Drug interactions
Fluoxetine + Trifluoperazine
Severity: Major
Fluoxetine and Trifluoperazine: 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 and can raise trifluoperazine concentrations, increasing sedation, extrapyramidal symptoms and anticholinergic effects. Both drugs also prolong the QT interval, so arrhythmia risk is additive.
What this interaction means in plain words
Fluoxetine and Trifluoperazine 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
CYP2D6 inhibition by fluoxetine reduces phenothiazine clearance, combined with additive QT prolongation.
What to do
Start trifluoperazine at a low dose and titrate slowly, watching for extrapyramidal signs and sedation. Obtain an ECG at baseline and after dose changes and correct electrolytes.
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 Trifluoperazine?
MediHelp rates the interaction as major. Fluoxetine and Trifluoperazine 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 and can raise trifluoperazine concentrations, increasing sedation, extrapyramidal symptoms and anticholinergic effects. Both drugs also prolong the QT interval, so arrhythmia risk is additive.
How serious is the interaction between Fluoxetine and Trifluoperazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Start trifluoperazine at a low dose and titrate slowly, watching for extrapyramidal signs and sedation. Obtain an ECG at baseline and after dose changes and correct electrolytes.
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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