Drug interactions
Clozapine + Protriptyline
Severity: Major
Clozapine and Protriptyline: major interaction.
Last updated Sources: UK SmPC
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 have anticholinergic, sedative and QT-prolonging properties, and tricyclics can also lower the seizure threshold, as can clozapine. Combined use increases risks of arrhythmia, seizures and anticholinergic toxicity.
What this interaction means in plain words
Clozapine 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 QT prolongation, anticholinergic effects, CNS depression and seizure threshold lowering.
What to do
Obtain an ECG and electrolytes at baseline and during therapy, and monitor for seizures, constipation and sedation. Consider an alternative antidepressant with less anticholinergic and cardiac liability.
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
- Clozapine Viatris 100 mg Orodispersible Tablets - SmPC sections 4.3/4.5 (class statement: tricyclic antidepressants; "With tricyclic antidepressants, phenothiazines and type 1C anti-arrhythmics, which are known to bind to cytochrome P450 2D6, no clinically relevant interactions") — electronic medicines compendium (UK SmPC)
Other interactions of Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Frequently asked questions
Can I take Clozapine with Protriptyline?
MediHelp rates the interaction as major. Clozapine 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 drugs have anticholinergic, sedative and QT-prolonging properties, and tricyclics can also lower the seizure threshold, as can clozapine. Combined use increases risks of arrhythmia, seizures and anticholinergic toxicity.
How serious is the interaction between Clozapine 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: Obtain an ECG and electrolytes at baseline and during therapy, and monitor for seizures, constipation and sedation. Consider an alternative antidepressant with less anticholinergic and cardiac liability.
What other medicines interact with Clozapine?
MediHelp also lists interactions of Clozapine with, for example, Deferiprone, Irinotecan, Pimozide. The full list is on the Clozapine page.
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