There exists the potential for a delayed hypersensitivity reaction to fluorouracil.
Patch testing to prove hypersensitivity may be inconclusive1.
If an occlusive dressing is used, there may be an increase in the incidence of inflammatory reactions in the adjacent normal skin.
The patient should avoid prolonged exposure to sunlight or other forms of ultraviolet irradiation during treatment with FLUOROPLEX® (fluorouracil topical cream) Cream, as the intensity of the reaction may be increased.
There is a possibility of increased absorption through ulcerated or inflamed
To rule out the presence of a frank neoplasm, a biopsy should be made of those areas failing to respond to treatment or recurring after treatment.
Carcinogenesis, mutagenesis, impairment of fertility
Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. In three in-vitro cell transformation assays, fluorouracil produced morphological transformation of cells. Morphological transformation was also produced in one of these in-vitro assays by a metabolite of fluorouracil and the transformed cells produced malignant tumors when injected into immunosuppressed syngeneic mice. Fluorouracil has been shown to exert mutagenic acitivity in the yeast cells, Bacillus subtilis and Drosophila assays. In addition, fluorouracil has produced chromosome damage at concentrations of 1.0 and 2.0 mcg/mL in an in vitro hamster fibroblast assay and increases in micronuclei formation in the bone marrow of mice at intraperitoneal doses within the human therapeutic dose range of 12-15 mg/kg/day. Patients receiving cumulative doses of 0.24-1.0 g of fluorouracil parenterally have shown an increase in numerical and structural chromosome aberrations in peripheral blood lymphocytes. Fluorouracil has been shown to impair fertility after parenteral administration in rats. In mice, single-dose intravenous and intraperitoneal injections of fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes at a dose of 500 mg/kg and produce abnormalities in spermatids at 50 mg/kg.
Fluorouracil was negative in the dominant lethal mutation assay performed in mice.
Teratogenic effects: Pregnancy Category X: Fluorouracil may cause
fetal harm when administered to a pregnant woman. Fluorouracil administered
parenterally has been shown to be teratogenic in mice, rats and hamsters, and
embryolethal in monkeys. Fluorouracil is contraindicated in women who are or
may become pregnant. If this drug is used during pregnancy, or if the patient
becomes pregnant while taking this drug, the patient should be apprised of the
potential hazard to the fetus.
It is not known whether this drug is excreted in human milk. Because many drugs
are excreted in human milk, and because there is some systemic absorption of
fluorouracil after topical administration (see PRECAUTIONS: General),
mothers should not nurse their infants while receiving this drug.
Safety and effectiveness in pediatric patients have not been established.
1. Epstein E. Testing for 5-fluorouracil allergy: patch and intradermal tests. Contact Dermatitis 1984; 10:311.