Antineoplastic (Antimetabolite)
PREGNANCY RECOMMENDATION: Contraindicated—1st Trimester
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of floxuridine in human pregnancy have been located. The drug has caused some form of developmental toxicity (structural anomalies, functional deficits, and death) in several animal species. Although the magnitude of human risk is unknown, floxuridine is best avoided in pregnancy, especially in the 1st trimester, because it interferes with DNA, RNA, and protein synthesis.
FETAL RISK SUMMARY
Floxuridine, a fluorinated pyrimidine, is a prodrug antineoplastic antimetabolite that is given by intra-arterial infusion. It is rapidly metabolized to one of two active agents, 5-fluorouracil or floxuridine-monophosphate, and several inactive metabolites (see also Fluorouracil). It is classified as an antimetabolite in the subclass of pyrimidine analogs. In addition to fluorouracil, other antineoplastic agents in the subclass are capecitabine and gemcitabine. Floxuridine is indicated for the palliative management of gastrointestinal adenocarcinoma metastatic to the liver. Pharmacokinetic data are not available (1,2).
Reproduction studies have been conducted in the chick embryo, mice, and rats. The drug was teratogenic in the three species at doses that were 4.2–125 times the recommended human therapeutic dose. Malformations included cleft palates, skeletal defects and deformed appendages, paws, and tails (2). In addition, a 1998 study concluded that the postpubertal reproduction dysfunction observed in male mice that had been exposed to floxuridine as embryos resulted from excessive cell death in the developing brain (3).
Long-term carcinogenicity studies have not been conducted with floxuridine. Floxuridine and its active metabolite, fluorouracil, are known to be mutagenic. With the exception of the above study, reproductive performance and fertility studies have not been conducted with floxuridine. However, fluorouracil is known to cause chromosomal aberrations and changes in chromosome organization of spermatogonia, as well as transient infertility in rats. In female rats, intraperitoneal doses of fluorouracil administered in the preovulatory phase of oogenesis significantly reduced the number of fertile matings, delayed the development of embryos, increased the incidence of preimplantation lethality, and induced chromosomal anomalies in the embryos (2).
It is not known if floxuridine or its active metabolites cross the human placenta. The molecular weight of the parent compound (about 246) suggests that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of floxuridine during human lactation have been located. The antineoplastic agent is converted into two active metabolites, 5-fluorouracil and floxuridine-monophosphate (see also Fluorouracil). The molecular weight of the parent compound (about 246) suggests that the drug will be excreted into breast milk. If a nursing woman is treated with floxuridine, breastfeeding should be avoided because the drug interferes with DNA, RNA, and protein synthesis.
References
1.Product information. FUDR. Roche Laboratories, 1987.
2.Product information. Floxuridine. Bedford Laboratories, 2000.
3.Nagao T, Kuwagata M, Saito Y. Effects of prenatal exposure to 5-fluoro-2′-deoxyuridine on developing central nervous system and reproductive function in male offspring of mice. Teratog Carcinog Mutagen 1998;18:73–92.