Drug interactions
Protriptyline + Trazodone
Severity: Major
Protriptyline and Trazodone: 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
Both drugs increase serotonergic tone and can prolong the QT interval. Combined use raises the risk of serotonin syndrome, arrhythmia, and additive sedation, hypotension and anticholinergic effects. Trazodone may also raise tricyclic concentrations via CYP2D6 competition.
What this interaction means in plain words
Protriptyline and Trazodone 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.
Why it happens
Additive serotonin reuptake inhibition and QTc prolongation, with possible pharmacokinetic increase in tricyclic levels.
What to do
Avoid the combination when possible. If used, start low, obtain an ECG and monitor for serotonin toxicity and tricyclic adverse effects.
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 Trazodone
- Arsenic trioxide + Trazodone Contraindicated
- Ibutilide + Trazodone Contraindicated
- Isocarboxazid + Trazodone Contraindicated
- Levoketoconazole + Trazodone Contraindicated
- Methylene blue + Trazodone Contraindicated
- Phenelzine + Trazodone Contraindicated
Frequently asked questions
Can I take Protriptyline with Trazodone?
MediHelp rates the interaction as major. Protriptyline and Trazodone 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 increase serotonergic tone and can prolong the QT interval. Combined use raises the risk of serotonin syndrome, arrhythmia, and additive sedation, hypotension and anticholinergic effects. Trazodone may also raise tricyclic concentrations via CYP2D6 competition.
How serious is the interaction between Protriptyline and Trazodone?
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 when possible. If used, start low, obtain an ECG and monitor for serotonin toxicity and tricyclic adverse effects.
What other medicines interact with Trazodone?
MediHelp also lists interactions of Trazodone with, for example, Arsenic trioxide, Ibutilide, Isocarboxazid. The full list is on the Trazodone page.
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