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; possible increased risk of treatment failure.
Therapeutic Recommendation
- Given limited data available, consider initiating therapy with recommended starting dose with careful monitoring.
Normal – Ultra Rapid Metabolizer*
Clinical Implication
- Normal to increased CYP2D6 enzyme activity.
- Limited data available; possible increased risk of treatment failure.
Therapeutic Recommendation
- Given limited data available, consider initiating therapy with recommended starting dose with careful monitoring.
Normal Metabolizer*
Clinical Implication
- Normal CYP2D6 enzyme activity.
- Expected response.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Resources
Intermediate Metabolizer*
Clinical Implication
- Decreased CYP2D6 enzyme activity.
- Limited data available.
Therapeutic Recommendation
- Initiate therapy with recommended starting dose.
Poor Metabolizer
Clinical Implication
- No CYP2D6 enzyme activity.
- Increased risk of adverse effects (e.g., dizziness, GI dysfunction, sexual dysfunction).
Therapeutic Recommendation
- Initiate vortioxetine at 5 mg once daily or consider an alternative drug (click here for table of alternatives). The maximum recommend dose of vortioxetine is 10 mg/day.
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.
*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.