Drug interactions
Clozapine + Diphenoxylate-atropine
Severity: Major
Clozapine and Diphenoxylate-atropine: 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 has marked anticholinergic and sedative effects, and adding atropine and an opioid can increase the risk of severe constipation, ileus, urinary retention, tachycardia and sedation. Clozapine-induced gastrointestinal hypomotility can be serious and occasionally fatal.
What this interaction means in plain words
Clozapine and Diphenoxylate-atropine 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; Diphenoxylate-atropine belongs to Gastrointestinal Tract.
Why it happens
Additive antimuscarinic effects on the gut and bladder plus additive CNS depression.
What to do
Avoid routine use of antimotility agents with clozapine; if needed, use briefly and monitor bowel function, sedation and signs of ileus.
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 Diphenoxylate-atropine
- Diphenoxylate-atropine + Isocarboxazid Contraindicated
- Diphenoxylate-atropine + Phenelzine Contraindicated
- Diphenoxylate-atropine + Tranylcypromine Contraindicated
- Alfentanil + Diphenoxylate-atropine Major
- Alvimopan + Diphenoxylate-atropine Major
- Amitriptyline + Diphenoxylate-atropine 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 Diphenoxylate-atropine?
MediHelp rates the interaction as major. Clozapine and Diphenoxylate-atropine 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 has marked anticholinergic and sedative effects, and adding atropine and an opioid can increase the risk of severe constipation, ileus, urinary retention, tachycardia and sedation. Clozapine-induced gastrointestinal hypomotility can be serious and occasionally fatal.
How serious is the interaction between Clozapine and Diphenoxylate-atropine?
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 use of antimotility agents with clozapine; if needed, use briefly and monitor bowel function, sedation and signs of ileus.
What other medicines interact with Diphenoxylate-atropine?
MediHelp also lists interactions of Diphenoxylate-atropine with, for example, Isocarboxazid, Phenelzine, Tranylcypromine. The full list is on the Diphenoxylate-atropine page.
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