Strong and moderate inhibitors of CYP2D6 (bupropion, fluoxetine, paroxetine, quinidine, terbinafine, cinacalcet, duloxetine, mirabegron, abiraterone, and lorcaserin) can lead to phenoconversion. If a patient is taking one or more of the above listed medications (and that medication will not be discontinued prior to starting the new medication of interest), use the CYP2D6 Phenoconversion Calculator to determine the clinical phenotype and use that phenotype in the list below.
Ultra Rapid Metabolizer
Clinical Implication
- Increased CYP2D6 enzyme activity.
- Limited data available.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Normal – Ultra Rapid Metabolizer*
Clinical Implication
- Normal to increased CYP2D6 enzyme activity.
- Limited data available.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Normal Metabolizer*
Clinical Implication
- Normal CYP2D6 enzyme activity.
- Normal response expected.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Intermediate Metabolizer*
Clinical Implication
- Decreased CYP2D6 enzyme activity.
- Limited data available.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Resources
Poor Metabolizer
Clinical Implication
- No CYP2D6 enzyme activity.
- Increased risk of adverse effects (e.g., insomnia, GI dysfunction, sexual dysfunction, hyperhidrosis, increased blood pressure and heart rate) and possibly treatment failure.
Therapeutic Recommendation
- Avoid venlafaxine and consider an alternative drug (click here for table of alternatives).
Unable to Genotype or Assay Failure
- The analysis failed to yield an informative result and thus no genotype is reported.
Unknown Phenotype
- This individual is carrying at least one allele with uncertain/unknown function and the predicted phenotype cannot be determined at this time.
Reference: Review a Table of Pharmacogenetic associations. U.S. Food and Drug Administration
*Some laboratories have started calling activity scores of 1.0 as Intermediate Metabolizers, however they are still classified as Normal Metabolizers with UF Health Pathology.