Drug interactions
Nortriptyline + Paroxetine
Severity: Major
Nortriptyline and Paroxetine: 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
Paroxetine strongly inhibits CYP2D6 and can markedly increase nortriptyline concentrations, leading to toxicity such as arrhythmia, anticholinergic effects and seizures. Both drugs also enhance serotonergic activity, adding serotonin syndrome risk.
What this interaction means in plain words
Nortriptyline and Paroxetine 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.
Nortriptyline belongs to Central Nervous System; Paroxetine belongs to Central Nervous System.
Why it happens
Paroxetine potently inhibits CYP2D6 metabolism of nortriptyline, and both drugs increase serotonin.
What to do
Avoid the combination or use a much lower nortriptyline dose guided by plasma levels and ECG. Monitor for serotonin 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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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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Frequently asked questions
Can I take Nortriptyline with Paroxetine?
MediHelp rates the interaction as major. Nortriptyline and Paroxetine 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. Paroxetine strongly inhibits CYP2D6 and can markedly increase nortriptyline concentrations, leading to toxicity such as arrhythmia, anticholinergic effects and seizures. Both drugs also enhance serotonergic activity, adding serotonin syndrome risk.
How serious is the interaction between Nortriptyline and Paroxetine?
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 or use a much lower nortriptyline dose guided by plasma levels and ECG. Monitor for serotonin 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.
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