Drug interactions
Clozapine + Perphenazine
Severity: Major
Clozapine and Perphenazine: 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
Combining two antipsychotics increases the risk of sedation, QT prolongation, extrapyramidal symptoms and neuroleptic malignant syndrome. Clozapine also adds anticholinergic, hypotensive and seizure risks, and perphenazine may raise clozapine levels via CYP2D6 inhibition.
What this interaction means in plain words
Clozapine and Perphenazine 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; Perphenazine belongs to Central Nervous System.
Why it happens
Additive dopamine D2 blockade, CNS depression and QT prolongation, with possible CYP2D6 inhibition by perphenazine.
What to do
Use only when clearly justified, with ECG and electrolyte monitoring and surveillance for sedation, hypotension and movement disorders. Consider clozapine level monitoring and dose reduction if adverse effects occur.
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 Perphenazine
- Ibutilide + Perphenazine Contraindicated
- Perphenazine + Pimozide Contraindicated
- Perphenazine + Thioridazine Contraindicated
- Adagrasib + Perphenazine Major
- Alfentanil + Perphenazine Major
- Amiodarone + Perphenazine Major
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 Perphenazine?
MediHelp rates the interaction as major. Clozapine and Perphenazine 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 two antipsychotics increases the risk of sedation, QT prolongation, extrapyramidal symptoms and neuroleptic malignant syndrome. Clozapine also adds anticholinergic, hypotensive and seizure risks, and perphenazine may raise clozapine levels via CYP2D6 inhibition.
How serious is the interaction between Clozapine and Perphenazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use only when clearly justified, with ECG and electrolyte monitoring and surveillance for sedation, hypotension and movement disorders. Consider clozapine level monitoring and dose reduction if adverse effects occur.
What other medicines interact with Perphenazine?
MediHelp also lists interactions of Perphenazine with, for example, Ibutilide, Pimozide, Thioridazine. The full list is on the Perphenazine page.
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