Drug interactions
Duloxetine + Fluoxetine
Severity: Major
Duloxetine 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 strongly inhibits CYP2D6, which is one of the enzymes that clears duloxetine, so duloxetine exposure can rise. Both drugs also enhance serotonergic transmission, so the combination raises the risk of serotonin syndrome and of duloxetine adverse effects such as nausea, hypertension and bleeding.
What this interaction means in plain words
Duloxetine 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.
Duloxetine belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
Fluoxetine inhibits CYP2D6-mediated duloxetine metabolism and both drugs inhibit serotonin reuptake, giving additive serotonergic effects.
What to do
Avoid combining two serotonergic antidepressants where possible; if a switch is needed, taper one agent and allow for fluoxetine's long half-life. If used together, monitor for serotonin toxicity and blood pressure.
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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Duloxetine and Fluoxetine, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
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 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 Fluoxetine?
MediHelp rates the interaction as major. Duloxetine 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 strongly inhibits CYP2D6, which is one of the enzymes that clears duloxetine, so duloxetine exposure can rise. Both drugs also enhance serotonergic transmission, so the combination raises the risk of serotonin syndrome and of duloxetine adverse effects such as nausea, hypertension and bleeding.
How serious is the interaction between Duloxetine 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 combining two serotonergic antidepressants where possible; if a switch is needed, taper one agent and allow for fluoxetine's long half-life. If used together, monitor for serotonin toxicity and blood pressure.
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.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
