posted Aug 8, 2016, 10:09 PM by Vinod Scaria
updated Aug 8, 2016, 10:14 PM
- Fluorouracil (5-FU) is a commonly used anticancer drug. It functions by irreversibly inhibiting thymidylate synthase.
- 5-FU is widely used in a number of cancers worldwide and is in the WHO list of Essential Medicines.
- Detoxification of 5-FU is mediated by the dihydropyrimidine dehydrogenase (DPD) gene.
- Apart from 5-FU, the gene also is involved in detoxification of Capecitabine, and Tegafur.
- Genetic variations in the gene can cause a partial or complete deficiency of function, which may lead to drug toxicity, which are severe.
Pharmacogenetic testing is recommended on the FDA Drug label
The USFDA-approved drug label for fluorouracil states that the drug is contraindicated in patients with known DPD deficiency.
CPIC Dosing Guidelines for fluoropyrimidines recommends an alternative drug for patients who are homozygous for DPYD non-functional variants as these patients are typically DPD deficient and a 50% reduction for heterozygous patients.Information Brochure