5-Fluril

5-Fluril is indicated, alone or in combination, for the treatment of

• Carcinoma of the colon or rectum
• Carcinoma of the stomach and exocrine pancreas
• Carcinoma of the liver
• Carcinoma of the breast
• Carcinoma of the bladder
• Carcinoma of the lung
• Epithelial ovarian carcinoma
• Cervical carcinoma

Intravenous administration

Fluorouracil may be given either as a rapid intravenous bolus injection directly into a peripheral vein, or as a slow intravenous infusion diluted in 500 ml of 5% Dextrose solution and infused over 2–3 hours on 5 successive days. The most common bolus schedule is 12–13.5 mg/kg (500 mg/m²) daily for 5 days, repeated at 4-weekly intervals.

Palliative management of cancer

Initial dose: 12 mg/kg intravenously once daily for 4 successive days. Maximum dose: 800 mg/day. If no toxicity is observed, 6 mg/kg may be given on days 6, 8, 10, and 12 (no therapy on days 5, 7, 9, or 11). Discontinue at the end of day 12 even if no toxicity has appeared.

Poor-risk patients and those in an inadequate nutritional state

Initial dose: 6 mg/kg/day for 3 days. Maximum dose: 400 mg/day. If no toxicity is observed, 3 mg/kg may be given on days 5, 7, and 9 (no therapy on days 4, 6, or 8). Discontinue at the end of day 9 even if no toxicity has appeared.

Maintenance therapy

Where toxicity has not been a problem, maintenance may be continued using either of the following schedules:

• Repeat the first-course dosage every 30 days after the last day of the previous course, or
• Once toxic signs from the initial course have resolved, give a maintenance dose of 10–15 mg/kg/week as a single dose. Maximum dose: 1 g/week.

The patient's response to the previous course should always be considered and doses adjusted accordingly.

Cervical cancer (usual adult dose)

In combination with cisplatin: 1 g/m² IV on day 1. The cycle is repeated every 21 days.

Malignant disease in children

The manufacturer has not established the safety and effectiveness of fluorouracil in children. Where it has been used in children, adult guidelines have been followed.

Intra-arterial infusion

For adults, 5–7.5 mg/kg body weight is dissolved in 20–100 ml of 5% Dextrose solution and administered over 10–20 days using an infusion pump.

Combination with radiation

A usual adult daily dose of 5–10 mg/kg body weight is given in combination with radiation, using either the systemic administration method or intra-arterial infusion.

Combination with other anticancer drugs

Fluorouracil is used alone or in combination for the adjuvant treatment of breast and gastrointestinal cancers, and for palliation of inoperable malignant neoplasms — particularly those of the gastrointestinal tract, breast, head and neck, liver, genitourinary system, and pancreas. It is also used with cyclophosphamide and methotrexate in combination chemotherapy for breast cancer. A usual adult dose of 5–10 mg/kg body weight daily is given with other anticancer drugs, either every day or intermittently once to twice weekly, by systemic administration or intra-arterial infusion.

Fluorouracil may be administered as a rapid intravenous bolus injection directly into a peripheral vein, or as a slow intravenous infusion.

Bolus injection

The vial contents are injected directly into a peripheral vein. The most common schedule is 12–13.5 mg/kg (500 mg/m²) daily for 5 days, repeated at 4-weekly intervals.

Slow intravenous infusion

1. Dilute the required dose in 500 ml of 5% Dextrose solution.
2. Infuse over 2–3 hours on each of 5 successive days.

Palliative management of cancer

Initial dose: 12 mg/kg IV once daily for 4 successive days. Maximum dose: 800 mg/day. If no toxicity occurs, 6 mg/kg may be given on days 6, 8, 10, and 12 (no therapy on days 5, 7, 9, or 11). Discontinue at the end of day 12 even if no toxicity has appeared.

Poor-risk patients and those in an inadequate nutritional state

Initial dose: 6 mg/kg/day for 3 days. Maximum dose: 400 mg/day. If no toxicity occurs, 3 mg/kg may be given on days 5, 7, and 9 (no therapy on days 4, 6, or 8). Discontinue at the end of day 9 even if no toxicity has appeared.

Maintenance therapy

Where toxicity has not been a problem, continue with one of the following

• Repeat the first-course dosage every 30 days after the last day of the previous course, or
• Once toxic signs have resolved, give 10–15 mg/kg/week as a single dose. Maximum dose: 1 g/week.

Cervical cancer (usual adult dose)

In combination with cisplatin: 1 g/m² IV on day 1, repeated every 21 days.

Malignant disease in children

Safety and effectiveness have not been established. Where used, adult guidelines have been followed.

Intra-arterial infusion

For adults, 5–7.5 mg/kg body weight is dissolved in 20–100 ml of 5% Dextrose solution and administered over 10–20 days using an infusion pump.

Combination with radiation

A usual adult daily dose of 5–10 mg/kg body weight is given in combination with radiation, by systemic administration or intra-arterial infusion.

Combination with other anticancer drugs

A usual adult dose of 5–10 mg/kg body weight daily is given with other anticancer drugs — every day or intermittently once to twice weekly — by systemic administration or intra-arterial infusion. Fluorouracil is also used with cyclophosphamide and methotrexate in combination chemotherapy for breast cancer.

Fluorouracil is inactive in mammalian cells in its unchanged form, but is converted into the active metabolite 5-fluorodeoxyuridine monophosphate (FdUMP) through a variety of metabolic pathways. Its primary mechanism is the inhibition of the enzyme thymidylate kinase, which reduces the formation of thymidine and consequently of DNA.

The active metabolite FdUMP forms a stable complex with the folate cofactor N-5,10-methylene tetrahydrofolate, thereby inactivating thymidylate kinase. Fluorouracil (as FdUMP) is also incorporated into RNA, resulting in fluorination of RNA.

The cytotoxic effect of fluorouracil is directed mainly at cells in the proliferative phase. Cells in the G2 and S phases are most affected, although some effect may occur at any stage of the cell cycle.

Potentially life-threatening effects

Severe adverse effects from fluorouracil are related to the dosage and duration of therapy.

Cardiac effects

Occasional case reports have associated fluorouracil therapy with ischemic cardiac events. In several cases, cardiotoxicity occurred within a few hours of the first dose.

Hematological effects

Potentially lethal hematological toxicity may develop within the first 10 days of treatment but generally resolves within 3 weeks. At recommended doses and schedules, severe hematological toxicity is uncommon. Extensive prior irradiation or concomitant use of cytotoxic drugs tends to worsen the severity of hematological side effects.

Neurological effects

Central nervous system effects have been occasionally reported. Cerebral ataxia is dose-dependent, with an incidence of 3.1–7%. Acute cerebellar syndromes and myelopathy have been described following intrathecal administration. Neurological syndromes may rarely occur after carotid artery perfusion in head and neck cancer.

Other serious effects

• Allergic reactions (including difficulty breathing, throat closing, swelling of the lips, tongue, or face, or hives)
• Decreased bone marrow function and blood problems (extreme fatigue, easy bruising or bleeding, black/bloody/tarry stools, or fever, chills, or signs of infection)
• Hand-foot syndrome (tingling, pain, redness, swelling, or tenderness of the hands and feet)
• Severe vomiting, diarrhoea, frequent or watery bowel movements
• Sores in the mouth or throat
• Stomach pain, heartburn, or black/bloody/tarry stools

Less serious side effects

• Mild to moderate nausea, vomiting, or loss of appetite
• Balance problems
• Confusion
• Rash and itching
• Temporary hair loss

Eye effects

Conjunctivitis — both acute and chronic — can progress to tear duct stenosis and ectropion following prolonged administration. Very prolonged low-dose administration (beyond 3 months) is associated with low systemic toxicity but may include painful and tender hands and feet with erythema of the extremities.

Fluorouracil is contraindicated in

• Severely debilitated patients
• Patients with bone marrow suppression resulting from radiotherapy or chemotherapy
• Pregnant or breastfeeding women
• Patients who do not have a malignant illness

Fluorouracil is a highly toxic drug with a narrow margin of safety. Patients must be carefully supervised, as a therapeutic response is unlikely without some evidence of toxicity. The daily dose must not exceed 1 gram.

Treatment should be discontinued promptly if any of the following signs of toxicity appear:

• Leucopenia (WBC below 3,500/mm³)
• Thrombocytopenia (platelet count below 100,000/mm³)
• Stomatitis (the first small ulceration at the inner margin of the lips is a signal to stop treatment)
• Severe diarrhoea (frequent bowel movements or watery stools)
• Gastrointestinal ulceration and bleeding

Neonates

No dosage recommendations are established for neonates.

Children

Safety and effectiveness in children have not been established.

Elderly patients

No special precautions are required. Doses should be adjusted according to the patient's weight and height.

Pregnancy

Fluorouracil is contraindicated throughout pregnancy. The risk of teratogenesis decreases as pregnancy advances, but fluorouracil used in the first trimester has been reported to cause multiple congenital abnormalities. Most cytotoxic drugs, including fluorouracil, are absolutely contraindicated during the first trimester. There are case reports of pregnancy being conducted successfully when combination chemotherapy was given to the mother during the second and third trimesters, but further data on the long-term development of neonates are required before any of these compounds can be considered free of late effects.

Breastfeeding

It is not known whether fluorouracil is excreted in human milk. Because fluorouracil inhibits DNA, RNA, and protein synthesis, mothers should not breastfeed while receiving this drug.

Deliberate overdose cases are not documented, but excessive toxicity may occur due to hematological effects. There is no specific antidote to fluorouracil toxicity; treatment is supportive. In addition to hematological toxicity, other toxicities will occur with overdose. Signs and symptoms are qualitatively similar to the known side effects. Treatment should be initiated promptly and appropriate drugs given to control symptoms.

Pre-treatment with cimetidine for 4 weeks was found to increase plasma concentrations of fluorouracil following both intravenous and oral administration in 6 patients. This effect was attributed to a combination of hepatic enzyme inhibition and reduced hepatic blood flow.

Store the vial in its original carton at a temperature not exceeding 25°C. Do not refrigerate. Protect from light.

What is the price of 5-Fluril 25 mg/ml in Bangladesh (BD)?

5-Fluril 25 mg/ml price in Bangladesh is ৳70 per vial. Prices may vary by pharmacy and are updated regularly on this page.

What is 5-Fluril used for?

5-Fluril is indicated, alone or in combination, for the treatment of: - Carcinoma of the colon or rectum - Carcinoma of the stomach and exocrine pancreas - Carcinoma of the liver - Carcinoma of the breast - Carcinoma…

Is 5-Fluril an antibiotic?

No, 5-Fluril is not an antibiotic.