Drug interactions
Fluoxetine + Trazodone
Severity: Major
Fluoxetine and Trazodone: 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 activity, so combined use raises the risk of serotonin syndrome. Fluoxetine also inhibits CYP2D6 and CYP3A4 and can raise levels of trazodone's active metabolite, increasing sedation, orthostasis and QT effects.
What this interaction means in plain words
Fluoxetine and Trazodone 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; Trazodone belongs to Central Nervous System.
Why it happens
Additive serotonergic effects with fluoxetine inhibition of trazodone metabolism.
What to do
If both are needed, use low trazodone doses such as for insomnia and monitor for serotonin toxicity, excessive sedation and hypotension. Check ECG in patients with other QT risk factors.
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 Trazodone
- Arsenic trioxide + Trazodone Contraindicated
- Ibutilide + Trazodone Contraindicated
- Isocarboxazid + Trazodone Contraindicated
- Levoketoconazole + Trazodone Contraindicated
- Methylene blue + Trazodone Contraindicated
- Phenelzine + Trazodone Contraindicated
Frequently asked questions
Can I take Fluoxetine with Trazodone?
MediHelp rates the interaction as major. Fluoxetine and Trazodone 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 activity, so combined use raises the risk of serotonin syndrome. Fluoxetine also inhibits CYP2D6 and CYP3A4 and can raise levels of trazodone's active metabolite, increasing sedation, orthostasis and QT effects.
How serious is the interaction between Fluoxetine and Trazodone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: If both are needed, use low trazodone doses such as for insomnia and monitor for serotonin toxicity, excessive sedation and hypotension. Check ECG in patients with other QT risk factors.
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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