Drug interactions
Clozapine + Fluoxetine
Severity: Major
Clozapine 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 and norfluoxetine inhibit CYP2D6 and to a degree CYP1A2 and CYP3A4, which can raise clozapine levels, leading to sedation, seizures, hypotension and sialorrhea. Both drugs can also prolong the QT interval.
What this interaction means in plain words
Clozapine 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.
Clozapine belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
Inhibition of clozapine metabolism by fluoxetine plus additive QT prolongation.
What to do
Monitor clozapine levels and clinical effects, and reduce the clozapine dose if toxicity appears. Obtain ECG and check electrolytes in patients with QT risk factors.
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 Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Frequently asked questions
Can I take Clozapine with Fluoxetine?
MediHelp rates the interaction as major. Clozapine 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 and norfluoxetine inhibit CYP2D6 and to a degree CYP1A2 and CYP3A4, which can raise clozapine levels, leading to sedation, seizures, hypotension and sialorrhea. Both drugs can also prolong the QT interval.
How serious is the interaction between Clozapine 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: Monitor clozapine levels and clinical effects, and reduce the clozapine dose if toxicity appears. Obtain ECG and check electrolytes in patients with QT risk factors.
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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