Currently available guidelines for the implementation of pharmacogenetics recommend specific therapeutic guidelines for the following genotypes and allele combinations:

Intermediate DPYD Metabolizer: it is recommended to avoid the use of regimens with this drug and other analogues. If no other suitable therapeutic alternative is available, reduce the initial dose by 50% and adjust according to the plasma concentration or toxicity observed.

Poor DPYD Metabolizer:

In case of carrying two loss-of-function alleles (DPYD*2A or DPYD*13) avoid the use of regimens with this drug and other analogues. In case no other suitable therapeutic alternative is available, it is recommended to quantify the enzymatic activity of the DPD enzyme, and the initial dose should be adjusted accordingly. A patient with 0.5% of normal DPD activity would tolerate 0.8% of the standard dose (150 mg every 5 days). A patient with undetectable DPD activity would tolerate 0.43% of the standard dose (150 mg every 5 days with a third dose omitted).
In case of being a carrier of a loss-of-function allele and a partial activity allele (c. 2846 T>A) avoid the use of regimens with this drug and other analogues. In case no other suitable therapeutic alternative is available, it should be administered at a significantly reduced dose, <25% of the initial dose, with early therapeutic drug monitoring.

The guidelines also recommend confirming the metabolic status of the DPD enzyme by measuring enzyme activity before initiating fluoropyrimidine therapy.

Clinical Pharmacogenetics Implementation Consortium (CPIC)

Dutch Pharmacogenetics Working Group (DPWG)

French National Network of Pharmacogenetics (RNPGx)

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