Drug interactions
Fluoxetine + Imipramine
Severity: Major
Fluoxetine and Imipramine: 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 long-lived metabolite norfluoxetine strongly inhibit CYP2D6 and also affect CYP2C19, raising imipramine and desipramine concentrations. This can produce tricyclic toxicity such as anticholinergic effects, sedation, hypotension, seizures and arrhythmias. Additive serotonergic activity also raises the risk of serotonin syndrome.
What this interaction means in plain words
Fluoxetine and Imipramine 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; Imipramine belongs to Central Nervous System.
Why it happens
Inhibition of CYP2D6 and CYP2C19 metabolism of imipramine plus additive serotonin reuptake inhibition.
What to do
Avoid the combination where possible; if used, start imipramine at a markedly reduced dose and titrate using tricyclic plasma levels and ECG. Because inhibition persists for weeks after stopping fluoxetine, continue monitoring during that period.
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 Imipramine
- Dronedarone + Imipramine Contraindicated
- Imipramine + Isocarboxazid Contraindicated
- Imipramine + Phenelzine Contraindicated
- Imipramine + Pimozide Contraindicated
- Imipramine + Rasagiline Contraindicated
- Imipramine + Safinamide 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 Fluoxetine with Imipramine?
MediHelp rates the interaction as major. Fluoxetine and Imipramine 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 long-lived metabolite norfluoxetine strongly inhibit CYP2D6 and also affect CYP2C19, raising imipramine and desipramine concentrations. This can produce tricyclic toxicity such as anticholinergic effects, sedation, hypotension, seizures and arrhythmias. Additive serotonergic activity also raises the risk of serotonin syndrome.
How serious is the interaction between Fluoxetine and Imipramine?
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 where possible; if used, start imipramine at a markedly reduced dose and titrate using tricyclic plasma levels and ECG. Because inhibition persists for weeks after stopping fluoxetine, continue monitoring during that period.
What other medicines interact with Imipramine?
MediHelp also lists interactions of Imipramine with, for example, Dronedarone, Isocarboxazid, Phenelzine. The full list is on the Imipramine page.
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