Drug interactions
Perphenazine + Risperidone
Severity: Major
Perphenazine and Risperidone: 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
Both agents are D2 antagonists so combining them raises the risk of extrapyramidal symptoms and neuroleptic malignant syndrome. QT prolongation and sedation are additive. Perphenazine also inhibits CYP2D6 and can raise risperidone exposure.
What this interaction means in plain words
Perphenazine and Risperidone 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.
Perphenazine belongs to Central Nervous System; Risperidone belongs to Central Nervous System.
Why it happens
Additive D2 blockade and QT effects, with perphenazine CYP2D6 inhibition increasing risperidone levels.
What to do
Avoid the combination if possible; if used, lower the risperidone dose and monitor for parkinsonism, sedation and QTc. Check electrolytes and ECG at baseline.
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 Perphenazine
- Ibutilide + Perphenazine Contraindicated
- Perphenazine + Pimozide Contraindicated
- Perphenazine + Thioridazine Contraindicated
- Adagrasib + Perphenazine Major
- Alfentanil + Perphenazine Major
- Amiodarone + Perphenazine Major
Other interactions of Risperidone
- Ibutilide + Risperidone Contraindicated
- Risperidone + Vandetanib Contraindicated
- Adagrasib + Risperidone Major
- Amiodarone + Risperidone Major
- Amisulpride + Risperidone Major
- Amoxapine + Risperidone Major
Frequently asked questions
Can I take Perphenazine with Risperidone?
MediHelp rates the interaction as major. Perphenazine and Risperidone 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 are D2 antagonists so combining them raises the risk of extrapyramidal symptoms and neuroleptic malignant syndrome. QT prolongation and sedation are additive. Perphenazine also inhibits CYP2D6 and can raise risperidone exposure.
How serious is the interaction between Perphenazine and Risperidone?
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 if possible; if used, lower the risperidone dose and monitor for parkinsonism, sedation and QTc. Check electrolytes and ECG at baseline.
What other medicines interact with Perphenazine?
MediHelp also lists interactions of Perphenazine with, for example, Ibutilide, Pimozide, Thioridazine. The full list is on the Perphenazine page.
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