Drug interactions
Clozapine + Nortriptyline
Severity: Major
Clozapine and Nortriptyline: major interaction.
Last updated
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 cause sedation and anticholinergic effects, and each can prolong the QT interval or lower the seizure threshold. Tricyclics may also raise clozapine levels by inhibiting its metabolism. The combination may cause serious constipation, delirium, arrhythmia or seizures.
What this interaction means in plain words
Clozapine and Nortriptyline 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; Nortriptyline belongs to Central Nervous System.
Why it happens
Additive CNS depression, anticholinergic, QT and seizure-threshold effects, with possible CYP-mediated increase in clozapine exposure.
What to do
Monitor ECG, bowel function, sedation and seizure activity, and consider clozapine level monitoring. Use the lowest effective doses and watch for 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?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Clozapine and Nortriptyline, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
Other interactions of Nortriptyline
- Disopyramide + Nortriptyline Contraindicated
- Dofetilide + Nortriptyline Contraindicated
- Dronedarone + Nortriptyline Contraindicated
- Ibutilide + Nortriptyline Contraindicated
- Isocarboxazid + Nortriptyline Contraindicated
- Methylene blue + Nortriptyline Contraindicated
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 Nortriptyline?
MediHelp rates the interaction as major. Clozapine and Nortriptyline 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 cause sedation and anticholinergic effects, and each can prolong the QT interval or lower the seizure threshold. Tricyclics may also raise clozapine levels by inhibiting its metabolism. The combination may cause serious constipation, delirium, arrhythmia or seizures.
How serious is the interaction between Clozapine and Nortriptyline?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor ECG, bowel function, sedation and seizure activity, and consider clozapine level monitoring. Use the lowest effective doses and watch for clozapine toxicity.
What other medicines interact with Nortriptyline?
MediHelp also lists interactions of Nortriptyline with, for example, Disopyramide, Dofetilide, Dronedarone. The full list is on the Nortriptyline page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
