Drug interactions
Fluoxetine + Paroxetine
Severity: Major
Fluoxetine and Paroxetine: 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
Both are SSRIs and combined use increases the risk of serotonin syndrome. Both are strong CYP2D6 inhibitors and paroxetine is itself metabolized by CYP2D6, so fluoxetine can raise paroxetine concentrations.
What this interaction means in plain words
Fluoxetine and Paroxetine 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 belongs to Central Nervous System; Paroxetine belongs to Central Nervous System.
Why it happens
Additive serotonin reuptake inhibition with fluoxetine inhibition of CYP2D6-mediated paroxetine clearance.
What to do
Avoid using two SSRIs together; switch to a single agent with an appropriate taper, accounting for fluoxetine's long half-life. Monitor for serotonin toxicity during any overlap.
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 Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Other interactions of Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Fluoxetine with Paroxetine?
MediHelp rates the interaction as major. Fluoxetine and Paroxetine 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. Both are SSRIs and combined use increases the risk of serotonin syndrome. Both are strong CYP2D6 inhibitors and paroxetine is itself metabolized by CYP2D6, so fluoxetine can raise paroxetine concentrations.
How serious is the interaction between Fluoxetine and Paroxetine?
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 using two SSRIs together; switch to a single agent with an appropriate taper, accounting for fluoxetine's long half-life. Monitor for serotonin toxicity during any overlap.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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