Drug interactions
Fluoxetine + Perphenazine
Severity: Major
Fluoxetine and Perphenazine: 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
Perphenazine is cleared mainly by CYP2D6, which fluoxetine strongly inhibits, so perphenazine levels can increase markedly with more extrapyramidal and sedative effects. Both drugs may also prolong the QT interval.
What this interaction means in plain words
Fluoxetine and Perphenazine 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; Perphenazine belongs to Central Nervous System.
Why it happens
Fluoxetine inhibits CYP2D6 metabolism of perphenazine, with additive QT prolongation.
What to do
Start with a reduced perphenazine dose and titrate to response, monitoring for parkinsonism, akathisia and sedation. Check ECG when other QT risk factors are present.
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 Fluoxetine and Perphenazine, 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 Perphenazine
- Ibutilide + Perphenazine Contraindicated
- Perphenazine + Pimozide Contraindicated
- Perphenazine + Thioridazine Contraindicated
- Adagrasib + Perphenazine Major
- Alfentanil + Perphenazine Major
- Amiodarone + Perphenazine Major
Frequently asked questions
Can I take Fluoxetine with Perphenazine?
MediHelp rates the interaction as major. Fluoxetine and Perphenazine 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. Perphenazine is cleared mainly by CYP2D6, which fluoxetine strongly inhibits, so perphenazine levels can increase markedly with more extrapyramidal and sedative effects. Both drugs may also prolong the QT interval.
How serious is the interaction between Fluoxetine and Perphenazine?
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 with a reduced perphenazine dose and titrate to response, monitoring for parkinsonism, akathisia and sedation. Check ECG when other QT risk factors are present.
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.
