Drug interactions
Paroxetine + Perphenazine
Severity: Major
Paroxetine and Perphenazine: 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, which clears perphenazine, producing several-fold higher perphenazine levels and more extrapyramidal symptoms and sedation. Both drugs are CYP2D6 substrates and perphenazine may also affect paroxetine metabolism.
What this interaction means in plain words
Paroxetine and Perphenazine 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 belongs to Central Nervous System; Perphenazine belongs to Central Nervous System.
Why it happens
CYP2D6 inhibition by paroxetine markedly reducing perphenazine clearance, with possible additive QTc effects.
What to do
Use lower perphenazine doses, typically starting at about half the usual dose, and monitor for extrapyramidal symptoms, sedation, and QTc. Adjust the dose when paroxetine is started or stopped.
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 Paroxetine
- Isocarboxazid + Paroxetine Contraindicated
- Methylene blue + Paroxetine Contraindicated
- Paroxetine + Phenelzine Contraindicated
- Paroxetine + Pimozide Contraindicated
- Paroxetine + Procarbazine Contraindicated
- Paroxetine + Selegiline Contraindicated
Other interactions of Perphenazine
- Ibutilide + Perphenazine Contraindicated
- Perphenazine + Pimozide Contraindicated
- Perphenazine + Thioridazine Contraindicated
- Adagrasib + Perphenazine Major
- Alfentanil + Perphenazine Major
- Amiodarone + Perphenazine Major
Frequently asked questions
Can I take Paroxetine with Perphenazine?
MediHelp rates the interaction as major. Paroxetine and Perphenazine 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, which clears perphenazine, producing several-fold higher perphenazine levels and more extrapyramidal symptoms and sedation. Both drugs are CYP2D6 substrates and perphenazine may also affect paroxetine metabolism.
How serious is the interaction between Paroxetine and Perphenazine?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Use lower perphenazine doses, typically starting at about half the usual dose, and monitor for extrapyramidal symptoms, sedation, and QTc. Adjust the dose when paroxetine is started or stopped.
What other medicines interact with Paroxetine?
MediHelp also lists interactions of Paroxetine with, for example, Isocarboxazid, Methylene blue, Phenelzine. The full list is on the Paroxetine page.
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