Fluorouracil

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

The FDA recommends, but does not require, genetic testing prior to initiating treatment with fluorouracil (Efudex).

Fluorouracil is used for the treatment of various types of neoplasms including colorectal neoplasms. Variants in the DPYD gene (also known as dihydropyrimidine dehydrogenase and DPD) are associated with increased risk for adverse events. See the Fluroropyrimidine Pathway and DPYD VIP for more information.

Excerpts from the fluorouracil (Efudex) drug label:
"Efudex should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. A large percentage of fluorouracil is catabolized by the DPD enzyme. DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities."

"Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency. One case of life-threatening systemic toxicity has been reported with the topical use of Efudex in a patient with DPD enzyme deficiency. Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills. Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel. Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Fluorouracil drug label PDF.

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