FDA label 4f17a66d-5d04-430f-8384-4032be81bcd6

WARNING It is recommended that Fluorouracil Injection be given only by or under the supervision of a qualified physician who is experienced in cancer chemotherapy and who is well versed in the use of potent antimetabolites. Because of the possibility of severe toxic reactions, it is recommended that patients be hospitalized at least during the initial course of therapy. These instructions should be thoroughly reviewed before administration of Fluorouracil Injection, USP.

WARNINGS ( see BOXED WARNING ) THE DAILY DOSE OF FLUOROURACIL INJECTION IS NOT TO EXCEED 800 MG. IT IS RECOMMENDED THAT PATIENTS BE HOSPITALIZED DURING THEIR FIRST COURSE OF TREATMENT. Fluorouracil should be used with extreme caution in poor risk patients with a history of high-dose pelvic irradiation or previous use of alkylating agents, those who have a widespread involvement of bone marrow by metastatic tumors or those with impaired hepatic or renal function. Rarely, unexpected, severe toxicity (e.g., stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil has been attributed to deficiency of dipyrimidine dehydrogenase activity.1 A few patients have been rechallenged with 5-fluorouracil and despite 5-fluorouracil dose lowering, toxicity recurred and progressed with worse morbidity. Absence of this catabolic enzyme appears to result in prolonged clearance of 5-fluorouracil. Pregnancy Teratogenic Effects – Pregnancy Category D Fluorouracil may cause fetal harm when administered to a pregnant woman. Fluorouracil has been shown to be teratogenic in laboratory animals. Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on day 10 or 12 of gestation. Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg given to hamsters between days 8 and 11 of gestation were teratogenic. Malformations included cleft palates, skeletal defects and deformed appendages, paws and tails. The dosages which were teratogenic in animals are 1 to 3 times the maximum recommended human therapeutic dose. In monkeys, divided doses of 40 mg/kg given between days 20 and 24 of gestation were not teratogenic. There are no adequate and well-controlled studies with fluorouracil in pregnant women. While there is no evidence of teratogenicity in humans due to fluorouracil, 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. Women of childbearing potential should be advised to avoid becoming pregnant. If the drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be told of the potential hazard to the fetus. Fluorouracil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 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 fluorouracil.

ADVERSE REACTIONS Stomatitis and esophagopharyngitis (which may lead to sloughing and ulceration), diarrhea, anorexia, nausea and emesis are commonly seen during therapy. Leukopenia usually follows every course of adequate therapy with fluorouracil. The lowest white blood cell counts are commonly observed between the 9 th and 14 th days after the first course of treatment, although uncommonly the maximal depression may be delayed for as long as 20 days. By the 30 th day the count has usually returned to the normal range. Alopecia and dermatitis may be seen in a substantial number of cases. The dermatitis most often seen is a pruritic maculopapular rash usually appearing on the extremities and less frequently on the trunk. It is generally reversible and usually responsive to symptomatic treatment. Other adverse reactions are: Hematologic: pancytopenia, thrombocytopenia, agranulocytosis, anemia. Cardiovascular: myocardial ischemia, angina. Gastrointestinal: gastrointestinal ulceration and bleeding. Allergic Reactions: anaphylaxis and generalized allergic reactions. Neurologic: acute cerebellar syndrome (which may persist following discontinuance of treatment), nystagmus, headache. Dermatologic: dry skin; fissuring; photosensitivity, as manifested by erythema or increased pigmentation of the skin; vein pigmentation; palmar-plantar erythrodysesthesia syndrome, as manifested by tingling of the hands and feet followed by pain, erythema and swelling. Ophthalmic: lacrimal duct stenosis, visual changes, lacrimation, photophobia. Psychiatric: disorientation, confusion, euphoria. Miscellaneous: thrombophlebitis, epistaxis, nail changes (including loss of nails).