To minimize the risk of severe side effects, the CPIC Dosing Guidelines for fluoropyrimidines recommend the use of an alternative drug for patients who are homozygous for DPYD SNPs associated with reduced DPD activity, and in heterozygous DPYD patients, the guidelines recommend considering a 50% reduction in the starting dose.
A 2014 publication reported that although rare in European populations, DPYD variants with reduced activity can be detected at appreciable frequencies in other populations, suggesting that testing in such populations would improve predictive genetic tests for fluoropyrimidine sensitivity.[PMID 24648345]
- With basically no activity (i.e. less than 12.5% of the normal wild-type activity):
- With little activity (12.5 - 25% of normal; "I560S-like")
- With reduced activity (but at least 25% of normal; "D949V-like")