Fucil Special Precautions

5-FU is a potent drug and should be prescribed only by physicians experienced with cancer chemotherapeutic drugs. Blood counts as well as renal and hepatic function tests should be performed regularly. Discontinue the drug if there is significant leukopenia (under 3500/mm³) or granulocytopenia (under 1500/mm³).
GI Effects: Anorexia and nausea are common adverse effects of 5-FU and vomiting occurs frequently. These reactions generally occur during the first week of therapy, can often be alleviated by antiemetics and generally subside within 2 or 3 days following therapy. Stomatitis is one of the most common and often the earliest sign of specific toxicity, appearing as early as the 4^th day but more commonly on the 5^th to 8^th day of therapy. Diarrhea, which also occurs frequently, usually appears slightly later than stomatitis, but may occur more concurrently or even in the absence of stomatitis. Patients should be questioned and the mouth examined daily for early evidence of stomatitis. Appearance of stomatitis, as evidenced by either oral mucosal erythema or ulceration at the inner margin of the lips, or of esophagopharyngitis as evidenced by sore throat or dysphagia, necessitates cessation of therapy.
Hematologic Effects: Leukopenia (predominantly granulocytopenia), thrombocytopenia and anemia occur commonly with 5-FU therapy; leukopenia usually occurs after an adequate course of 5-FU therapy. The nadir of the white blood cell count usually occurs from the 9^th to the 14^th day after therapy is initiated but may occur as late as the 25^th day after the first dose of 5-FU; counts usually return to normal after about 30 days. Maximum thrombocytopenia has been reported to occur from the 7^th to 17^th day of therapy. Hematopoietic recovery is usually rapid and by the 13^th day, blood cell counts have usually reached the normal range.
Leukocyte counts with differential should be made before each dose of 5-FU is given. If the leukocyte count drops to < 2000/mm³, the patient should be placed in protective isolation and appropriate measures taken for the prevention of infection. During maintenance therapy, counts before each course are sufficient.
Cardiac Effects: 5-FU should not be readministered after a documented cardiovascular reaction (arrhythmia, angina, ST segment changes) as there is a risk of sudden death. 5-FU should be used with caution in patients who experience chest pain during courses of treatment of those with heart disease.
Neurological Effects: In cases of severe neurological toxicity, continued treatment with 5-FU is not recommended (see Adverse Reactions).
Effects on the Ability to Drive and Use Machines: 5-FU may induce nausea and vomiting which could interfere with driving or the use of heavy machinery.
Other Populations: 5-FU should be used with extreme caution and the initial dose may be reduced by one-third to one-half in the following patients: Undergone recent major surgery (within previous 30 days).
Patients who have previously received high-dose irradiation therapy to bone marrow-bearing areas (pelvis, spine, ribs, etc.) or alkylating agents.
Impaired hepatic or renal function (see Dosage & Administration).
History of heart disease (see Precautions).
Widespread metastatic involvement of the bone marrow.
Patients who are known or suspected to have a dihydropyrimidine dehydrogenase deficiency.
Carcinogenicity, Mutagenicity and Impairment of Fertility: Carcinogenicity: Long-term studies in animals to determine the carcinogenic potential of 5-FU have not been performed; however, no evidence of carcinogenicity was observed in several animal studies following oral or IV administration of the drug for up to 1 year. In vitro, the drug has induced oncogenic transformation of fibroblasts from mouse embryo. The carcinogenic risk in humans is not known.
Mutagenicity: 5-FU has been shown to be mutagenic and clastogenic in a number of studies. In addition, the drug was mutagenic in the micronucleus test on mouse bone marrow cells and at very high concentrations, produced chromosomal breaks in hamster fibroblasts in vitro. Although the risk of mutagenesis in patients receiving 5-FU has not been evaluated, the possibility must be considered.
Impairment of Fertility: 5-FU has not been adequately studied in animals to determine the effects on fertility and general reproductive performance. Following intraperitoneal administration of 125 or 250 mg/kg in rats, chromosomal aberrations and changes in chromosomal organization of spermatogonia were induced; spermatogonial differentiation was also inhibited, resulting in transient infertility. In a strain of mouse that is insensitive to the induction of sperm head abnormalities after exposure to a number of chemical mutagens and carcinogens, no abnormalities were produced at oral dosages of up to 80 mg/kg daily. Following intraperitoneal administration at weekly doses of up to 25 or 50 mg/kg for 3 weeks during the preovulatory phases of oogenesis in female rats, the incidence of female matings was substantially reduced, development of preimplantation and postimplantation embryos was delayed, and the incidence of preimplantation lethality and chromosomal anomalies in the embryo was increased. In a limited study in rabbits, a single 25 mg/kg dose or daily doses of 5 mg/kg for 5 days had no effect on ovulation, appeared not to affect implantation, and had only a limited effect in producing zygote destruction. Drugs that inhibit DNA, RNA and protein synthesis such as 5-FU may have adverse effects on gametogenesis.
Use in Children: The safety and efficacy of 5-FU in children have not been established.
Use in Elderly: 5-FU should be used with caution in elderly patients. An age of 70 years or older and the female gender are reported independent risk factors for severe toxicity from 5-FU-based chemotherapy. These effects may be additive in older women. Close monitoring for multiple organ toxicities and vigorous supportive care from those with toxicity are necessary.