Acetaminophen And Codeine and Fluvoxamine: 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
Fluvoxamine
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.
Your pain medicine contains codeine, which your body has to turn into morphine to actually relieve pain. Fluvoxamine slows down the liver enzymes that handle codeine, so the levels of codeine and its active form (morphine) can shift in either direction. That means you might get less pain relief, or you might get more of codeine's side effects like heavy drowsiness and slowed breathing.
These two medicines also both raise serotonin, so together they can rarely cause a reaction called serotonin syndrome (agitation, fast heartbeat, sweating, shivering, muscle twitching). This is a theoretical concern, not something that happens to everyone. Your care team can manage it by watching you closely and adjusting your dose. Let them know if you feel very sleepy or your pain isn't controlled.
Mechanism: Fluvoxamine inhibits CYP2D6 and CYP3A4. Codeine is a prodrug requiring CYP2D6 for conversion to morphine (active metabolite), while CYP3A4 handles a competing pathway. Net effect on morphine exposure is unpredictable (may increase or decrease), and parent codeine exposure increases. Additive serotonergic activity also applies.
- Direction: Variable analgesic efficacy (possible reduced effect/withdrawal) vs. increased opioid toxicity (respiratory depression, sedation).
- Evidence: Theoretical; severity major.
- Management: Monitor for sedation, respiratory depression, withdrawal, and serotonin syndrome, especially at initiation/titration. Adjust codeine dose as needed; discontinue codeine if serotonin syndrome is suspected.
What happens
Increased risk of serotonin syndrome, increased codeine and increased or reduced active metabolite (morphine) exposure
Interaction Deep Dive
Concomitant use of codeine with fluvoxaMINE, a CYP3A4 and CYP2D6 inhibitor, may result in increased codeine exposure and may either increase or reduce plasma concentrations of morphine, the active metabolite of codeine, thus potentially leading to reduced efficacy and withdrawal symptoms or an increased risk of adverse effects such as respiratory depression and sedation. If concomitant use is necessary, monitor patients for withdrawal symptoms, respiratory depression and sedation, and consider adjusting the codeine dose as needed. Additionally, concomitant use of opioids with serotonergic drugs has resulted in serotonin syndrome. If concomitant use is needed, carefully observe the patient, particularly during treatment initiation and dose adjustments. Discontinue codeine if serotonin syndrome is suspected123.
Why it happens (mechanism)
Additive serotonergic effects; inhibition of CYP2D6-mediated codeine metabolism; inhibition of CYP3A4-mediated metabolism of codeine
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, and don't stop either one on your own.
- Your care team may monitor you more closely, especially when starting or changing a dose.
- Your codeine dose may need to be adjusted and individualized by your team, since morphine levels can move in either direction.
- Watch for and report unusual sleepiness, slow or shallow breathing, or poor pain control and any withdrawal-like symptoms.
- Seek prompt care for signs of serotonin syndrome: agitation, fast heart rate, sweating, shivering, muscle twitching, or confusion.
Ask your pharmacist or prescriber before adding any new serotonin-affecting medicine.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Fluvoxamine together?
Combining codeine with fluvoxamine can unpredictably change your pain relief and raise the risk of sedation, slowed breathing, or serotonin syndrome, so watch for symptoms and let your care team monitor and adjust your dose. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Fluvoxamine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Fluvoxamine interaction managed?
Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise, and don't stop either one on your own. Your care team may monitor you more closely, especially when starting or changing a dose. Your codeine dose may need to be adjusted and individualized by your team, since morphine levels can move in either direction. Watch for and report unusual sleepiness, slow or sh… 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 Fluvoxamine 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: 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: Codeine sulfate oral tablets, codeine sulfate oral tablets. Hikma Pharmaceuticals USA Inc. (per FDA), Berkeley Heights, NJ, 2023. DailyMed
Keep reading about Acetaminophen And Codeine
Keep reading about Fluvoxamine
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