Safety labeling update for capecitabine and fluorouracil (5-FU) on risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency
Regulatory approval: On Feb 5, 2026, the FDA approved safety labeling revisions for capecitabine (Xeloda) and fluorouracil (5-FU) to address risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency. Updates emphasize that patients with complete DPD deficiency (due to certain homozygous or compound heterozygous DPYD variants) are at increased risk of early-onset severe, including fatal, toxicity. Labeling now highlights DPYD testing prior to initiation unless immediate treatment is necessary, and provides guidance to avoid use in complete DPD deficiency and individualize dosing in partial deficiency.
FDA labeling update (regulatory approval)
Date: 2026-02-05
Agency: U.S. Food and Drug Administration (FDA)
The FDA announced approved revisions to product labeling for capecitabine (Xeloda) and fluorouracil (5-FU) regarding risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency.
Rationale
The DPYD gene encodes DPD, which breaks down >80% of fluorouracil. Patients with certain homozygous or compound heterozygous DPYD variants that result in complete or near-complete absence of DPD activity (complete DPD deficiency) are reported to be at increased risk for acute early-onset toxicity and serious, including fatal, adverse reactions (e.g., mucositis, diarrhea, neutropenia, neurotoxicity) when exposed to capecitabine or 5-FU. Patients with partial DPD deficiency may also have increased risk of serious, including fatal, adverse reactions.
Key labeling changes
- Boxed Warning: Highlights risk of serious adverse reactions or death in complete DPD deficiency; advises DPYD testing prior to initiating capecitabine or 5-FU unless immediate treatment is necessary; recommends avoiding use in patients with certain variants causing complete DPD deficiency.
- Dosage and Administration: Adds subsection 2.1 on evaluation/testing before initiation; advises to avoid use in known complete DPD deficiency and individualize dosing in partial deficiency.
- Warnings and Precautions: Reiterates DPYD testing prior to initiation unless immediate treatment is necessary.
The FDA stated it will continue monitoring this safety issue and may consider additional regulatory actions.