Safety announcement: FDA highlights importance of DPD deficiency discussions with patients prior to capecitabine or 5FU treatment
Regulatory safety update (FDA, Jan 24, 2025): the FDA issued a communication to raise awareness of updated labeling for capecitabine (Xeloda) and fluorouracil (5‑FU) regarding risks from dihydropyrimidine dehydrogenase (DPD) deficiency. The agency highlights discussing DPD deficiency and testing options with patients before starting therapy, and notes labeling statements that these fluoropyrimidines are not recommended in patients with complete DPD deficiency and that data are insufficient to recommend a specific dose in partial DPD deficiency.
FDA safety update on DPD deficiency and fluoropyrimidines (Jan 24, 2025)
Type: Regulatory safety update (labeling communication), not an approval.
The U.S. Food and Drug Administration (FDA) issued a safety communication to increase awareness of recent updates to the product labeling for capecitabine (Xeloda) and fluorouracil (5‑FU) regarding risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency.
Fluoropyrimidines include 5‑FU and capecitabine (a prodrug of 5‑FU). The DPYD gene encodes DPD, which breaks down >80% of fluorouracil. The FDA states that patients with certain homozygous or compound heterozygous DPYD variants causing complete or near-complete absence of DPD activity (complete DPD deficiency) are at increased risk for acute early-onset toxicity and serious, including fatal, adverse reactions (e.g., mucositis, diarrhea, neutropenia, neurotoxicity). Patients with partial DPD deficiency may also have increased risk of serious, including fatal, reactions.
Under Project Renewal, FDA updated Xeloda labeling and made a safety labeling change to align 5‑FU labeling with DPD deficiency information. Labeling states:
- Capecitabine/5‑FU are not recommended in patients known to have certain DPYD variants resulting in complete DPD deficiency; no dose has been proven safe.
- Insufficient data exist to recommend a specific dose in partial DPD deficiency.
The FDA notes it will continue monitoring this issue and may consider additional regulatory actions; it also encourages reporting to FDA MedWatch.