Drug interactions
Doxepin + Duloxetine
Severity: Major
Doxepin and Duloxetine: 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
Both drugs raise serotonin and norepinephrine, so the combination increases the risk of serotonin syndrome. Duloxetine inhibits CYP2D6 and may increase doxepin exposure, adding anticholinergic, sedative and cardiac effects.
What this interaction means in plain words
Doxepin and Duloxetine 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; Duloxetine belongs to Central Nervous System.
Why it happens
Additive monoamine reuptake inhibition with CYP2D6 inhibition by duloxetine.
What to do
Avoid combining at antidepressant doses. If low-dose doxepin is used for insomnia, monitor for serotonin toxicity and excess sedation.
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 Duloxetine
- Duloxetine + Isocarboxazid Contraindicated
- Duloxetine + Linezolid Contraindicated
- Duloxetine + Methylene blue Contraindicated
- Duloxetine + Phenelzine Contraindicated
- Duloxetine + Procarbazine Contraindicated
- Duloxetine + 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 Duloxetine?
MediHelp rates the interaction as major. Doxepin and Duloxetine 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. Both drugs raise serotonin and norepinephrine, so the combination increases the risk of serotonin syndrome. Duloxetine inhibits CYP2D6 and may increase doxepin exposure, adding anticholinergic, sedative and cardiac effects.
How serious is the interaction between Doxepin and Duloxetine?
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 at antidepressant doses. If low-dose doxepin is used for insomnia, monitor for serotonin toxicity and excess sedation.
What other medicines interact with Duloxetine?
MediHelp also lists interactions of Duloxetine with, for example, Isocarboxazid, Linezolid, Methylene blue. The full list is on the Duloxetine page.
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