FDA Approves Fluorouracil Safety Label Update Regarding DPD Deficiency Use


The safety label for fluorouracil products will now include information about the agent’s use in patients with dihydropyrimidine dehydrogenase deficiency.

FDA Approves Fluorouracil Safety Label Update Regarding DPD Deficiency Use

FDA Approves Fluorouracil Safety Label Update Regarding DPD Deficiency Use

Safety label changes for fluorouracil injection products have been approved by the FDA to include additional information regarding the risk of serious adverse effects (AEs) in patients with dihydropyrimidine dehydrogenase (DPD) deficiency.1

The regulatory agency announced that the changes to the safety label align with changes made to the prescribing information for capecitabine (Xeloda), which was amended in December 2022.

Updates on the fluorouracil label were added to the following sections: “Warnings and Precautions;” “Patient Counseling Information;” and “Clinical Pharmacology.”

DPD is encoded by the DYPD gene, and the enzyme is responsible for more than 80% of the destructive metabolism of fluorouracil. Partial DPD deficiency occurs in approximately 3% to 5% of White patient populations, and approximately 0.2% of White patients have complete DPD deficiency. Notably, DPD deficiency is estimated to occur at higher rates in Black patient populations; however, sufficient data to estimate the proportion of DPD deficiency in non-White populations are not available.2

The 4 DPYD variants known to be associated with impaired DPD activity include: c.1905+1G>A (DPYD *2A), c.1679T>G (DPYD *13), c.2846A>T, and c.1129-5923C>G (Haplotype B3).

Under “Warnings and Precautions,” the updated label warns that patients with certain homozygous or compound heterozygous DPYD variants associated with complete or near complete absence of DPD activity are at elevated risk for acute, early-onset toxicities, which could be serious or fatal, including mucositis, diarrhea, neutropenia, and neurotoxicity, and the agent is not recommended for use in these patients. Additionally, those with partial DPD deficiency could also be at increased risk of serious or fatal AEs.

In patients treated with fluorouracil injection products who develop acute, early-onset, or unusually severe reactions, fluorouracil should be withheld or discontinued based on the clinical assessment of the onset, duration, and severity of these toxicities, as they could indicate DPD deficiency.

No dosage has been proven safe in patients with complete DPD deficiency, and insufficient data are available regarding a specific dose for patients with partial DPD deficiency.

Testing for DPYD variations should be considered prior to administration of fluorouracil to reduce the risk of serious AEs. However, the FDA has not authorized any tests designed to identify DPYD variations.

The label also advises that patients be advised of the potentially serious or fatal AEs associated with fluorouracil due to DPD deficiency. They should discuss genetic testing for DPYD variants, and patients should be instructed to immediately contact their health care provider if they experience symptoms of severe mucositis, diarrhea, neutropenia, or neurotoxicity.

Fluorouracil was initially approved in 1962 and is indicated for the treatment of patients with colon and rectum adenocarcinoma; breast adenocarcinoma; gastric adenocarcinoma; and pancreatic adenocarcinoma.


  1. FDA approves safety labeling changes regarding DPD deficiency for fluorouracil injection products. FDA. March 21, 2024. Accessed March 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-safety-labeling-changes-regarding-dpd-deficiency-fluorouracil-injection-products
  2. Fluorouracil. Gland Pharma Limited. February 2024. Accessed March 21, 2024. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?xd_co_f=MDMxNmUxNmMtMDgyMS00OThmLWI4MGEtMjY3MGUzYTVkYzdi&setid=ea3497db-23b9-4ace-9a6f-b54853d04a82&type=display#section-11.3
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