}

Perphenazine

Antipsychotic

Drug Overview

Perphenazine, marketed under the brand name Trilafon, is a first-generation phenothiazine antipsychotic medication.

It is approved for the treatment of schizophrenia and other psychotic disorders, and it may also be used off-label for severe nausea and vomiting.

Perphenazine works by blocking dopamine D2 receptors in the brain, reducing excessive dopaminergic activity associated with psychotic symptoms.

Relevant Genes and Their Roles

The primary gene involved in perphenazine metabolism is CYP2D6, a member of the cytochrome P450 enzyme family responsible for converting many drugs into inactive forms.

Variants in CYP2D6 can alter enzyme activity: reduced-function alleles slow perphenazine breakdown, raising drug levels, while increased-function alleles accelerate clearance, potentially lowering efficacy.

Impact of Genetics on Drug Response

CYP2D6 genetic variants define metabolizer phenotypes—from poor to ultrarapid—that influence perphenazine plasma concentrations, therapeutic effect, and side effect risk. Poor metabolizers may experience higher exposure and more adverse reactions, while ultrarapid metabolizers may clear the drug rapidly, risking reduced efficacy.

Expected Clinical Effects of Genetic Variation

Genetic differences in CYP2D6 activity can lead to variations in drug levels and clinical outcomes as shown below.

Ultrarapid Metabolizer

  • Effect on drug levels: Lower plasma concentrations due to rapid clearance.
  • Clinical consequence: Potential reduced therapeutic efficacy.
  • Side effects: Fewer side effects; mild and infrequent.

Normal Metabolizer

  • Effect on drug levels: Expected plasma concentrations within the typical range.
  • Clinical consequence: Standard therapeutic effect.
  • Side effects: Typical side effect profile; moderate frequency.

Intermediate Metabolizer

  • Effect on drug levels: Moderately increased drug concentrations.
  • Clinical consequence: Slightly higher risk of side effects.
  • Side effects: Mild to moderate; may occur more often.

Poor Metabolizer

  • Effect on drug levels: Significantly higher plasma concentrations.
  • Clinical consequence: Increased risk of adverse reactions, such as extrapyramidal symptoms.
  • Side effects: More severe and common; may require dose adjustment.

Indeterminate / Not Available

  • Effect on drug levels: Unknown.
  • Clinical consequence: No specific guidance; follow standard dosing with monitoring.
  • Side effects: Not determined; monitor clinically.

Dosing Guidelines

The following dosing guidelines are based on the available FDA pharmacogenetic associations table for CYP2D6 and perphenazine.

CYP2D6 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Ultrarapid Metabolizer No specific FDA guidance; may have reduced exposure Initiate therapy with recommended starting dose
Normal Metabolizer Expected typical metabolism and response Initiate therapy with recommended starting dose
Intermediate Metabolizer No specific FDA guidance; slight risk of increased exposure Initiate therapy with recommended starting dose and monitor
Poor Metabolizer Higher systemic concentrations and increased adverse reaction risk Consider dose reduction and close monitoring
Indeterminate / Not available Unknown impact Initiate therapy with recommended starting dose

Alternative Treatment Options

The FDA table does not list alternative treatment options for perphenazine based on CYP2D6 genotype. Clinicians may consider other antipsychotics with established pharmacogenetic guidance where appropriate.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

Interested in learning more about how your genetics may affect your response to medication? Get started with Gene2Rx today.

I'm Interested