Drug interactions
Desvenlafaxine + Protriptyline
Severity: Major
Desvenlafaxine and Protriptyline: 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 agents inhibit monoamine reuptake, so combining them raises the risk of serotonin syndrome, and the tricyclic adds anticholinergic and cardiac effects. Desvenlafaxine may also modestly raise tricyclic levels through CYP2D6 inhibition at higher doses.
What this interaction means in plain words
Desvenlafaxine and Protriptyline 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 serotonergic and noradrenergic reuptake inhibition, with possible weak CYP2D6 inhibition by desvenlafaxine.
What to do
Avoid combining where possible; if necessary, use low protriptyline doses and monitor ECG, blood pressure and serotonin toxicity signs. Consider protriptyline levels if toxicity is suspected.
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 Desvenlafaxine
- Desvenlafaxine + Isocarboxazid Contraindicated
- Desvenlafaxine + Methylene blue Contraindicated
- Desvenlafaxine + Phenelzine Contraindicated
- Desvenlafaxine + Rasagiline Contraindicated
- Desvenlafaxine + Safinamide Contraindicated
- Desvenlafaxine + Selegiline Contraindicated
Frequently asked questions
Can I take Desvenlafaxine with Protriptyline?
MediHelp rates the interaction as major. Desvenlafaxine and Protriptyline 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 agents inhibit monoamine reuptake, so combining them raises the risk of serotonin syndrome, and the tricyclic adds anticholinergic and cardiac effects. Desvenlafaxine may also modestly raise tricyclic levels through CYP2D6 inhibition at higher doses.
How serious is the interaction between Desvenlafaxine and Protriptyline?
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 combining where possible; if necessary, use low protriptyline doses and monitor ECG, blood pressure and serotonin toxicity signs. Consider protriptyline levels if toxicity is suspected.
What other medicines interact with Desvenlafaxine?
MediHelp also lists interactions of Desvenlafaxine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Desvenlafaxine page.
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