Adequate studies investigating the carcinogenic potential of capecitabine have not been conducted. Capecitabine was not mutagenic in vitro to bacteria (Ames test) or mammalian cells (Chinese hamster V79/HPRT gene mutation assay). Capecitabine was clastogenic in vitro to human peripheral blood lymphocytes but not clastogenic in vivo to mouse bone marrow (micronucleus test). Fluorouracil causes mutations in bacteria and yeast. Fluorouracil also causes chromosomal abnormalities in the mouse micronucleus test in vivo.^L44657

In studies of fertility and general reproductive performance in female mice, oral capecitabine doses of 760 mg/kg/day (about 2,300 mg/m2/day) disturbed estrus and consequently caused a decrease in fertility. In mice that became pregnant, no fetuses survived this dose. The disturbance in estrus was reversible. In males, this dose caused degenerative changes in the testes, including decreases in the number of spermatocytes and spermatids. In separate pharmacokinetic studies, this dose in mice produced 5’-DFUR AUC values about 0.7 times the corresponding values in patients administered the recommended daily dose.^L44657

Based on findings in animal reproduction studies and its mechanism of action see Clinical Pharmacology (12.1), XELODA can cause fetal harm when administered to a pregnant woman. Available human data on XELODA use in pregnant women is not sufficient to inform the drug-associated risk. In animal reproduction studies, administration of capecitabine to pregnant animals during the period of organogenesis caused embryo lethality and teratogenicity in mice and embryo lethality in monkeys at 0.2 and 0.6 times the exposure (AUC) in patients receiving the recommended dose of 1,250 mg/m2 twice daily, respectively. Advise pregnant women of the potential risk to a fetus.^L44657

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.^L44657

Administer uridine triacetate within 96 hours for management of XELODA overdose. Although no clinical experience using dialysis as a treatment for XELODA overdose has been reported, dialysis may be of benefit in reducing circulating concentrations of 5’-DFUR, a low–molecular-weight metabolite of the parent compound.^L44657