Drug interactions
Bupropion + Fluoxetine
Severity: Major
Bupropion and Fluoxetine: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Fluoxetine and its metabolite inhibit CYP2D6 and bupropion also inhibits CYP2D6, so exposure to shared substrates may increase. Fluoxetine may raise bupropion's active metabolite exposure through effects on its metabolism, and both drugs lower the seizure threshold. Seizure risk is increased.
What this interaction means in plain words
Bupropion and Fluoxetine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Bupropion belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
Additive seizure-threshold lowering with mutual metabolic effects via CYP2B6 and CYP2D6 pathways.
What to do
Avoid if possible; if combined use the lowest bupropion dose with slow titration. Monitor for seizures, agitation and serotonergic symptoms.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Bupropion
- Bupropion + Isocarboxazid Contraindicated
- Bupropion + Linezolid Contraindicated
- Bupropion + Phenelzine Contraindicated
- Bupropion + Rasagiline Contraindicated
- Bupropion + Selegiline Contraindicated
- Bupropion + Selegiline transdermal Contraindicated
Other interactions of Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Bupropion with Fluoxetine?
MediHelp rates the interaction as major. Bupropion and Fluoxetine can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Fluoxetine and its metabolite inhibit CYP2D6 and bupropion also inhibits CYP2D6, so exposure to shared substrates may increase. Fluoxetine may raise bupropion's active metabolite exposure through effects on its metabolism, and both drugs lower the seizure threshold. Seizure risk is increased.
How serious is the interaction between Bupropion and Fluoxetine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid if possible; if combined use the lowest bupropion dose with slow titration. Monitor for seizures, agitation and serotonergic symptoms.
What other medicines interact with Bupropion?
MediHelp also lists interactions of Bupropion with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Bupropion page.
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