Codeine and Bupropion Interaction
Drug interaction information between Codeine and Bupropion.
Codeine and Bupropion have a documented minor interaction in FDA labeling.
FDA drug labeling documents a minor-severity interaction between Codeine and Bupropion. 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
Bupropion blocks the body from changing codeine into morphine, which is the active part that relieves pain. This can make the medicine less effective or cause withdrawal symptoms.
What To Do
Your doctor may need to adjust your dose or monitor you closely to ensure your pain is still being managed.
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
- Fluoxetine minor
- Trazodone minor
- Tramadol minor
- Cyclobenzaprine minor
- Oxycodone minor
Bupropion Also Interacts With
- Tranylcypromine major
- Theophylline moderate
- Isavuconazonium moderate
- Metoprolol minor
- Sertraline minor
Frequently Asked Questions
Can I take Codeine and Bupropion together?
This is a minor interaction. Your doctor may need to adjust your dose or monitor you closely to ensure your pain is still being managed.
How serious is the interaction between Codeine and Bupropion?
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 Bupropion interact?
Bupropion blocks the body from changing codeine into morphine, which is the active part that relieves pain. This can make the medicine less effective or cause withdrawal symptoms.
Understanding the Codeine and Bupropion 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 Bupropion belongs to the Norepinephrine-Dopamine Reuptake Inhibitor (NDRI) class - two categories that can collide when co-prescribed. The mechanism described in FDA labeling is: Bupropion blocks the body from changing codeine into morphine, which is the active part that relieves pain. 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 Bupropion has 35. 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: Your doctor may need to adjust your dose or monitor you closely to ensure your pain is still being managed. 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 Bupropion 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.