Drug interactions
Fluoxetine + Perhexiline
Severity: Major
Fluoxetine and Perhexiline: 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
Perhexiline is cleared mainly by CYP2D6 and has a narrow therapeutic index. Fluoxetine is a potent CYP2D6 inhibitor and can markedly raise perhexiline levels, risking hepatotoxicity, neuropathy and hypoglycemia.
What this interaction means in plain words
Fluoxetine and Perhexiline 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
Inhibition of CYP2D6-mediated perhexiline metabolism by fluoxetine and norfluoxetine.
What to do
Avoid combining if possible; otherwise reduce the perhexiline dose and monitor plasma perhexiline concentrations and liver function. Continue monitoring for several weeks after fluoxetine is stopped because of its long half-life.
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 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 Perhexiline?
MediHelp rates the interaction as major. Fluoxetine and Perhexiline 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. Perhexiline is cleared mainly by CYP2D6 and has a narrow therapeutic index. Fluoxetine is a potent CYP2D6 inhibitor and can markedly raise perhexiline levels, risking hepatotoxicity, neuropathy and hypoglycemia.
How serious is the interaction between Fluoxetine and Perhexiline?
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 combining if possible; otherwise reduce the perhexiline dose and monitor plasma perhexiline concentrations and liver function. Continue monitoring for several weeks after fluoxetine is stopped because of its long half-life.
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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