Active substanceFluorouracilFluorouracil
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  • Dosage form: & nbspsolution for intravascular and intracavitary administration
    Composition:

    In 1 ml of solution contains: active substance: fluorouracil 50 mg

    Excipients: sodium hydroxide, hydrochloric acid diluted 1:20, water for injection

    Description:

    Transparent solution from colorless to pale yellow, free of visible particles.

    Pharmacotherapeutic group:antitumour agent, antimetabolite
    ATX: & nbsp

    L.01.B.C.02   Fluorouracil

    Pharmacodynamics:Fluorouracil is an antimetabolite of uracil. The mechanism of action is due to the transformation of the drug in tissues into an active metabolite, fluorourethidine monophosphate, which is a competitive inhibitor of the thymidylate synthetase enzyme involved in the synthesis of nucleic acids. Fluorouracil violates the synthesis of DNA and causes the formation of structurally deficient RNA, inhibiting the division of cancer cells. Active metabolites are localized within the cell,
    Pharmacokinetics:

    After intravenous administration, the preparation is rapidly biotransformed to an active metabolite of fluorouridine monophosphate and distributed in tumor tissues, intestinal mucosa, bone marrow, liver and other tissues. Easily penetrates the blood-brain barrier, getting into the cerebrospinal fluid and brain tissue. Metabolized mainly in the liver with the formation of inactive metabolites. The half-life of fluorouracil depends on the dose administered and is 8-22 minutes. About 20% of the drug is excreted by the kidneys unchanged for 6 hours (90% of this amount is excreted within 1 hour) and 60-80% through the respiratory tract in the form of CO2, a small amount is excreted with bile.

    Indications:
    • cancer of the colon and rectum;

    • mammary cancer;

    • esophageal carcinoma; stomach cancer;

    • pancreas cancer;

    • Primary liver cancer;

    • ovarian cancer;

    • cervical cancer;

    • cancer of the bladder;

    • malignant tumors of the head and neck;

    • prostate cancer;

    • adrenal cancer;

    • cancer of the vulva;

    • carcinoid.

    • cancer of the penis;


    Contraindications:

    • Hypersensitivity to fluorouracil and / or any other component of the drug.
    • Pregnancy and lactation.

    • Severe leukopenia, neutropenia, thrombocytopenia, stomatitis, ulceration of the gastrointestinal mucosa (GI tract), pseudomembranous enterocolitis.

    Carefully:

    renal and / or hepatic insufficiency, acute infectious diseases of viral, fungal or bacterial nature (including tuberculosis, chicken pox, shingles), bone marrow infiltration by tumor cells, previously intensive radiation therapy or chemotherapy.

    Dosing and Administration:

    Fluorouracil is included in many chemotherapy regimens, therefore, when choosing the route of administration, regimen and dosage in each individual case, one should be guided by the data of the special literature.

    The drug is injected intravenously or by slow infusion, intraarterially, intracavitary.

    The following doses and regimens are recommended:

    • 500 mg / m2 or 12-13.5 mg / kg daily for 3-5 days, the interval between courses is 4 weeks;

    • 600 mg / m2 or 15 mg / kg (highest single dose 1 g) once a week, 6-10 doses;

    • 600 mg / m2 on days 1 and 8 intravenously in combination with other cytostatics;

    • 1 g / m2 / day intravenously drip in the form of a constant infusion for 96-120 hours;

    When used in combination with calcium folinate, the dose of fluorouracil is usually reduced by 25-30%.
    Side effects:

    From the hematopoiesis: leukopenia, neutropenia, rarely - thrombocytopenia, anemia. The most significant drop in the number of leukocytes is usually observed from 9 to 14 days (up to 25 days), platelets - from 7 to 17 days of treatment. Very rarely, pancytopenia, agranulocytosis.

    From the digestive system: anorexia, nausea, vomiting, inflammation and / or ulceration of the mucous membranes of the gastrointestinal tract (including stomatitis), diarrhea, bleeding from the gastrointestinal tract, heartburn and taste change, glossitis, pharyngitis, esophagitis, mucositis, impaired liver function, cholecystitis.

    From the cardiovascular system: very rarely - pain in the heart, arrhythmias, myocardial ischemia, myocarditis, myocardial infarction, angina pectoris, heart failure, cardiomyopathy, cardiogenic shock, lowering blood pressure.

    From the nervous system: rarely - cerebellar ataxia, impaired sensitivity, disorientation, confusion, euphoria, nystagmus, retrobulbar neuritis, asthenia, headache.

    From the sense organs: conjunctivitis, irritation of the mucous membrane of the eyes, lacrimation due to stenosis of lacrimal ducts, photophobia, cataract, cortical blindness (at high doses), diplopia, visual impairment.

    On the part of the reproductive system: reversible oppression of the sexual glands, leading to amenorrhea or azoospermia.

    From the skin and skin appendages: alopecia, hyperpigmentation of the skin, dryness and skin cracks, telangiectasia, palmar-plantar erythrodysesthesia syndrome (tingling sensation in the hands and feet, followed by pain, hyperemia and swelling), change and convergence of nail plates (rarely), photosensitization.

    Allergic reactions: skin rash, dermatitis, urticaria, bronchospasm, anaphylactic shock (rarely).

    Other: "tide" of blood to the face, fever (rarely), thrombophlebitis at the injection site, epistaxis, cough, shortness of breath, hyperuricemia, weakness, development of secondary infections.

    Overdose:

    Signs and symptoms of an overdose include nausea, vomiting, diarrhea, ulcerative stomatitis and gastric bleeding, suppression of bone marrow function (thrombocytopenia, leukopenia and agranulocytosis). In case of an overdose monitor the function of hematopoietic patients for at least 4 weeks, if there are violations perform symptomatic therapy. The specific antidote to fluorouracil is not known.

    Interaction:

    Calcium folinate enhances the therapeutic and toxic effects of fluorouracil. .

    When used in combination with other cytostatics and interferon-alpha, there may also be an increase in both the antitumor effect and the toxicity of the fluorouracil.

    With prolonged joint use with mitomycin C, the appearance of hemolytic-uremic syndrome was observed.

    Simultaneous use of anticoagulants, coumarin derivatives, such as warfarin, can increase the anticoagulant effect.

    Thiazide diuretics can enhance the myelosuppressive effects of antitumor drugs.

    When used in combination with levamisole, the degree of hepatotoxicity significantly increases (an increase in the activity of alkaline phosphatase is often accompanied by an increase in serum transaminases or bilirubin).

    With the simultaneous reception with the drug sorivudine marked leukopenia, in some cases, led to death.

    Fluorouracil should not be used after and with therapy with aminophenazone, phenylbutazone and sulfonamides.

    Chlordiazepoxide, disulfiram, griseofulvin and isoniazid may enhance the activity of fluorouracil.

    In connection with the suppression of natural defense mechanisms in the treatment of fluorouracil, it is possible to intensify the replication of the vaccine virus or to reduce the production of antibodies in response to vaccine administration when vaccinated with live or inactivated vaccines, so the interval between the end of the drug application and vaccination with live or inactivated vaccines is from 3 months to 1 of the year.

    Special instructions:

    Fluorouracil is a cytotoxic drug, so care must be taken when handling it.

    When stomatitis or diarrhea occurs, the drug should be discontinued until the symptoms disappear.

    The initial dose should be reduced by 1/3 or 1/2 in the following cases: weight loss, postoperative period not less than 30 days after extensive surgery, insufficient bone marrow function, impaired liver or kidney function.

    Caution should be exercised in appointing patients who had previously been exposed to high doses of radiation to the pelvic area or who received alkylating preparations.

    During the treatment it is necessary to control the total number of leukocytes, the absolute number of neutrophils, platelets, to determine hematocrit, hemoglobin, the activity of "liver" transaminases and bilirubin concentration, to examine the oral cavity of the patient to identify signs of stomatitis.

    Men and women of childbearing age during treatment with fluorouracil and at least 3 months after should be taken reliable methods of contraception.

    In the case of precipitate formation under the influence of low temperatures, the solution should be heated to 60 ° C before use, shaking vigorously, and then cooled to room temperature.

    During the period of treatment it is necessary to refrain from driving the car and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

    Effect on the ability to drive transp. cf. and fur:During the period of treatment it is necessary to refrain from driving a car and practicing potentially dangerous activities,requiring increased concentration of attention and speed of psychomotor reactions.
    Form release / dosage:

    A solution for intravascular and intracavitary administration of 250 mg / 5 ml, 500 mg / 10 ml, 1000 mg / 20 ml and 5000 mg / 100 ml (50 mg / ml)


    Packaging:

    in bottles of colorless hydrolytic (class I) glass with a stopper of rubber chlorbutyl, an aluminum cap, equipped with a protective cap-insert made of colored polypropylene. The bottles are covered with a transparent film of polyethylene.

    1 bottle with instructions for use in a cardboard box.

    Storage conditions:

    In the dark place at a temperature of no higher than 15-25 ° C.

    Keep out of the reach of children.

    Shelf life:2 years

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N011626 / 01
    Date of registration:29.09.2008
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Information update date: & nbsp10.11.2015
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