Drug interactions
Doxepin + Fluoxetine
Severity: Major
Doxepin and Fluoxetine: 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 strongly inhibits CYP2D6 and can markedly raise doxepin concentrations, leading to sedation, anticholinergic effects and cardiac conduction changes. Both drugs are serotonergic, so serotonin syndrome is also possible.
What this interaction means in plain words
Doxepin 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.
Doxepin belongs to Dermatology; Fluoxetine belongs to Central Nervous System.
Why it happens
CYP2D6 (and CYP2C19) inhibition by fluoxetine reduces doxepin clearance, with additive serotonergic effects.
What to do
Avoid if possible. If combined, use a low doxepin dose, titrate slowly, and monitor for TCA toxicity, serotonin syndrome and ECG changes.
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
Other interactions of Doxepin
- Doxepin + Isocarboxazid Contraindicated
- Doxepin + Phenelzine Contraindicated
- Doxepin + Procarbazine Contraindicated
- Doxepin + Safinamide Contraindicated
- Doxepin + Selegiline Contraindicated
- Doxepin + Tranylcypromine Contraindicated
Frequently asked questions
Can I take Doxepin with Fluoxetine?
MediHelp rates the interaction as major. Doxepin 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 strongly inhibits CYP2D6 and can markedly raise doxepin concentrations, leading to sedation, anticholinergic effects and cardiac conduction changes. Both drugs are serotonergic, so serotonin syndrome is also possible.
How serious is the interaction between Doxepin 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, use a low doxepin dose, titrate slowly, and monitor for TCA toxicity, serotonin syndrome and ECG changes.
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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