Drug interactions
Amitriptyline + Doxepin
Severity: Major
Amitriptyline and Doxepin: major interaction.
Last updated
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 are tricyclic antidepressants, so combining them gives duplicate therapy with additive anticholinergic, sedative, cardiac conduction and QT effects. Serotonergic effects and overdose-type toxicity are also more likely.
What this interaction means in plain words
Amitriptyline and Doxepin 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.
Amitriptyline belongs to Central Nervous System; Doxepin belongs to Dermatology.
Why it happens
Additive pharmacodynamic effects (QT prolongation, serotonin reuptake inhibition, anticholinergic action) with competition for CYP2D6 and CYP2C19 metabolism.
What to do
Avoid concurrent use and consolidate to a single tricyclic. If a transition is needed, taper one before starting the other and monitor ECG.
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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Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide 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 Amitriptyline with Doxepin?
MediHelp rates the interaction as major. Amitriptyline and Doxepin 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 are tricyclic antidepressants, so combining them gives duplicate therapy with additive anticholinergic, sedative, cardiac conduction and QT effects. Serotonergic effects and overdose-type toxicity are also more likely.
How serious is the interaction between Amitriptyline and Doxepin?
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 concurrent use and consolidate to a single tricyclic. If a transition is needed, taper one before starting the other and monitor ECG.
What other medicines interact with Amitriptyline?
MediHelp also lists interactions of Amitriptyline with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Amitriptyline page.
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