Drug interactions
Fluoxetine + Trimipramine
Severity: Major
Fluoxetine and Trimipramine: 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, which can substantially raise tricyclic concentrations and cause toxicity. The combination also adds serotonergic effects, increasing the risk of serotonin syndrome.
What this interaction means in plain words
Fluoxetine and Trimipramine 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; Trimipramine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by fluoxetine reduces trimipramine clearance, with additive serotonergic effects.
What to do
Avoid the combination if possible. If it is used, start with a markedly reduced tricyclic dose, check tricyclic levels and the ECG, and monitor for anticholinergic and serotonergic 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 Trimipramine
- Disopyramide + Trimipramine Contraindicated
- Dofetilide + Trimipramine Contraindicated
- Ibutilide + Trimipramine Contraindicated
- Isocarboxazid + Trimipramine Contraindicated
- Pentamidine + Trimipramine Contraindicated
- Phenelzine + Trimipramine 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 Trimipramine?
MediHelp rates the interaction as major. Fluoxetine and Trimipramine 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, which can substantially raise tricyclic concentrations and cause toxicity. The combination also adds serotonergic effects, increasing the risk of serotonin syndrome.
How serious is the interaction between Fluoxetine and Trimipramine?
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 possible. If it is used, start with a markedly reduced tricyclic dose, check tricyclic levels and the ECG, and monitor for anticholinergic and serotonergic toxicity.
What other medicines interact with Trimipramine?
MediHelp also lists interactions of Trimipramine with, for example, Disopyramide, Dofetilide, Ibutilide. The full list is on the Trimipramine page.
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