Table 10:

Genotype Determination and Treatment Adjustments

DPYD Genotype	Gene Activity Score	Likely Phenotype	Treatment Adjustment
Wild-type or noncarrier: • 2 normal-function variants	2	Normal metabolizer; normal DPD enzyme activity with “normal” risk for fluoropyrimidine toxicity	No dose adjustments; use label-recommended dose
DPYD variant carrier: • 1 normal-function variant and 1 no-function variant • 1 normal-function variant and 1 decreased-function variant • 2 decreased-function variants	1 or 1.5	Intermediate metabolizer; reduced DPD enzyme activity and increased risk for severe or fatal toxicity when treated with fluoropyrimidine drugs	Reduced dose followed by titration of dose based on occurrence of toxicity
DPYD variant carrier: • 2 no-function variant • 1 no-function variant and 1 decreased-function variant	0 or 0.5	Poor metabolizer; complete DPD deficiency and high risk for severe or fatal toxicity when treated with fluoropyrimidine drugs	Alternative chemotherapy regimen

Abbreviation: DPD, dihydropyrimidine dehydrogenase.

Source: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline, 2017.⁸