Drug interactions
Amitriptyline + Imipramine
Severity: Major
Amitriptyline and Imipramine: 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
Two tricyclic antidepressants give additive anticholinergic, sedative, cardiac conduction and serotonergic effects, and increase the risk of QT prolongation and arrhythmia. Therapeutic duplication offers no benefit and raises overdose-type toxicity.
What this interaction means in plain words
Amitriptyline and Imipramine 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; Imipramine belongs to Central Nervous System.
Why it happens
Additive sodium channel blockade, anticholinergic and monoamine reuptake effects, with competition for CYP2D6 and CYP2C19 metabolism.
What to do
Avoid combining two tricyclics. If a switch is required, cross-taper and consider an ECG and tricyclic levels.
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 Imipramine
- Dronedarone + Imipramine Contraindicated
- Imipramine + Isocarboxazid Contraindicated
- Imipramine + Phenelzine Contraindicated
- Imipramine + Pimozide Contraindicated
- Imipramine + Rasagiline Contraindicated
- Imipramine + Safinamide Contraindicated
Other interactions of Amitriptyline
- Amitriptyline + Isocarboxazid Contraindicated
- Amitriptyline + Methylene blue Contraindicated
- Amitriptyline + Phenelzine Contraindicated
- Amitriptyline + Pimozide Contraindicated
- Amitriptyline + Procarbazine Contraindicated
- Amitriptyline + Safinamide Contraindicated
Frequently asked questions
Can I take Amitriptyline with Imipramine?
MediHelp rates the interaction as major. Amitriptyline and Imipramine 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. Two tricyclic antidepressants give additive anticholinergic, sedative, cardiac conduction and serotonergic effects, and increase the risk of QT prolongation and arrhythmia. Therapeutic duplication offers no benefit and raises overdose-type toxicity.
How serious is the interaction between Amitriptyline and Imipramine?
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 two tricyclics. If a switch is required, cross-taper and consider an ECG and tricyclic levels.
What other medicines interact with Imipramine?
MediHelp also lists interactions of Imipramine with, for example, Dronedarone, Isocarboxazid, Phenelzine. The full list is on the Imipramine page.
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