Drug interactions
Clomipramine + Protriptyline
Severity: Major
Clomipramine and Protriptyline: 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 are tricyclic antidepressants, so combining them duplicates therapy and adds QT prolongation, anticholinergic burden, sedation and serotonergic effects. This raises the risk of arrhythmia, seizures and serotonin toxicity, particularly in overdose or at high doses.
What this interaction means in plain words
Clomipramine and Protriptyline 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.
Why it happens
Additive pharmacodynamic effects: cardiac conduction and repolarization effects, serotonin and norepinephrine reuptake inhibition, and anticholinergic activity; possible competition for CYP2D6 metabolism.
What to do
Avoid combining two tricyclics and use a single agent at an optimized dose. If overlap is unavoidable, obtain an ECG and monitor for serotonergic and anticholinergic toxicity.
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 Clomipramine
- Arsenic trioxide + Clomipramine Contraindicated
- Clomipramine + Dofetilide Contraindicated
- Clomipramine + Droperidol Contraindicated
- Clomipramine + Isocarboxazid Contraindicated
- Clomipramine + Methylene blue Contraindicated
- Clomipramine + Pentamidine Contraindicated
Frequently asked questions
Can I take Clomipramine with Protriptyline?
MediHelp rates the interaction as major. Clomipramine and Protriptyline 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 duplicates therapy and adds QT prolongation, anticholinergic burden, sedation and serotonergic effects. This raises the risk of arrhythmia, seizures and serotonin toxicity, particularly in overdose or at high doses.
How serious is the interaction between Clomipramine and Protriptyline?
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 and use a single agent at an optimized dose. If overlap is unavoidable, obtain an ECG and monitor for serotonergic and anticholinergic toxicity.
What other medicines interact with Clomipramine?
MediHelp also lists interactions of Clomipramine with, for example, Arsenic trioxide, Dofetilide, Droperidol. The full list is on the Clomipramine page.
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