5-Fluril® (5-Fluorouracil BP), an antineoplastic antimetabolite, is a colorless to faint yellow aqueous, sterile, nonpyrogenic injectable solution available in a 10 mL package for intravenous administration.Chemically, fluorouracil, a fluorinated pyrimidine, is 5-fluoro 2,4 (1H,3H)-pyrimidinedione. It is a white crystalline powder which is sparingly soluble in water. Its molecular formula is C4H3FN2O2, and molecular weight is 130.08 and the structural formula is
Each Vial contains 10 ml Fluorouracil BP 250mg Injection.
Mechanism of action
5-Fluril® works by inhibiting the enzyme thymidylate kinase which results in reduced formation of thymidine and thus DNA. The active metabolite FdUMP appears to form a stable complex with the folate cofactor N-5, 10-methylene tetrahydrofolate which inactivates thymidylate kinase. 5-Fluril as FdUMP is also incorporated into RNA which results in fluorination of RNA. The effect of fluorouracil on living cells is limited mainly to those in the proliferative phase but while cells in the G2 and S phase are most affected there may be effects at any stage of the cell cycle.
Protein binding 8-12%
Metabolism Intracellular and hepatic (CYPmediated)
Half-life 10-20 minutes
5-Fluril® is indicated alone or in combination for carcinoma of the colon or rectum, carcinoma of the stomach and exocrine pancreas, carcinoma of the liver, carcinoma of the breast (an especially aggressive form of breast cancer), carcinoma of the bladder, carcinoma of the lung, epithelial ovarian carcinoma andcervical carcinoma.
Dosage and administration
Intravenous 5-Fluril® can be delivered by rapid intravenous bolus injection or slow infusion. The vial contents can rapidly be injected directly into a peripheral vein, the commonest schedules being 500 mg/m2 daily for 5 days repeated at 4-weekly intervals. Slow intravenous infusion requires the drug to be diluted in 500 mL of dextrose 5% solution, then infused over 2-3 hours on 5 successive days.
Usual dosage and schedule:
Systemic: 500 mg/m2 I.V. on days 1 to 5 every 4 weeks or 450 to 600 mg/m2 I.V. weekly. 200 to 400 mg/m2 daily as a continuous I.V. infusion. 1000 mg/m2 daily for 4 days as a continuous I.V. infusion every 3 to 4 weeks. Leucovorin 20 mg/m2 I.V. is followed by fluorouracil 425 mg/m2 I.V. The combination is given daily for 5 days. Courses
are repeated every 4 weeks.
Intracavitary: 500 to 1000 mg for pericardial effusion; 2000 to 3000 mg for pleural or peritoneal effusions.
Intra- arterial (liver): 800 to 1200 mg/m2 as a continuous infuson on days 1 to 4, followed by 600 mg/m2 as a continuous infusion on days 5 to 21.
Possible side effects
Mild to moderate cardiac effects, hepatic effects, hematological effects, neurological effects, allergic reaction, decreased bone marrow function, hand-foot syndrome, severe vomiting, diarrhoea, frequent bowel movements or watery stools, sores in the mouth or throat may occur.
5-Fluorouracil is contraindicated for patients in a poor nutritional state, those with depressed bone marrow function, those with potentially serious infections or those with a known hypersensitivity to this drug.CYPmediated)
Pre-treatment with cimetidine for 4 weeks lead to increased plasma concentrations of fluorouracil following intravenous and oral administration. The effect was probably due to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.
Dose should be reduced in patients with compromised liver function. For intra-arterial infusion, 5000 U of L.M. heparin should be added to 1 L of 5% dextrose in water together with the daily dose of fluorouracil. Ulcer-like pain or other significant gastrointestinal symptoms are indications to discontinue intra-arterial therapy, as hemorrhage or perforation may occur. Precipitation may occur when leucovorin and fluorouracil are mixed in the same bag.
How to use
Each Vial contains 10 ml Fluorouracil BP 250 mg & 500 mg and it should be diluted in 500 mL of dextrose 5% solution, then infused over 2-3 hours on 5 successive days.
5-Fluril® admixtures or undiluted solutions in syringes are stable for 72 hours at room temperature.
Product should be stored below 25oC, without freezing and protected from light.
5-Fluril® 250 mg injection: Each box contains one vial of 10 mL solution containing 5-Flurouracil BP 250 mg.