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The U.S. Food and Drug Administration (FDA) initiated this study in the Sentinel System to better understand genetic testing patterns for dihydropyrimidine dehydrogenase (DPYD) gene variants among patients treated with fluoropyrimidines in the United States.
The enzyme dihydropyrimidine dehydrogenase, encoded by the DPYD gene, plays an important role in the breakdown of fluoropyrimidines. Fluoropyrimidines are widely used for the treatment of solid tumors. Individuals with certain homozygous or compound heterozygous variants of the DPYD gene have reduced enzyme activity and are at increased risk for acute early-onset toxicity and serious adverse reactions. Warnings related to DPD deficiency for fluoropyrimidine products were incrementally strengthened through multiple labeling updates since 2015. Most recently, the labeling for Xeloda (capecitabine) and fluorouracil products was updated in October 2025 and February 2026, respectively, to recommend DPYD testing before fluoropyrimidine administration. FDA used the Sentinel Distributed Database to assess the frequency of DPYD gene testing among insured patients initiating fluoropyrimidine treatment in the United States, in the period before the most recent updated product labeling.
The results indicated DPYD testing is infrequent among insured patients receiving fluoropyrimidine treatment. During the study period, January 1, 2018, to May 31, 2025, DPYD testing (i.e., testing within ± 60 days of treatment initiation) was performed in 0.4% of patients who received any fluoropyrimidine overall, in 0.3% of patients who received testing in the 60 days before initiating any fluoropyrimidine treatment, and in 0.2% of patients who received DPYD testing within 60 days after initiating treatment for any fluoropyrimidine.
The results helped FDA to understand DPYD testing patterns before and after fluoropyrimidine administration. Recent revisions to fluoropyrimidine product labeling included recommendations to test patients for DPYD variants before treatment. These results will allow FDA to assess whether and how testing patterns shift in response to those labeling changes.