Drug interactions
Fluoxetine + Iloperidone
Severity: Major
Fluoxetine and Iloperidone: 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, the main enzyme clearing iloperidone, so iloperidone exposure rises substantially. This increases the risk of QT prolongation, sedation and orthostatic hypotension, and fluoxetine may add its own QT effect.
What this interaction means in plain words
Fluoxetine and Iloperidone 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; Iloperidone belongs to Central Nervous System.
Why it happens
Inhibition of CYP2D6-mediated iloperidone metabolism, plus additive QT effects.
What to do
Reduce the iloperidone dose by about half when starting a strong CYP2D6 inhibitor, and monitor ECG and for hypotension. Restore the dose if fluoxetine is stopped, remembering its long half-life.
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 Iloperidone
- Iloperidone + Thioridazine Contraindicated
- Alfuzosin + Iloperidone Major
- Amiodarone + Iloperidone Major
- Amisulpride + Iloperidone Major
- Amitriptyline + Iloperidone Major
- Anagrelide + Iloperidone Major
Frequently asked questions
Can I take Fluoxetine with Iloperidone?
MediHelp rates the interaction as major. Fluoxetine and Iloperidone 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, the main enzyme clearing iloperidone, so iloperidone exposure rises substantially. This increases the risk of QT prolongation, sedation and orthostatic hypotension, and fluoxetine may add its own QT effect.
How serious is the interaction between Fluoxetine and Iloperidone?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Reduce the iloperidone dose by about half when starting a strong CYP2D6 inhibitor, and monitor ECG and for hypotension. Restore the dose if fluoxetine is stopped, remembering its long half-life.
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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