Drug interactions
Clomipramine + Fluoxetine
Severity: Major
Clomipramine 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 its metabolite norfluoxetine strongly inhibit CYP2D6, markedly raising clomipramine's metabolite exposure, and both drugs are serotonergic. This increases the risk of serotonin syndrome, seizures and cardiac toxicity, and the effect persists for weeks after stopping fluoxetine.
What this interaction means in plain words
Clomipramine 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.
Clomipramine belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
Potent CYP2D6 inhibition by fluoxetine plus additive serotonergic reuptake inhibition.
What to do
Avoid the combination; if it is unavoidable, use a much lower clomipramine dose with plasma level and ECG monitoring and observe for serotonin toxicity.
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 Clomipramine
- Arsenic trioxide + Clomipramine Contraindicated
- Clomipramine + Dofetilide Contraindicated
- Clomipramine + Droperidol Contraindicated
- Clomipramine + Isocarboxazid Contraindicated
- Clomipramine + Methylene blue Contraindicated
- Clomipramine + Pentamidine Contraindicated
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 Clomipramine with Fluoxetine?
MediHelp rates the interaction as major. Clomipramine 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 its metabolite norfluoxetine strongly inhibit CYP2D6, markedly raising clomipramine's metabolite exposure, and both drugs are serotonergic. This increases the risk of serotonin syndrome, seizures and cardiac toxicity, and the effect persists for weeks after stopping fluoxetine.
How serious is the interaction between Clomipramine 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: Avoid the combination; if it is unavoidable, use a much lower clomipramine dose with plasma level and ECG monitoring and observe for serotonin toxicity.
What other medicines interact with Clomipramine?
MediHelp also lists interactions of Clomipramine with, for example, Arsenic trioxide, Dofetilide, Droperidol. The full list is on the Clomipramine page.
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