"The U.S. Food and Drug Administration today expanded the approved use of Opdivo (nivolumab) to treat patients with advanced (metastatic) squamous non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy.
BECAUSE OF THE POSSIBILITY OF SEVERE TOXIC REACTIONS, ALL PATIENTS SHOULD BE HOSPITALIZED FOR THE FIRST COURSE OF THERAPY.
Floxuridine should be used with extreme caution in poor risk patients with impaired hepatic or renal function or a history of high-dose pelvic irradiation or previous use of alkylating agents. The drug is not intended as an adjuvant to surgery.
Floxuridine may cause fetal harm when administered to a pregnant woman. It 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 4.2 to 125 times the recommended human therapeutic dose.
There are no adequate and well-controlled studies with floxuridine in pregnant women. If this drug is used during pregnancy or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Combination Therapy: Any form of therapy which adds to the stress of the patient, interferes with nutrition or depresses bone marrow function will increase the toxicity of floxuridine.
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 sign
Leukopenia (WBC under 3500) or a rapidly falling white blood count
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
Carcinogenesis: 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 humans.
Mutagenesis: 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 leukocytesin vitro and in the Drosophila test system. In addition, 5-fluorouracil, to which floxuridine is catabolized when given by intra-arterial 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 the 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 intraperitoneally.
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.
Teratogenic Effects: Pregnancy Category D.
See WARNINGS section. 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 were 4.2 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 (e.g., 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 been established.
Last reviewed on RxList: 11/13/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Floxuridine Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.