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

    1 ampoule / vial contains: active substance: fluorouracil 250 mg

    Excipients: sodium hydroxide - 76.85 mg, water for injection - up to 5 ml

    Description:

    Transparent colorless or slightly yellowish liquid.

    Pharmacotherapeutic group: antitumour agent, antimetabolite
    ATX: & nbsp

    L.01.B.C.02   Fluorouracil

    Pharmacodynamics:

    Fluorouracil - antitumor (cytostatic) agent, antimetabolite of uracil. Fluorouracil breaks the synthesis of DNA and causes the formation of structurally deficient RNA, thereby inhibiting the division of tumor cells. The mechanism of action is due to the transformation of the drug into tissues into active metabolites 5-fluoro-2-deoxyuridine monophosphate and 5-fluorouridine tri-phosphate:

    - 5-fluoro-2-deoxyuridine monophosphate is a competitive inhibitor of the enzyme thymidylate synthetase, which is involved in the synthesis of deoxyribonucleic acid.

    - 5-Fluoruridine triphosphate is embedded in the cellular structure of ribonucleic acid (in the process of its synthesis) instead of uridip triphosphate, which leads to disruption of processing of ribonucleic acid and protein synthesis.

    Pharmacokinetics:

    After intravenous or intra-arterial administration, the drug is rapidly biotransformed and distributed in rapidly proliferating tissues, such as the stagnant brain, gastrointestinal mucosa and tumor tissues. Bioavailability of fluorouracil with intravenous administration is about 80%. The volume of distribution is 0.12 l / kg of body weight, the connection with plasma proteins is about 10%. 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 7-20 % of the drug is excreted by the kidneys unchanged for 6 hours (90% of this amount is excreted within the first hour) and 60-80% through the respiratory tract in the form of CO2,a small amount is excreted with bile. The renal clearance of fluorouracil is 170-180 ml / min.

    Indications:

    Cancer of the colon and rectum, breast cancer, esophageal cancer, stomach cancer, pancreatic cancer, primary liver cancer, ovarian cancer, cervical cancer, bladder cancer, head and neck cancer, prostate cancer, adrenal gland cancer, vulvar cancer, cancer of the penis, carcinoid

    Contraindications:

    • hypersensitivity to fluorouracil and / or other component of the drug;
    • pregnancy and the period of breastfeeding;
    • combination with inhibitors of dihydropyrimidine dehydrogenase (DPD) (brivudine, sorivudine);
    • severe leukopenia, neutropenia, thrombocytopenia; oppression of bone marrow hematopoiesis, active bleeding;
    • stomatitis, ulceration of the mucous membrane of the gastrointestinal tract, pseudomembranous enterocolitis;
    • acute severe infection (including Herpes Zoster, chickenpox);
    • severe renal dysfunction;
    • weakened patients;
    • postoperative period less than 30 days after extensive surgical intervention;
    • children's age (efficacy and safety not proven).

    Carefully:

    Renal and / or liver failure; acute infectious diseases of a viral, fungal or bacterial nature (including tuberculosis, chicken pox, shingles); infiltration of bone marrow by tumor cells; previously conducted intensive radiation therapy or chemotherapy.

    Pregnancy and lactation:

    In pregnancy, the use of fluorouracil is contraindicated. If you need to use the drug during lactation, breastfeeding should be discontinued.

    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 (the highest single dose of 1 g) once a week, 6-10 doses;

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

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

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

    Side effects:

    The incidence of side effects described below was determined according to the following gradation: very often (> 10%), often (> 1% and <10%), infrequently (> 0.1% and <1%), rarely (> 0.01% and <0.1%), very rarely (<0.01%).

    Allergic reactions

    infrequently - skin rash, dermatitis, urticaria, bronchospasm;

    rarely anaphylactic shock

    From the hematopoiesis:

    very often - leukopenia, neutropenia, myelosuppression, mostly dose-limiting;

    rarely - thrombocytopenia, anemia.

    The most significant decrease 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 - pancytopegy, agranulocytosis.

    From the immune system:

    very often - immunosuppression with an increase in the incidence of infectious diseases.

    The frequency is unknown - an increase in the blood concentrations of total thyroxine (T4) and total triiodothyronine (T3).


    From the digestive system:

    very often - anorexia, decreased appetite, inflammation and / or ulceration of the mucous membranes of the gastrointestinal tract (including stomatitis, pharyngitis, esophagitis, proctitis);

    often - diarrhea, nausea, vomiting, heartburn, taste change;

    infrequently - dehydration, bleeding from the gastrointestinal tract, impaired liver function, cholecystitis, mucositis, glossitis;

    Very rarely - damage to the liver cells, lethal necrosis of the liver.

    From the cardiovascular system:

    Very often - ischemic changes on the ECG, dilated cardiomyopathy;

    rarely - pain in the heart, arrhythmia, lowering blood pressure, myocarditis;

    very rarely - myocardial infarction, heart failure, angina, cardiomyalgia, cardiogenic shock, violation of peripheral cerebral circulation, Raynaud's syndrome, cardiac arrest, sudden death.

    Co side of the nervous system:

    often - transient reversible cerebral syndrome (ataxia, confusion, extrapyramidal motor and cortical disorders), drowsiness, impaired sensation, euphoria, nystagmus, retrobulbar neuritis, headache, disorientation, asthenia;

    infrequently - vertigo;

    very rarely - leukoencephalopathy, cerebral infarction (with combined therapy with mitomycin or cisplastin).

    From the sense organs

    rarely - conjunctivitis, excessive lacrimation due to stenosis of lacrimal ducts, photophobia, diplopia, cortical blindness (at high doses), visual impairment, mucous membrane damage, cataracts, optic neuritis, limitation of eye mobility, eyelid reversal.

    On the part of the reproductive system:

    infrequently - reversible oppression of the function of the sexual glands, leading to amenorrhea or azoospermia.

    From the skin and skin appendages:

    often - alopecia (reversible);

    infrequent - hyperpigmentation of the skin, depigmentation in the form of bands near the veins, dry and cracked skin, erythema, pruritus of skin, telangiectasia, photosensitization;

    rarely - changes in nails (onycholysis, pain and thickening of the nail bed, paronychia), convergence of nail plates, syndrome of palmar-plantar erythrodysesthesia (tingling in the hands and feet, followed by pain, hyperemia, swelling and flaking).

    Other:

    infrequently, weakness; "tides" of blood to the skin of the face, thrombophlebitis at the injection site, thromboembolism;

    rarely - fever, epistaxis, cough, shortness of breath, hyperuricemia, development of secondary infections, sepsis.

    Overdose:

    Symptoms: drowsiness, nausea, vomiting, diarrhea, ulcerative stomatitis and gastro-intestinal bleeding, suppression of bone marrow function (thrombocytopenia, leukopenia and agranulocytosis).

    Treatment: symptomatic. The specific antidote to fluorouracil is not known. It is possible to use the transfusion of leukocyte and platelet concentrates, it is necessary to control the electrolyte balance.

    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 long-term combined use with mitomycin,

    hemolytic-uremic syndrome.

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

    Thiazide diuretics can enhance myelosuppressive effects of fluorouracil.

    Levamisole significantly increases the degree of genes toxicity of fluorouracil.

    With the simultaneous use of fluorouracil and anthracyclines, cardiotoxic effectthe latter.

    With the simultaneous use of fluorouracil with phenytoin, the toxicity of the latter increases.

    The simultaneous use of fluorouracil with drugs that inhibit the enzyme dihydropyrimidine dehydrogenase, responsible for the catabolism of endogenous and fluorinated pyrimidines (brivudine, sorivudine) significantly increases the toxicity of fluorouracil. The interval between the use of brivudine, sorivudine or their analogues and fluorouracil should be at least 4 weeks.

    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 aminofenazop, fegylbutazone and sulfonamides.

    Chlordiazepoxide, disulfiram, griseofulvin and isopiaside can enhance the activity of fluorouracil.

    Metronidazole, cimetidine and allopuripol can increase the concentration of fluorouracil in the plasma, thereby increasing its toxic effects.

    In patients with breast cancer receiving therapy with cyclophosphamide, methotrexane, fluorouracil increases the risk of thromboembolic complications.When used in combination with radiotherapy fluorouracil can potentiate skin toxicity of the latter.

    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.

    With the simultaneous use of fluorouracil, calcium folinate and vinorelbine, the development of severe inflammation of the mucous membranes of the oral cavity and gastrointestinal tract is possible.

    Special instructions:

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

    When stomatitis, diarrhea, bleeding from the gastrointestinal tract appears, treatment with the drug should be stopped until these symptoms disappear.

    Care should be taken when prescribing to patients who have previously been exposed to high doses of radiation to the pelvic area or who received alkylating drugs.

    When fluorouracil is used, signs of cardiotoxicity may appear. Caution should be exercised in the treatment of patients experiencing chest pain during treatment or patients with a history of heart disease.

    When combined with oral anticoagulants should be carefully monitored blood clotting, prothrombin index.

    The period of treatment is necessary to control the total number of white blood cells, absolute neutrophil count, platelet count, to determine the hematocrit, hemoglobin, activity "liver" transaminases and bilirubin, inspect the mouth cavity of the patient for signs of stomatitis.

    With a significant reduction of body mass, decreased bone marrow function, impaired renal or hepatic function, in the early postoperative period (30 days) after extensive surgery initial dose should be reduced by 1/3 or ½.

    Due to the toxicity of FU when used in conjunction with drugs that suppress the enzyme dihydropyrimidine dehydrogenase (brivudine, sorivudin), before application of fluorouracil required break of not less than 4 weeks to restore the activity of endogenous and fluorinated pirimidipov.

    During the use of the drug, the use of live vaccines is contra-indicated, and contact with people newly vaccinated against poliomyelitis should be avoided. Men and women of childbearing age during treatment with fluorouracil and at least 3 months after should be taken reliable methods of contraception.

    Effect on the ability to drive transp. cf. and fur:

    Given the possible development of side effects, during the treatment with fluorouracil, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

    Form release / dosage:

    Solution for intravascular and intracavitary administration 50 mg / ml.


    Packaging:5 ml per 5 ml ampoule or 5 ml vials or 10 ml light-protective or brown glass.

    5 or 10 ampoules / bottles with a capacity of 5 ml are placed in a contour cell package. 1 circuit cell pack of 10 ampoules / bottles or 2 out-of-round packs of 5 ampoules / bottles with instructions for use are placed in a pack of cardboard.

    When packing the drug into ampoules, the pack is additionally inserted with an ampoule knife or scarifier. When using ampoules with a kink ring or with a notch and a point, the scarifier or knife of the ampoule ps is inserted.

    1 bottle with a capacity of 10 ml with the instruction for use is placed in an individual pack of cardboard.

    Storage conditions:

    In the dark place at a temperature of 15 to 25 ° C. Keep out of the reach of children. Do not freeze!

    Note. When storing the drug, precipitation may occur. In this case, the ampoule (vial) should be heated to a temperature of 60 ° C with vigorous shaking, after which the preparation must be cooled to a temperature of 35 ° C. If the precipitate dissolves and the solution becomes clear, the drug is usable.

    Shelf life:
    2 years.
    Do not use after the expiration date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-003127
    Date of registration:07.08.2015
    The owner of the registration certificate:Company DEKO, LLC Company DEKO, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspCompany DEKO, LLCCompany DEKO, LLC
    Information update date: & nbsp09.11.2015
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