Drug interactions
Fluoxetine + Sertraline
Severity: Major
Fluoxetine and Sertraline: 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, so combined use increases the risk of serotonin syndrome. Sertraline weakly inhibits CYP2D6 and fluoxetine inhibits several enzymes, so concentrations of each may increase.
What this interaction means in plain words
Fluoxetine and Sertraline 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; Sertraline belongs to Central Nervous System.
Why it happens
Additive serotonin reuptake inhibition with some cytochrome P450 inhibition.
What to do
Avoid combining two SSRIs; use one agent and cross-taper when switching, allowing 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 Sertraline
- Isocarboxazid + Sertraline Contraindicated
- Methylene blue + Sertraline Contraindicated
- Phenelzine + Sertraline Contraindicated
- Pimozide + Sertraline Contraindicated
- Selegiline transdermal + Sertraline Contraindicated
- Selegiline + Sertraline Contraindicated
Frequently asked questions
Can I take Fluoxetine with Sertraline?
MediHelp rates the interaction as major. Fluoxetine and Sertraline 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, so combined use increases the risk of serotonin syndrome. Sertraline weakly inhibits CYP2D6 and fluoxetine inhibits several enzymes, so concentrations of each may increase.
How serious is the interaction between Fluoxetine and Sertraline?
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 SSRIs; use one agent and cross-taper when switching, allowing 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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