Drug interactions
Amitriptyline + Venlafaxine
Severity: Major
Amitriptyline and Venlafaxine: 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 drugs increase serotonergic and noradrenergic activity, which can lead to serotonin syndrome. Venlafaxine may also modestly raise tricyclic levels, and the combination can increase blood pressure and heart rate and the risk of arrhythmia.
What this interaction means in plain words
Amitriptyline 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.
Amitriptyline belongs to Central Nervous System; Venlafaxine belongs to Central Nervous System.
Why it happens
Additive serotonin and norepinephrine reuptake inhibition, with weak CYP2D6 inhibition by venlafaxine.
What to do
Avoid if possible; if combined, use low doses with slow titration and monitor for serotonin toxicity, blood pressure and 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 Venlafaxine
- Isocarboxazid + Venlafaxine Contraindicated
- Methylene blue + Venlafaxine Contraindicated
- Phenelzine + Venlafaxine Contraindicated
- Procarbazine + Venlafaxine Contraindicated
- Rasagiline + Venlafaxine Contraindicated
- Safinamide + Venlafaxine Contraindicated
Frequently asked questions
Can I take Amitriptyline with Venlafaxine?
MediHelp rates the interaction as major. Amitriptyline 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. Both drugs increase serotonergic and noradrenergic activity, which can lead to serotonin syndrome. Venlafaxine may also modestly raise tricyclic levels, and the combination can increase blood pressure and heart rate and the risk of arrhythmia.
How serious is the interaction between Amitriptyline 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 if possible; if combined, use low doses with slow titration and monitor for serotonin toxicity, blood pressure and 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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