Drug interactions
Fluoxetine + Nortriptyline
Severity: Major
Fluoxetine and Nortriptyline: major interaction.
Last updated Sources: US FDA label
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
Fluoxetine and its long-acting metabolite strongly inhibit the enzyme that clears nortriptyline, so tricyclic concentrations can rise substantially. This may cause anticholinergic effects, cardiac conduction disturbances and arrhythmia, and seizures. Additive serotonergic activity also raises the risk of serotonin syndrome.
What this interaction means in plain words
Fluoxetine 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.
Fluoxetine belongs to Central Nervous System; Nortriptyline belongs to Central Nervous System.
Why it happens
Fluoxetine and norfluoxetine inhibit CYP2D6-mediated nortriptyline metabolism, and both drugs increase synaptic serotonin.
What to do
Start with a low nortriptyline dose and titrate using plasma concentrations and ECG monitoring, or choose an alternative antidepressant. Remember that CYP2D6 inhibition persists for weeks after fluoxetine is stopped, and watch 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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References
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 Fluoxetine
- Fluoxetine + Isocarboxazid Contraindicated
- Fluoxetine + Mavacamten Contraindicated
- Fluoxetine + Methylene blue Contraindicated
- Fluoxetine + Phenelzine Contraindicated
- Fluoxetine + Pimozide Contraindicated
- Fluoxetine + Rasagiline Contraindicated
Frequently asked questions
Can I take Fluoxetine with Nortriptyline?
MediHelp rates the interaction as major. Fluoxetine 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. Fluoxetine and its long-acting metabolite strongly inhibit the enzyme that clears nortriptyline, so tricyclic concentrations can rise substantially. This may cause anticholinergic effects, cardiac conduction disturbances and arrhythmia, and seizures. Additive serotonergic activity also raises the risk of serotonin syndrome.
How serious is the interaction between Fluoxetine 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: Start with a low nortriptyline dose and titrate using plasma concentrations and ECG monitoring, or choose an alternative antidepressant. Remember that CYP2D6 inhibition persists for weeks after fluoxetine is stopped, and watch 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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