Codeine and Fluoxetine Interaction
Drug interaction information between Codeine and Fluoxetine.
Codeine and Fluoxetine have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine and Fluoxetine. Major interactions are generally avoided, moderate ones may need monitoring or a dose adjustment, and minor ones are usually low-risk. This page shows the documented mechanism and guidance. Label-documented interactions are not a complete safety review, so always confirm your own medications with a pharmacist or doctor. Educational information, not medical advice.
How They Interact
Fluoxetine prevents codeine from being converted into its active form, morphine. This can lead to poor pain control or cause you to feel symptoms of opioid withdrawal.
What To Do
Tell your doctor if your pain is not well-controlled, as they may need to change your medication or dosage.
FDA Label Information
The concomitant use of acetaminophen and codeine phosphate tablets and CYP2D6 inhibitors (e.g., paroxetine, fluoxetine, bupropion, quinidine) can increase the plasma concentration of codeine, but can decrease the plasma concentration of active metabolite morphine, which could result in reduced analgesic efficacy or symptoms of opioid withdrawal, particularly when an inhibitor is added after a stable dose of acetaminophen and codeine phosphate tablets is achieved (see CLINICAL PHARMACOLOGY ).
Codeine Also Interacts With
- Bupropion minor
- Trazodone minor
- Tramadol minor
- Cyclobenzaprine minor
- Oxycodone minor
Fluoxetine Also Interacts With
- Aspirin major
- Warfarin major
- Olanzapine major
- Pimozide major
- Thioridazine major
Frequently Asked Questions
Can I take Codeine and Fluoxetine together?
This is a minor interaction. Tell your doctor if your pain is not well-controlled, as they may need to change your medication or dosage.
How serious is the interaction between Codeine and Fluoxetine?
This interaction is classified as "minor" severity by the FDA. Minor interactions are unlikely to cause significant problems but should still be mentioned to your healthcare provider.
Why do Codeine and Fluoxetine interact?
Fluoxetine prevents codeine from being converted into its active form, morphine. This can lead to poor pain control or cause you to feel symptoms of opioid withdrawal.
Understanding the Codeine and Fluoxetine Interaction
FDA-approved prescribing information for these two drugs flags their combination as a minor-severity interaction. Codeine belongs to the Opioid Analgesic class and Fluoxetine belongs to the Selective Serotonin Reuptake Inhibitor (SSRI) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Fluoxetine prevents codeine from being converted into its active form, morphine. Severity tiers matter: major flags generally advise avoidance, moderate flags often require monitoring or dose adjustment, and minor flags may only call for awareness.
Context around a specific patient determines real-world impact. Codeine has 27 total documented interactions on file in this dataset, and Fluoxetine has 68. Each additional medication compounds the interaction surface, which is why pharmacists run full-profile checks rather than evaluating one pair at a time. FDA-derived guidance for this pair is: Tell your doctor if your pain is not well-controlled, as they may need to change your medication or dosage. Timing of doses, renal and hepatic function, age, and other concurrent prescriptions all shape whether a labeled interaction matters clinically.
An interaction flag is not a verdict. A large share of labeled interactions are managed routinely in clinical practice, the fix may be as simple as spacing doses or adding a monitoring test. Others require the prescriber to choose a different medication entirely. This page surfaces FDA-sourced labeling and openFDA data for educational purposes only; it is not medical advice and cannot account for your full clinical picture. Never start, stop, or adjust either Codeine or Fluoxetine based on a web page, speak with your prescriber or pharmacist before making any change.
Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. Always consult your healthcare provider about drug interactions.
Read our methodology - how this data is sourced, computed, and verified.