Intermediate Metabolizer with an enzyme Activity Score of 1.5
Clinical Implication
Decreased DPD enzyme activity.
Increased risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).
Therapeutic Recommendation
Reduce starting dose by 50%, thereafter titrate dose based on toxicity tolerance or therapeutic drug monitoring.
Intermediate Metabolizer with an enzyme Activity Score of 1
Clinical Implication
Decreased DPD enzyme activity.
Increased risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).
Therapeutic Recommendation
Reduce starting dose by 25 to 50%, thereafter titrate dose based on toxicity tolerance or therapeutic drug monitoring.
Poor Metabolizer with an enzyme Activity Score of 0.5
Clinical Implication
Little to no DPD enzyme activity.
Very high risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).
Therapeutic Recommendation
Avoid fluoropyrimidines and use alternative agent. If alternatives are not appropriate and phenotype testing is unavailable to estimate starting dose, may consider an initial dose reduction of 75% and utilize therapeutic drug monitoring.
Poor Metabolizer with an enzyme Activity Score of 0
Clinical Implication
Little to no DPD enzyme activity.
Very high risk for severe or even fatal drug toxicity (e.g. neutropenia, diarrhea, stomatitis, mucositis, hand-foot syndrome).
Therapeutic Recommendation
Avoid fluoropyrimidines and use alternative agent.
Unable to Genotype or Assay Failure
The analysis failed to yield an informative result and thus no genotype is reported.
Reference
Amstutz U et al. Clin Pharmacol Ther. 2018 Feb;103(2):210-216. PMID: 29152729.