Drug interactions
Dextromethorphan + Perphenazine
Severity: Moderate
Dextromethorphan and Perphenazine: moderate 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
Perphenazine is a CYP2D6 substrate and a strong inhibitor of this enzyme, so dextromethorphan concentrations may increase. Dextromethorphan's serotonergic activity also gives a theoretical risk of serotonin toxicity or neuroleptic malignant syndrome.
What this interaction means in plain words
Dextromethorphan and Perphenazine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Dextromethorphan belongs to Respiratory; Perphenazine belongs to Central Nervous System.
Why it happens
Perphenazine inhibits CYP2D6, reducing dextromethorphan clearance, with possible additive serotonergic effects.
What to do
Monitor for dizziness, sedation and confusion, and keep dextromethorphan doses low. Check for fever, rigidity or autonomic instability if the patient becomes acutely unwell.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Dextromethorphan
- Dextromethorphan + Isocarboxazid Contraindicated
- Dextromethorphan + Linezolid Contraindicated
- Dextromethorphan + Phenelzine Contraindicated
- Dextromethorphan + Rasagiline Contraindicated
- Dextromethorphan + Safinamide Contraindicated
- Dextromethorphan + 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 Dextromethorphan with Perphenazine?
MediHelp rates the interaction as moderate. Dextromethorphan and Perphenazine can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Perphenazine is a CYP2D6 substrate and a strong inhibitor of this enzyme, so dextromethorphan concentrations may increase. Dextromethorphan's serotonergic activity also gives a theoretical risk of serotonin toxicity or neuroleptic malignant syndrome.
How serious is the interaction between Dextromethorphan and Perphenazine?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor for dizziness, sedation and confusion, and keep dextromethorphan doses low. Check for fever, rigidity or autonomic instability if the patient becomes acutely unwell.
What other medicines interact with Dextromethorphan?
MediHelp also lists interactions of Dextromethorphan with, for example, Isocarboxazid, Linezolid, Phenelzine. The full list is on the Dextromethorphan page.
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