Drug interactions
Clozapine + Doxepin
Severity: Major
Clozapine and Doxepin: 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
Both drugs are sedating and anticholinergic, and each can prolong the QT interval. Combined use raises the risk of excessive sedation, constipation or ileus, orthostatic hypotension, seizures and ventricular arrhythmia. Doxepin may also modestly raise clozapine levels through CYP2D6 competition.
What this interaction means in plain words
Clozapine and Doxepin 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; Doxepin belongs to Dermatology.
Why it happens
Additive CNS depression, anticholinergic burden, seizure threshold lowering and QT prolongation, plus possible CYP2D6 inhibition.
What to do
Avoid the combination where possible; if needed, use the lowest effective doses, obtain a baseline ECG and correct potassium and magnesium. Monitor for sedation, bowel function, hypotension and clozapine toxicity.
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
- Clozapine Viatris 100 mg Orodispersible Tablets - SmPC sections 4.3/4.5 (class statement: tricyclic antidepressants; "With tricyclic antidepressants, phenothiazines and type 1C anti-arrhythmics, which are known to bind to cytochrome P450 2D6, no clinically relevant interactions") — electronic medicines compendium (UK SmPC)
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 Doxepin
- Doxepin + Isocarboxazid Contraindicated
- Doxepin + Phenelzine Contraindicated
- Doxepin + Procarbazine Contraindicated
- Doxepin + Safinamide Contraindicated
- Doxepin + Selegiline Contraindicated
- Doxepin + Tranylcypromine Contraindicated
Frequently asked questions
Can I take Clozapine with Doxepin?
MediHelp rates the interaction as major. Clozapine and Doxepin 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 anticholinergic, and each can prolong the QT interval. Combined use raises the risk of excessive sedation, constipation or ileus, orthostatic hypotension, seizures and ventricular arrhythmia. Doxepin may also modestly raise clozapine levels through CYP2D6 competition.
How serious is the interaction between Clozapine and Doxepin?
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 the combination where possible; if needed, use the lowest effective doses, obtain a baseline ECG and correct potassium and magnesium. Monitor for sedation, bowel function, hypotension and clozapine toxicity.
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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