Drug interactions
Clozapine + Trimipramine
Severity: Major
Clozapine and Trimipramine: 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
Combining these agents increases sedation and anticholinergic effects, and both can prolong the QT interval and lower the seizure threshold. Clozapine may also raise tricyclic concentrations through CYP inhibition, and the combination raises the risk of arrhythmia, seizures and constipation or ileus.
What this interaction means in plain words
Clozapine and Trimipramine 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.
Clozapine belongs to Central Nervous System; Trimipramine belongs to Central Nervous System.
Why it happens
Additive CNS depressant, anticholinergic, QT-prolonging and seizure-threshold-lowering effects, with possible CYP2D6 competition.
What to do
Avoid the combination if possible; if it is used, obtain a baseline ECG and electrolytes and repeat the ECG after dose changes. Monitor for seizures, sedation, hypotension and bowel function.
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 Trimipramine
- Disopyramide + Trimipramine Contraindicated
- Dofetilide + Trimipramine Contraindicated
- Ibutilide + Trimipramine Contraindicated
- Isocarboxazid + Trimipramine Contraindicated
- Pentamidine + Trimipramine Contraindicated
- Phenelzine + Trimipramine Contraindicated
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 Trimipramine?
MediHelp rates the interaction as major. Clozapine and Trimipramine 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. Combining these agents increases sedation and anticholinergic effects, and both can prolong the QT interval and lower the seizure threshold. Clozapine may also raise tricyclic concentrations through CYP inhibition, and the combination raises the risk of arrhythmia, seizures and constipation or ileus.
How serious is the interaction between Clozapine and Trimipramine?
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 the combination if possible; if it is used, obtain a baseline ECG and electrolytes and repeat the ECG after dose changes. Monitor for seizures, sedation, hypotension and bowel function.
What other medicines interact with Trimipramine?
MediHelp also lists interactions of Trimipramine with, for example, Disopyramide, Dofetilide, Ibutilide. The full list is on the Trimipramine page.
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