Drug interactions
Doxepin + Venlafaxine
Severity: Major
Doxepin and Venlafaxine: 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
Venlafaxine weakly inhibits CYP2D6 and may raise doxepin concentrations, while both drugs enhance serotonergic and noradrenergic activity. This increases the risk of serotonin syndrome, anticholinergic effects and cardiac conduction effects.
What this interaction means in plain words
Doxepin and Venlafaxine 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; Venlafaxine belongs to Central Nervous System.
Why it happens
Additive serotonin and norepinephrine reuptake inhibition, with possible CYP2D6 inhibition raising doxepin levels.
What to do
Avoid the combination where possible; if used, start with low doses of doxepin and monitor for serotonin toxicity 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 Venlafaxine
- Isocarboxazid + Venlafaxine Contraindicated
- Methylene blue + Venlafaxine Contraindicated
- Phenelzine + Venlafaxine Contraindicated
- Procarbazine + Venlafaxine Contraindicated
- Rasagiline + Venlafaxine Contraindicated
- Safinamide + Venlafaxine 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 Venlafaxine?
MediHelp rates the interaction as major. Doxepin and Venlafaxine 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. Venlafaxine weakly inhibits CYP2D6 and may raise doxepin concentrations, while both drugs enhance serotonergic and noradrenergic activity. This increases the risk of serotonin syndrome, anticholinergic effects and cardiac conduction effects.
How serious is the interaction between Doxepin and Venlafaxine?
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 used, start with low doses of doxepin and monitor for serotonin toxicity and ECG changes.
What other medicines interact with Venlafaxine?
MediHelp also lists interactions of Venlafaxine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Venlafaxine page.
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