Drug interactions
Clozapine + Epinephrine
Severity: Major
Clozapine and Epinephrine: 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
Clozapine blocks alpha-1 adrenergic receptors, which can blunt epinephrine's vasoconstrictor effect and leave beta-mediated vasodilation unopposed. This may cause marked hypotension and reflex tachycardia, reducing the benefit of epinephrine as a pressor.
What this interaction means in plain words
Clozapine and Epinephrine 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; Epinephrine belongs to Endocrine.
Why it happens
Alpha-1 adrenergic antagonism by clozapine causes epinephrine reversal.
What to do
Avoid epinephrine for treating clozapine-induced hypotension, and use a pure alpha agonist such as norepinephrine or phenylephrine instead. Use epinephrine for anaphylaxis as indicated, with close hemodynamic monitoring.
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 Clozapine
- Clozapine + Deferiprone Contraindicated
- Clozapine + Irinotecan Contraindicated
- Clozapine + Pimozide Contraindicated
- Clozapine + Thioridazine Contraindicated
- Acalabrutinib + Clozapine Major
- Adagrasib + Clozapine Major
Other interactions of Epinephrine
- Epinephrine + Isocarboxazid Contraindicated
- Epinephrine + Phenelzine Contraindicated
- Epinephrine + Tranylcypromine Contraindicated
- Acebutolol + Epinephrine Major
- Amitriptyline + Epinephrine Major
- Amoxapine + Epinephrine Major
Frequently asked questions
Can I take Clozapine with Epinephrine?
MediHelp rates the interaction as major. Clozapine and Epinephrine 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 blocks alpha-1 adrenergic receptors, which can blunt epinephrine's vasoconstrictor effect and leave beta-mediated vasodilation unopposed. This may cause marked hypotension and reflex tachycardia, reducing the benefit of epinephrine as a pressor.
How serious is the interaction between Clozapine and Epinephrine?
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 epinephrine for treating clozapine-induced hypotension, and use a pure alpha agonist such as norepinephrine or phenylephrine instead. Use epinephrine for anaphylaxis as indicated, with close hemodynamic monitoring.
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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