Drug interactions
Doxepin + Paroxetine
Severity: Major
Doxepin and Paroxetine: 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
Paroxetine strongly inhibits CYP2D6 and can markedly raise doxepin concentrations, increasing anticholinergic effects, sedation, orthostasis and cardiac conduction effects. Both drugs also enhance serotonergic activity, so serotonin syndrome is possible.
What this interaction means in plain words
Doxepin and Paroxetine 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; Paroxetine belongs to Central Nervous System.
Why it happens
Paroxetine inhibits CYP2D6-mediated doxepin metabolism, and both drugs inhibit serotonin reuptake, giving additive serotonergic effects.
What to do
Avoid the combination where possible. If it is necessary, start doxepin at a low dose, titrate slowly, and monitor for serotonin toxicity, sedation, 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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline 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 Paroxetine?
MediHelp rates the interaction as major. Doxepin and Paroxetine 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. Paroxetine strongly inhibits CYP2D6 and can markedly raise doxepin concentrations, increasing anticholinergic effects, sedation, orthostasis and cardiac conduction effects. Both drugs also enhance serotonergic activity, so serotonin syndrome is possible.
How serious is the interaction between Doxepin and Paroxetine?
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 it is necessary, start doxepin at a low dose, titrate slowly, and monitor for serotonin toxicity, sedation, and ECG changes.
What other medicines interact with Paroxetine?
MediHelp also lists interactions of Paroxetine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Paroxetine page.
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