Drug interactions
Fluoxetine + Protriptyline
Severity: Major
Fluoxetine and Protriptyline: major interaction.
Last updated Sources: UK SmPC
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 strongly inhibits CYP2D6 and raises tricyclic concentrations, increasing the risk of anticholinergic effects, cardiac conduction changes and seizures. The combination also increases serotonergic effects and the risk of serotonin syndrome.
What this interaction means in plain words
Fluoxetine and Protriptyline 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.
Why it happens
CYP2D6 inhibition raising protriptyline levels, plus additive serotonergic activity.
What to do
Avoid the combination where possible. If used, start protriptyline at a low dose, monitor ECG and plasma levels, and watch 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
- Fluoxetine 10 mg hard capsules - SmPC sections 4.3/4.5 (class statement: tricyclic antidepressants; "tricyclic antidepressants, certain antimicrobial agents") — electronic medicines compendium (UK SmPC)
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 Protriptyline?
MediHelp rates the interaction as major. Fluoxetine and Protriptyline 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 strongly inhibits CYP2D6 and raises tricyclic concentrations, increasing the risk of anticholinergic effects, cardiac conduction changes and seizures. The combination also increases serotonergic effects and the risk of serotonin syndrome.
How serious is the interaction between Fluoxetine and Protriptyline?
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 protriptyline at a low dose, monitor ECG and plasma levels, and watch for serotonin toxicity.
What other medicines interact with Fluoxetine?
MediHelp also lists interactions of Fluoxetine with, for example, Isocarboxazid, Mavacamten, Methylene blue. The full list is on the Fluoxetine page.
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