Drug interactions
Fluoxetine + Propafenone
Severity: Major
Fluoxetine and Propafenone: 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 is a strong CYP2D6 inhibitor and can sharply raise propafenone levels, increasing the risk of conduction slowing and proarrhythmia. Propafenone may in turn inhibit CYP2D6 and raise fluoxetine levels, and both drugs may prolong the QT interval.
What this interaction means in plain words
Fluoxetine and Propafenone 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; Propafenone belongs to Cardiovascular.
Why it happens
Mutual CYP2D6 inhibition with additive QT and conduction effects.
What to do
Avoid the combination where possible, or use an antidepressant with less CYP2D6 inhibition such as sertraline or citalopram at a low dose. If combined, reduce the propafenone dose and monitor ECG for QRS and QTc widening.
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 Propafenone
- Dofetilide + Propafenone Contraindicated
- Dronedarone + Propafenone Contraindicated
- Nilotinib + Propafenone Contraindicated
- Nirmatrelvir / ritonavir + Propafenone Contraindicated
- Nirmatrelvir + Propafenone Contraindicated
- Pimozide + Propafenone 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 Propafenone?
MediHelp rates the interaction as major. Fluoxetine and Propafenone 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 is a strong CYP2D6 inhibitor and can sharply raise propafenone levels, increasing the risk of conduction slowing and proarrhythmia. Propafenone may in turn inhibit CYP2D6 and raise fluoxetine levels, and both drugs may prolong the QT interval.
How serious is the interaction between Fluoxetine and Propafenone?
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, or use an antidepressant with less CYP2D6 inhibition such as sertraline or citalopram at a low dose. If combined, reduce the propafenone dose and monitor ECG for QRS and QTc widening.
What other medicines interact with Propafenone?
MediHelp also lists interactions of Propafenone with, for example, Dofetilide, Dronedarone, Nilotinib. The full list is on the Propafenone page.
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