FDA adds DPD deficiency warnings to capecitabine and 5-FU labels, says no safe dose is proven

The U.S. Food and Drug Administration (FDA) issued a safety announcement on Nov. 6, 2026 about new label warnings for two widely used cancer drugs, capecitabine and fluorouracil (5-FU). The announcement says both labels now carry expanded information on dihydropyrimidine dehydrogenase (DPD) deficiency, an enzyme disorder that the agency links to serious and fatal reactions to these drugs. ^[1]

The FDA said the purpose of the communication is to raise awareness of the label updates. According to the announcement, all healthcare providers should know the risks of DPD deficiency, tell patients before treatment about the potential for life-threatening toxicity, and discuss testing options with them. ^[1]

The record is a labeling change and a safety communication. It is not a recall, and it does not describe any product being removed from the market. ^[1]

What the records show

Capecitabine and fluorouracil belong to a drug class called fluoropyrimidines. The FDA describes capecitabine as a prodrug of 5-FU. The DPYD gene encodes the DPD enzyme, which the agency says breaks down more than 80% of fluorouracil in the body. ^[1]

Patients who carry certain homozygous or compound heterozygous DPYD variants have what the FDA calls complete DPD deficiency, defined in the record as "complete or near complete absence of DPD activity." The agency says these patients face increased risk of acute early-onset toxicity and serious, including fatal, adverse reactions. The record names mucositis, diarrhea, neutropenia and neurotoxicity as examples. Patients with partial DPD activity may also face increased risk of serious and fatal reactions, according to the FDA. ^[1]

The label updates came through the FDA Oncology Center of Excellence under a program called Project Renewal. The center updated the Xeloda (capecitabine tablets) label first. A separate safety labeling change then brought the same DPD deficiency language into the 5-FU label. ^[1]

According to the announcement, the labeling for both drugs now states:

• Neither drug is recommended for patients known to carry DPYD variants that cause complete DPD deficiency. The label states: "No dose has been proven safe for patients with complete DPD deficiency." ^[1]
• For partial deficiency, the label states: "There is insufficient data to recommend a specific dose in patients with partial DPD deficiency." ^[1]
• Providers should inform patients of the risk and discuss whether the patient should be tested for the associated genetic variants. ^[1]
• Providers should consider testing before starting either drug. ^[1]
• Providers should know the signs and symptoms of DPD-related toxicity, including severe mucositis, diarrhea, neutropenia and neurotoxicity, and advise patients to contact them immediately if these occur. ^[1]
• Providers should withhold or permanently stop the drug, based on clinical assessment of onset, duration and severity, in patients whose reactions are acute, early-onset or unusually severe. The record says such a pattern may indicate complete DPD deficiency. ^[1]
• Four DPYD variants have been linked to impaired DPD activity in White populations, and one variant has been linked to impaired activity in people of African ancestry. ^[1]

The FDA points readers to Sections 5, 12.5 and 17 of the Xeloda and 5-FU prescribing information for the full DPD deficiency text. ^[1]

Why it matters for EMS

The announcement is aimed at prescribers, but the adverse reactions it describes are the kind that can generate emergency calls. The FDA record lists severe mucositis, diarrhea, neutropenia and neurotoxicity as the reactions that may indicate DPD deficiency in a patient taking either drug. ^[1]

The record identifies Xeloda as a tablet product. That means a patient on capecitabine may be taking the drug at home rather than in an infusion setting. The FDA says reactions in patients with complete DPD deficiency can be acute and early in the course of treatment. ^[1]

The label language tells patients to contact their provider immediately if these symptoms appear. The record does not describe any role for prehospital or emergency clinicians, and EMS crews follow local protocols and medical direction. ^[1]

What the records do not tell us

The FDA announcement does not report how many patients have been harmed or have died from DPD-related toxicity, and it does not cite the adverse event data behind the label change. It does not say when the Xeloda label update or the 5-FU safety labeling change took effect. ^[1]

The record does not require genetic testing before treatment. It says providers "should consider testing" and should discuss testing with patients. The announcement does not name a specific test, say which laboratories offer it, or describe the cost or turnaround time. ^[1]

The record does not list the specific DPYD variants by name, and it does not give the prevalence of complete or partial DPD deficiency in any population. It names no manufacturer of fluorouracil or generic capecitabine, and no company comment appears in the record. ^[1]

What to watch

The FDA said it will continue to monitor the safety issue and evaluate the impact of DPD deficiency on the safety of both drugs. The announcement states that "additional regulatory actions will be considered." The agency asked patients and providers to report side effects involving capecitabine or 5-FU products to its MedWatch program. No date for a further decision appears in the record. ^[1]

This is news, not medical advice. EMS clinicians: follow your local protocols and medical direction.