Drug interactions
Desipramine + Fluoxetine
Severity: Major
Desipramine 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 strongly inhibit CYP2D6, which can multiply desipramine concentrations and cause tricyclic toxicity including arrhythmias and seizures. Additive serotonergic effects add risk of serotonin syndrome, and the inhibition persists for weeks after fluoxetine is stopped.
What this interaction means in plain words
Desipramine 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.
Desipramine belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
Strong CYP2D6 inhibition by fluoxetine and norfluoxetine plus additive serotonergic activity.
What to do
Avoid if possible; if combined, use a much lower desipramine dose, monitor plasma levels and ECG, and watch for serotonin syndrome.
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 Desipramine
- Desipramine + Disopyramide Contraindicated
- Desipramine + Dofetilide Contraindicated
- Desipramine + Ibutilide Contraindicated
- Desipramine + Isocarboxazid Contraindicated
- Desipramine + Methylene blue Contraindicated
- Desipramine + 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 Desipramine with Fluoxetine?
MediHelp rates the interaction as major. Desipramine 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 strongly inhibit CYP2D6, which can multiply desipramine concentrations and cause tricyclic toxicity including arrhythmias and seizures. Additive serotonergic effects add risk of serotonin syndrome, and the inhibition persists for weeks after fluoxetine is stopped.
How serious is the interaction between Desipramine 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 if possible; if combined, use a much lower desipramine dose, monitor plasma levels and ECG, and watch for serotonin syndrome.
What other medicines interact with Desipramine?
MediHelp also lists interactions of Desipramine with, for example, Disopyramide, Dofetilide, Ibutilide. The full list is on the Desipramine page.
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