Drug interactions
Fluoxetine + Nefazodone
Severity: Major
Fluoxetine and Nefazodone: 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 drugs enhance serotonergic neurotransmission, so combined use raises the risk of serotonin syndrome. Nefazodone also strongly inhibits CYP3A4 and may increase exposure to other drugs, and fluoxetine inhibits some enzymes that clear nefazodone.
What this interaction means in plain words
Fluoxetine and Nefazodone 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.
Why it happens
Additive serotonergic effects with possible pharmacokinetic interactions via CYP inhibition.
What to do
Avoid combining the two. If switching, allow a washout appropriate to fluoxetine's long half-life and monitor for serotonin toxicity.
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
Frequently asked questions
Can I take Fluoxetine with Nefazodone?
MediHelp rates the interaction as major. Fluoxetine and Nefazodone 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 drugs enhance serotonergic neurotransmission, so combined use raises the risk of serotonin syndrome. Nefazodone also strongly inhibits CYP3A4 and may increase exposure to other drugs, and fluoxetine inhibits some enzymes that clear nefazodone.
How serious is the interaction between Fluoxetine and Nefazodone?
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 combining the two. If switching, allow a washout appropriate to fluoxetine's long half-life and monitor for serotonin toxicity.
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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