Utoral

Each 10 mL vial contains Fluorouracil, USP 500 mg.

Pharmacology: Pharmacodynamics: Fluorouracil is an analogue of uracil, a component of ribonucleic acid. The drug is believed to function as an antimetabolite. After intracellular conversion to the active deoxynucleotide, it interferes with the synthesis of DNA by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase. Fluorouracil may also interfere with RNA synthesis.
Pharmacokinetics: After intravenous administration, Fluorouracil is distributed through the body water and disappears from the blood within 3 hours. It is preferentially taken up by actively dividing tissues and tumours after conversion to its nucleotide. Fluorouracil ready enters the C.S.F and brain tissue.
Following IV administration, the plasma elimination half-life averages about 16 minutes and is dose dependent. Following a single intravenous dose of Fluorouracil approximately 15% of the dose is excreted unchanged in the urine within 6 hours; over 90% of this is excreted in the first hour. The remainder is mostly metabolised in the liver by the usual body mechanisms for uracil.

Fluorouracil is used for the palliative treatment of carcinoma of the colon, rectum, breast, stomach, and pancreas that is not amenable to surgery or irradiation. The drug is also used as an adjunct to surgery for the treatment of various solid tumors. Fluorouracil is less effective in the treatment of carcinomas of the ovary, cervix, urinary bladder, liver, and pancreas, although improvements in some patients have been reported.

As a single agent, a usual dose by intravenous injection is 12 mg per kg body-weight daily (to a maximum of 0.8 to 1 g daily) for 3 or 4 days. If there is no evidence of toxicity, this may be followed after 1 day by 6 mg per kg on alternate days for 3 or 4 further doses. An alternative schedule is to give 15 mg per kg intravenously once a week throughout the course. The course may be repeated after 4 to 6 weeks or maintenance doses of 5 to 15 per kg (up to a maximum of 1 g) may be given weekly.
Fluorouracil may also be given by intravenous infusion, usual doses of 15 mg per kg daily (to a maximum of 1 g daily) being infused in 500 mL of 0.9% sodium chloride or 5% glucose injection over 4 hours and repeated on successive days until toxicity occurs or a total of 12 to 15 g has been given. Continuous infusion may also be used. The course may be repeated after 4 to 6 weeks. Fluorouracil has also been given by continuous intra-arterial infusion in doses of 5 to 7.5 mg per kg daily (regional perfusion).

The symptoms and signs of overdosage are dizziness, nystagmus, ataxia of extremity, dyslogia, and Parkinson's symptom may occur. If they occur, the administration should be discontinued and/or appropriate therapy should be utilized.

Patients who have the therapy of tegafur-gemestat-otastat potassium.
Patients who have less than 7 days of the finishing day of the therapy of tegafur-gemestat-otastat potassium.
Patients with a known hypersensitivity to fluorouracil.
Patients in a poor nutritional state, those with depressed bone marrow function, those with potentially serious infections.
Pregnant women, women who may become pregnant and nursing mother.
Patients with non-malignant tumor.

Use in patients with dihydropyrimidine dehydrogenase deficiency may cause toxicity; therefore the administration should be cautioned.
Because alternating therapy of methotrexate and fluorouracil is highly risky, the patients should be under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents.
Severe hepatic impairment including hepatitis may occur. Hepatic function tests should be monitored closely. If any symptoms occur, the administration should be discontinued and appropriate therapy instituted.

Patients who are in a poor nutritional state. Patients with severe surgical pus. Patients with hepatic impairment. Patients with heart disease or history of it.
General: The daily dose should not exceed 1 g.
In animal studies, Fluorouracil has been shown to be teratogenic. Therefore, it should not be administered to pregnant women or women suspected of being pregnant.
Severe enteritis (hemorrhagic, ischemic and necrotic enteritis) and dehydration may occur; it therefore, should be observed carefully. If severe abdominal pain or diarrhea occurs the administration should be discontinued and appropriate therapy instituted. If dehydration symptoms occur, appropriate therapy including liquor supplement should be initiated.
Use in Pregnancy & Lactation: The safety of this medicinal product for use in human pregnancy has not been established. UTORAL should, therefore, not be used during pregnancy.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and the potential for serious adverse reactions in nursing infants from UTORAL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The safety of this medicinal product for use in human pregnancy has not been established. UTORAL should, therefore, not be used during pregnancy.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and the potential for serious adverse reactions in nursing infants from UTORAL, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Psychoneura: Rarely, extrapyramidal symptom, facioplegia, dyslogia, ataxia, eye trembling, consciousness disorder, convulsion, disorientation, numbness of acra, leukoencephalopathy, parkinsonism may occur; therefore, the patients should be monitored sufficiently. If they occur, the administration should be discontinued. Malaise, and occasionally, dizziness may also occur.
Gastrointestinal Effect: Anorexia, nausea, vomiting and changing of taste can occur. Severe enteritis (hemorrhagic, ischemic, necrotic enteritis) may occur, therefore the patients should be sufficiently observed. If severe abdominalgia or diarrhea occurs, the administration should be discontinued and appropriate therapy instituted.
Cardiovascular: Congestive heart failure, cardiac infarction, angina, pain, ECG abnormalities, chest pain may occur. If any symptoms appear, the dose should be reduced or discontinued.
Hematologic: Pancytopenia, leukopenia, neutropenia, occasional cases of anemia, thrombocytopenia may occur. If any hematologic abnormality occurs, the administration should be discontinued and/or appropriate therapy instituted.
Hepatic: Rare case of severe hepatic disorder such as hepatitis may occur; therefore, liver function must be regularly tested.
Renal: Renal function and proteinuria have been reported.
Dehydration: If severe diarrhea or melena appears, the administration should be discontinued and/or appropriate therapy such as dehydration instituted.
Others: Stomatitis, systemic malaise, and occasionally alopecia may occur.

Various agents have been reported to biochemically modulate the anti-tumor efficacy or toxicity of Fluorouracil, common drugs include Methotrexate, Metronidazole, Tegafur, Leucovorin as well as Allopurinol and Cimetidine which can affect the availability of the active drug.

Dermal disorder such as erythema, blister, erosion, sore in arterial area, may be caused by intra-arterial injection and then it may develop musculus cutaneous sphacelism. If they occur, the administration should be discontinued and appropriate therapy instituted.
Hepatic intra-arterial administration may cause liver-biliary tract disorder (including cholecystitis, biliary necrotid).
If angioalgia and phlebitis occurred, administer slowly as possible.
When foreign substance is discovered by the naked eyes, medical product should not be used.

Store at a temperature not exceeding 30°C. Protect from light.

Cytotoxic Chemotherapy

L01BC02 - fluorouracil ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.

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