FDA Updates Safety Warnings for Common Chemotherapy Drugs

The U.S. Food and Drug Administration (FDA) has issued an updated safety communication regarding two commonly used chemotherapy drugs, Xeloda (capecitabine) and fluorouracil (5-FU), according to the regulatory agency. The update focuses on risks associated with a rare genetic condition known as dihydropyrimidine dehydrogenase (DPD) deficiency, which can significantly increase the likelihood of severe or life-threatening side effects from these treatments.

Xeloda and 5-FU are widely used to treat several cancers, including colorectal, breast, gastric, esophageal, and pancreatic cancers. The FDA is emphasizing the importance of testing for specific genetic variants in the DPYD gene before starting treatment, unless immediate therapy is required. These labeling changes are intended to help clinicians better identify patients at increased risk and to improve treatment safety.

Key labeling changes for Xeloda and fluorouracil

A major update appears in the Boxed Warning, the most prominent safety warning required by the FDA. The warning now highlights the risk of serious adverse reactions or death in patients with complete DPD deficiency and advises genetic testing for DPYD variants prior to treatment initiation when possible.

In addition, a new subsection has been added to the Dosage and Administration section instructing clinicians to avoid using Xeloda or 5-FU in patients known to have certain homozygous or compound heterozygous DPYD variants that result in complete absence of DPD activity. For patients with partial DPD deficiency, the labeling recommends individualized dosing based on clinical judgment.

The Warnings and Precautions section also reinforces the importance of DPYD genetic testing before starting therapy. These updates aim to reduce the risk of early, severe toxicities by identifying vulnerable patients before exposure to fluoropyrimidine chemotherapy.

What is DPD deficiency? Why does it matter?

DPD deficiency is a genetic condition caused by variants in the DPYD gene, which encodes the enzyme dihydropyrimidine dehydrogenase. This enzyme is responsible for breaking down more than 80% of fluorouracil in the body. When DPD activity is absent or reduced, fluorouracil and Xeloda can accumulate to dangerous levels.

Patients with complete DPD deficiency have little to no enzyme activity and face a high risk of early-onset toxicities, including severe diarrhea, mouth sores (mucositis), low white blood cell counts (neutropenia), and neurologic complications. In some cases, these reactions can be fatal. Patients with partial DPD deficiency may also be at increased risk, although the severity can vary.

Because DPD deficiency is not easily identified based on symptoms alone, genetic testing plays an important role in recognizing patients who may need alternative treatments or dose adjustments.

How are testing and treatment decisions are made?

The updated labeling instructs healthcare providers to test patients for known DPYD genetic variants before starting Xeloda or 5-FU, unless treatment must begin immediately. If testing identifies complete DPD deficiency, use of these drugs should be avoided, as no safe dose has been established for these patients.

For individuals with partial DPD deficiency, clinicians may consider lower starting doses with careful monitoring. The FDA notes that treatment decisions should be individualized, taking into account the patient’s overall health, cancer type, and urgency of therapy.

Patients are encouraged to discuss genetic testing with their oncology team and to ask whether DPYD testing has been performed prior to starting treatment.

Who may be affected and additional safety information

Xeloda and 5-FU are prescribed across a wide range of cancer types, meaning many patients could be impacted by these updates. The FDA will continue monitoring safety data and may consider additional regulatory actions as new information becomes available.

Although these drugs remain important components of cancer treatment, the updated labeling underscores the growing role of genetic testing in improving safety and personalizing care.

References

1. “Safety labeling update for capecitabine and fluorouracil (5-FU) on risks associated with dihydropyrimidine dehydrogenase (DPD) deficiency,” by the U.S. Food and Drug Administration. News release; Feb. 5, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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