Table 4.

Dosing of fluoropyrimidines according to DPD phenotype based on genotype

Phenotype	Genotype	Implications	Dosing recommendation
Normal metabolizer (Activity score 2)	Wild-type (absence of mutation)	Normal DPD activity and normal risk for fluoropyrimidine toxicity	According to the data sheet
Intermediate metabolizer (activity score 1–1.5)	Wild-type allele and mutated allele (*2A o *13 or c.2846A>T or HapB3)	Decreased DPD activity (30–70%) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidines	Reduce starting dose by 50% followed by titration of dose based on toxicity or pharmacokinetics
	Two mutated alleles (c.2846A>T or HapB3)
Poor metabolizer (Activity score 0–0.5)	Two mutated alleles (*2A or *13)	Complete or almost complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidines	Contraindicated treatment with fluoropyrimidines; look for alternative agents*
	One mutated allele (*2A or *13) and one mutated allele (c.2846A>T or HapB3)

5-FU 5-fluorouracil, CPIC Clinical Pharmacogenetics Implementation Consortium, DPD dihydropyrimidine dehydrogenase

*In the event that alternative agents are not considered a suitable therapeutic option and patient has an activity score of 0,5, CPIC indicates that 5-FU could be administered at a strongly reduced dose (< 25% of the normal dose) with early therapeutic drug monitoring of plasma concentration of 5-FU, to discontinue therapy if the drug level is too high [1]