5-Fluorouracil (5-FU) is used for: Palliation of malignant neoplasms, Superficial basal cell carcinoma, Oesophageal carcinoma, Carcinoma of Colon, Carcinoma of Breast, Carcinoma of Ovary, Carcinoma of Liver, Carcinoma of Pancreas, Carcinoma of Rectum, Carcinoma of Stomach
Adult: IV Palliation of malignant neoplasms 12 mg/kg/day (max: 0.8-1g/day) for 3-4 days, if no toxicity occurs, may be followed after 1 day w/ 6 mg/kg on alternate days for another 3-4 doses. May repeat course 4-6 wk later or maintenance doses of 5-15 mg/kg (max: 1 g) may be given wkly. Cancers of Colon, Breast, Ovary, Liver, Pancreas, Rectum, Stomach Various protocols exist 500 mg/sq.meter IV on Days 1-5, OR 450-600 mg/sq.meter IV weekly, OR 200-400 mg/sq.meter IV continuous infusion qD Not to exceed 800 mg/day As an infusion: 15 mg/kg/day (max: 1 g/day), continue until toxicity occurs or a total of 12-15 g is given. May repeat course 4-6 wk later. Intra-arterial Palliation of malignant neoplasms 5-7.5 mg/kg/day as continuous infusion (regional perfusion). Hepatic impairment: Dose reduction may be required.
Child: Safety & efficacy not established.
Renal impairment: Dose reduction may be required.
IV Preparation IV Push: dose/syringe (concentration: 50 mg/mL); max syringe size for IVP is 30 mL syringe and syringe should be <75% full Continuous IV Infusion/IVPB: dose/50-1000 mL D5W or NS; syringe and solution are stable for 72 hr at 4 to 25°C IV Administration Direct IV push injection (50 mg/mL solution needs no further dilution) or by IV infusion Toxicity may be reduced by giving the drug as a constant infusion Bolus doses may be administered by slow IVP or IVPB Warm to body temperature before using Continuous IV infusion may be administered in D5W or NS Solution should be protected from direct sunlight 5-FU may also be administered intra-arterially or intra-hepatically Use plastic IV containers for continuous infusions (stable in plastic IV bags than in glass bottles)
Topical application on mucous membranes, exposure to sunlight, hypersensitivity. Depressed bone marrow function, poor nutritional status, potentially serious infections. Pregnancy and lactation.
Regular monitoring of blood counts. History of heart disease, hepatic or renal insufficiency, weak or malnourished patients, patients who with history of high-dose pelvic radiation or use of alkylating agents. Patients with widespread metastases to the bone marrow. Lactation: excretion in milk unknown; do not nurse.
Pregnancy Category: D Risk Summary There are no adequate and well-controlled studies with fluorouracil in pregnant women. Based on its mechanism of action, fluorouracil can cause fetal harm when administered to a pregnant woman. Lactation: excretion in milk unknown; do not nurse
May increase warfarin effects. May reduce response to vaccines; possibility of generalized infection with live vaccines. Action may be modified by allopurinol. Leucovorin calcium may enhance the toxicity of fluorouracil.
Side effects of 5-Fluorouracil (5-FU) : 1-10% Loss of appetite, Headache, Nausea, Vomiting, Diarrhea, Mucositis, Myelosuppression, Alopecia, Photosensitivity, Hand-foot syndrome, Maculopapular eruption (pruritic) Frequency Not Defined Angina, Coronary arteriosclerosis, Thrombophlebitis, Darkening of veins, Gastrointestinal ulcer, Increased alkaline phosphatase, Increased LFTs, Hyperbilirubinemia, Hypercholesterolemia (increased LDH), Anaphylaxis, Nystagmus, Ophthalmic findings Potentially Fatal: Central neurotoxicity, myocardial ischaemia.
Mechanism of Action
Fluorouracil interferes with DNA synthesis by blocking the conversion of deoxyuridylic acid to thymidylic acid. It also interferes with RNA synthesis. This results in an unbalanced growth of the cells. Fluorouracil exerts greater effect on rapidly growing cells as they take up the drug at a faster rate.