Drug interactions
Amitriptyline + Fluoxetine
Severity: Major
Amitriptyline and Fluoxetine: major interaction.
Last updated
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 and also inhibit CYP2C19, which can markedly raise amitriptyline and nortriptyline concentrations. Together with additive serotonergic activity, this increases the risk of tricyclic toxicity, arrhythmia and serotonin syndrome.
What this interaction means in plain words
Amitriptyline 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.
Amitriptyline belongs to Central Nervous System; Fluoxetine belongs to Central Nervous System.
Why it happens
CYP2D6 and CYP2C19 inhibition by fluoxetine raises tricyclic levels, plus additive serotonin reuptake inhibition.
What to do
Avoid if possible; if combined, reduce the amitriptyline dose substantially and monitor plasma levels, ECG and serotonin toxicity signs. Effects persist for weeks after stopping fluoxetine.
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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Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + 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 Amitriptyline with Fluoxetine?
MediHelp rates the interaction as major. Amitriptyline 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 and also inhibit CYP2C19, which can markedly raise amitriptyline and nortriptyline concentrations. Together with additive serotonergic activity, this increases the risk of tricyclic toxicity, arrhythmia and serotonin syndrome.
How serious is the interaction between Amitriptyline 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, reduce the amitriptyline dose substantially and monitor plasma levels, ECG and serotonin toxicity signs. Effects persist for weeks after stopping fluoxetine.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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