclobemide together?
Codeine and moclobemide should not be used together because of a serious serotonin syndrome risk plus weaker, unpredictable pain relief; contact your pharmacist or doctor to arrange a safer plan. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Moclobemide 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 Moclobemide interaction managed?
This pairing is contraindicated, so your care team will generally avoid using them together. Keep taking what is currently prescribed and do not stop anything on your own; instead, raise this with your pharmacist or prescriber so they can plan a safe path. Because of how these drugs interact, moclobemide is typically stopped about 14 days before starting codeine. If pain relief is urgently needed,… 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 Moclobemide 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 (2)
- 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 Moclobemide
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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.
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