Floxuridine is a highly toxic drug with a narrow margin
of safety. Therefore, patients should be carefully supervised since therapeutic
response is unlikely to occur without some evidence of toxicity. Severe
hematological toxicity, gastrointestinal hemorrhage and even death may result
from the use of floxuridine despite meticulous selection of patients and
careful adjustment of dosage. Although severe toxicity is more likely in poor
risk patients, fatalities may be encountered occasionally even in patients in
relatively good condition.
Therapy is to be discontinued promptly whenever one of
the following signs of toxicity appears:
Stomatitis or esophagopharyngitis, at the first visible
Leukopenia (WBC under 3500) or a rapidly falling white
Diarrhea, frequent bowel movements or watery stools
Gastrointestinal ulceration and bleeding
Thrombocytopenia (platelets under 100,000)
Hemorrhage from any site
Careful monitoring of the white blood count and platelet
count is recommended.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals to evaluate the carcinogenic
potential of floxuridine have not been conducted. On the basis of the available
data, no evaluation can be made of the carcinogenic risk of floxuridine to
Oncogenic transformation of fibroblasts from mouse embryo
has been induced in vitro by floxuridine, but the relationship between
oncogenicity and mutagenicity is not clear. Floxuridine has also been shown to
be mutagenic in human leukocytes in vitro and in the Drosophila test system. In
addition, 5- fluorouracil, to which floxuridine is catabolized when given by
intraarterial injection, has been shown to be mutagenic in in vitro tests.
Impairment Of Fertility
The effects of floxuridine on fertility and general
reproductive performance have not been studied in animals. However, because
floxuridine is catabolized to 5-fluorouracil, it should be noted that 5- fluorouracil
has been shown to induce chromosomal aberrations and changes in chromosome organization
of spermatogonia in rats at doses of 125 or 250 mg/kg, administered
Spermatogonial differentiation was also inhibited by
fluorouracil, resulting in transient infertility. In female rats, fluorouracil,
administered intraperitoneally at doses of 25 or 50 mg/kg during the preovulatory
phase of oogenesis, significantly reduced the incidence of fertile matings,
delayed the development of pre- and post-implantation embryos, increased the
incidence of preimplantation lethality and induced chromosomal anomalies in
these embryos. Compounds such as floxuridine, which interfere with DNA, RNA and
protein synthesis, might be expected to have adverse effects on gametogenesis.
Pregnancy category D.
See WARNINGS. Floxuridine has been shown to be
teratogenic in the chick embryo, mouse (at doses of 2.5 to 100 mg/kg) and rat
(at doses of 75 to 150 mg/kg). Malformations included cleft palates, skeletal
defects and deformed appendages, paws and tails. The dosages which were teratogenic
in animals are 3.2 to 125 times the recommended human therapeutic dose.
There are no adequate and well-controlled studies with
floxuridine in pregnant women. While there is no evidence of teratogenicity in
humans due to floxuridine, it should be kept in mind that other drugs which
inhibit DNA synthesis (eg, methotrexate and aminopterin) have been reported to
be teratogenic in humans. Floxuridine should be used during pregnancy only if
the potential benefit justifies the potential risk to the fetus.
Floxuridine has not been studied in animals for its
effects on peri- and postnatal development. However, compounds which inhibit
DNA, RNA and protein synthesis might be expected to have adverse effects on
peri- and postnatal development.
It is not known whether floxuridine is excreted in human
milk. Because floxuridine inhibits DNA and RNA synthesis, mothers should not
nurse while receiving this drug.
Safety and effectiveness in pediatric patients have not