Drug interactions
Duloxetine + Nefazodone
Severity: Major
Duloxetine 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
Nefazodone inhibits serotonin reuptake and blocks 5-HT2A receptors, so combining it with duloxetine increases the risk of serotonin syndrome. Nefazodone also strongly inhibits CYP3A4 and has hepatotoxicity concerns, which complicate the combination further.
What this interaction means in plain words
Duloxetine 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 from combined serotonin reuptake inhibition.
What to do
Avoid combining the two antidepressants. If a switch is needed, taper one agent and monitor for serotonin toxicity during the 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 Duloxetine
- Duloxetine + Isocarboxazid Contraindicated
- Duloxetine + Linezolid Contraindicated
- Duloxetine + Methylene blue Contraindicated
- Duloxetine + Phenelzine Contraindicated
- Duloxetine + Procarbazine Contraindicated
- Duloxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Duloxetine with Nefazodone?
MediHelp rates the interaction as major. Duloxetine 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. Nefazodone inhibits serotonin reuptake and blocks 5-HT2A receptors, so combining it with duloxetine increases the risk of serotonin syndrome. Nefazodone also strongly inhibits CYP3A4 and has hepatotoxicity concerns, which complicate the combination further.
How serious is the interaction between Duloxetine 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 antidepressants. If a switch is needed, taper one agent and monitor for serotonin toxicity during the overlap.
What other medicines interact with Duloxetine?
MediHelp also lists interactions of Duloxetine with, for example, Isocarboxazid, Linezolid, Methylene blue. The full list is on the Duloxetine page.
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