The FDA has updated the product labeling of capecitabine (Xeloda, Genentech) and fluorouracil to reflect the risks of acute toxicity and potentially fatal adverse reactions in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.

“All healthcare providers should be aware of the risks of DPD deficiency, inform patients prior to treatment about the potential for serious and life-threatening toxicities due to DPD deficiency, and test patients for genetic variants of DPYD prior to initiating treatment with capecitabine or [fluorouracil] unless immediate treatment is necessary,” according to a new FDA safety announcement.

The DYPD gene encodes the enzyme DPD, which breaks down more than 80% of fluorouracil. Certain variants in the gene are known to cause DPD deficiency, and affected patients with partial or complete DPD deficiency may experience early-onset toxicity, including life-threatening mucositis, diarrhea, neutropenia, and neurotoxicity when exposed to capecitabine and fluorouracil, the FDA explained.

Recent labeling changes to both drugs include a boxed warning highlighting these risks, recommending DPYD testing prior to treatment when possible, and recommending against treatment in those with homozygous or compound heterozygous DYPD variants that result in complete DPD deficiency.

A n ew subsection was also added to dosage and administration information for each drug, addressing the need for evaluation and testing for DPD deficiency prior to treatment initiation and for individualized dosing in those with partial DPD deficiency. The warnings and precautions sections were similarly updated.

In January 2025, the FDA shared a related announcement highlighting initial label changes and underscoring the need for discussions with patients about these risks. The new announcement provides information about the latest labeling changes.

“The FDA will continue to monitor this safety issue and evaluate the evolving landscape and impact of DPD deficiency on the safety of capecitabine and fluorouracil; additional regulatory actions may be considered,” according to the latest announcement, which “urges patients and healthcare providers to report side effects to the FDA MedWatch program.” 

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.