FDA updates labeling for capecitabine and 5-FU to strengthen safety guidance on DPD deficiency, DPYD testing, and individualized dosing
Written By: Pharmacally Medical News Desk
The U.S. Food and Drug Administration has updated the prescribing information for capecitabine (Xeloda) and fluorouracil (5-FU) to better address the risk of severe toxicity in patients with dihydropyrimidine dehydrogenase (DPD) deficiency. The revisions are aimed at improving early risk identification and supporting safer treatment decisions.
What led to the labeling update
Capecitabine and fluorouracil are cornerstone fluoropyrimidine therapies in oncology. Their breakdown in the body depends largely on the DPD enzyme, which is produced based on instructions from the DPYD gene. When DPD activity is significantly reduced or absent due to certain genetic variants, these drugs can accumulate to dangerous levels.
Patients with complete DPD deficiency are particularly vulnerable to rapid-onset and severe adverse effects, including gastrointestinal toxicity, bone marrow suppression, neurological complications, and death. Even patients with partial enzyme activity may experience heightened toxicity compared with the general population.
Summary of the revised labeling
Boxed Warning
The updated Boxed Warning places stronger emphasis on the risk of serious or fatal reactions in patients with complete DPD deficiency. It now points clinicians toward DPYD genetic testing before treatment begins, when feasible, and advises against using capecitabine or 5-FU in patients with specific DPYD variant patterns linked to complete enzyme deficiency.
Dosage and Administration
A new Section 2.1, focused on evaluating DPD status before starting therapy, has been added. This section directs clinicians to avoid these agents in patients known to have DPYD variants associated with complete DPD deficiency. For those with partial deficiency, dosing decisions should be tailored to the individual rather than following standard regimens.
Warnings and Precautions
The Warnings and Precautions section reinforces the importance of assessing DPYD genetic status prior to initiating treatment, except in situations where delaying therapy is not clinically appropriate.
The revised language signals a more proactive approach to preventing fluoropyrimidine-related harm. Clinicians are encouraged to discuss genetic risk with patients, consider pre-treatment testing, and remain alert to early signs of toxicity. Individualized dosing and close monitoring become especially important when partial DPD deficiency is identified.
The FDA noted that it will continue to review emerging safety data related to DPD deficiency and fluoropyrimidine use, with the possibility of further regulatory steps if needed. Healthcare professionals should consult the full prescribing information for detailed guidance across all relevant sections.
References
Safety labeling update for capecitabine and fluorouracil (5-FU) on risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency, 05 February 2026, https://www.fda.gov/drugs/resources-information-approved-drugs/safety-labeling-update-capecitabine-and-fluorouracil-5-fu-risks-associated-dihydropyrimidine
XELODA, Prescribing Information, https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020896s044s045s046s047s048s049s050s051lbl.pdf
