Drug interactions
Clozapine + Promethazine
Severity: Major
Clozapine and Promethazine: major interaction.
Last updated Sources: Base de donnees publique des medicaments (France)
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 are sedating and have anticholinergic and antidopaminergic effects, so combined use increases drowsiness, constipation, hypotension and possibly extrapyramidal symptoms. Clozapine-related constipation can progress to serious bowel obstruction when anticholinergic load is increased, and clozapine also carries respiratory and cardiovascular risks with other CNS depressants.
What this interaction means in plain words
Clozapine and Promethazine 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; Promethazine belongs to Respiratory.
Why it happens
Additive muscarinic, histaminic and dopaminergic receptor blockade with additive CNS depression.
What to do
Avoid routine co-prescription where an alternative exists; if used, monitor sedation, blood pressure and bowel function and reduce doses as needed. Watch for signs of neuroleptic malignant syndrome.
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 Promethazine
- Cabergoline + Promethazine Contraindicated
- Dopamine + Promethazine Contraindicated
- Ibutilide + Promethazine Contraindicated
- Pimozide + Promethazine Contraindicated
- Promethazine + Thioridazine Contraindicated
- Alfentanil + Promethazine 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 Promethazine?
MediHelp rates the interaction as major. Clozapine and Promethazine 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 are sedating and have anticholinergic and antidopaminergic effects, so combined use increases drowsiness, constipation, hypotension and possibly extrapyramidal symptoms. Clozapine-related constipation can progress to serious bowel obstruction when anticholinergic load is increased, and clozapine also carries respiratory and cardiovascular risks with other CNS depressants.
How serious is the interaction between Clozapine and Promethazine?
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 routine co-prescription where an alternative exists; if used, monitor sedation, blood pressure and bowel function and reduce doses as needed. Watch for signs of neuroleptic malignant syndrome.
What other medicines interact with Promethazine?
MediHelp also lists interactions of Promethazine with, for example, Cabergoline, Dopamine, Ibutilide. The full list is on the Promethazine page.
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