Drug interactions
Clozapine + Propafenone
Severity: Major
Clozapine and Propafenone: 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 drugs can affect cardiac conduction and repolarization, and clozapine also carries risks of myocarditis, tachycardia and orthostasis. Propafenone inhibits CYP2D6, which can modestly increase clozapine levels, adding to toxicity risk.
What this interaction means in plain words
Clozapine and Propafenone 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; Propafenone belongs to Cardiovascular.
Why it happens
Additive pharmacodynamic QT and conduction effects, with CYP2D6 inhibition by propafenone increasing clozapine exposure.
What to do
Avoid if an alternative antiarrhythmic is feasible. If combined, obtain a baseline and follow-up ECG, monitor for clozapine toxicity, and consider checking clozapine 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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References
Other interactions of Propafenone
- Dofetilide + Propafenone Contraindicated
- Dronedarone + Propafenone Contraindicated
- Nilotinib + Propafenone Contraindicated
- Nirmatrelvir / ritonavir + Propafenone Contraindicated
- Nirmatrelvir + Propafenone Contraindicated
- Pimozide + Propafenone 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 Propafenone?
MediHelp rates the interaction as major. Clozapine and Propafenone 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 can affect cardiac conduction and repolarization, and clozapine also carries risks of myocarditis, tachycardia and orthostasis. Propafenone inhibits CYP2D6, which can modestly increase clozapine levels, adding to toxicity risk.
How serious is the interaction between Clozapine and Propafenone?
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 an alternative antiarrhythmic is feasible. If combined, obtain a baseline and follow-up ECG, monitor for clozapine toxicity, and consider checking clozapine levels.
What other medicines interact with Propafenone?
MediHelp also lists interactions of Propafenone with, for example, Dofetilide, Dronedarone, Nilotinib. The full list is on the Propafenone page.
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