Active substanceFluorouracilFluorouracil
Similar drugsTo uncover
  • 5-Fluorouracil-Ebwe
    solution in / in c / cavity 
  • Fluorouracil
    solution c / cavity in / vessel. 
    FARM STANDART, OJSC     Russia
  • Fluorouracil-DECO
    solution c / cavity in / vessel. 
    Company DEKO, LLC     Russia
  • Fluorouracil-LENS®
    solution in / vessel. 
    LENS-PHARM, LLC     Russia
  • Fluorouracil-RONTS®
    solution c / cavity in / vessel. 
  • Ftoruracil-Teva
    solution c / cavity in / vessel. 
  • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    1 ml of the solution contains:

    Active substance: fluorouracil 50 mg.

    Excipients: sodium hydroxide - 14.7 mg, water for injection - 966.7 mg.

    Description:Transparent colorless or almost colorless solution.
    Pharmacotherapeutic group:Antitumor agent (antimetabolite)
    ATX: & nbsp

    L.01.B.C.02   Fluorouracil

    Pharmacodynamics:

    Fluorouracil is an 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 determined by its metabolic conversion to 5-fluoro-deoxyuridine-monophosphate and 5-fluorouridine tri-phosphate. 5-Fluoro-deoxyuridine-monophosphate is a competitive thymidine synthetase enzyme inhibitor,which leads to blocking the synthesis of deoxyribonucleic acid. It blocks the methylation reaction of deoxyuridic acid and its transformation into thymidyl acid, which leads to thymidine deficiency. Fluorouracil suppresses the synthesis of ribonucleic acid, by incorporating 5-fluorouridine triphosphate into its structure, instead of uridine triphosphate. This leads to a disruption in the processing of ribonucleic acid and protein synthesis.

    Fluorouracil has high myelotoxicity and gastrointestinal toxicity. Maximum Effectiveness observed in proliferative tissues (bone marrow, skin, mucous membrane). Unlike many antitumor drugs, it is effective for tumors of the gastrointestinal tract.

    Relatively highly toxic, especially violates the function bone marrow and gastrointestinal tract.

    Pharmacokinetics:

    After intravenous or intra-arterial administration fluorouracil rapidly biotransformed and distributed in rapidly proliferating tissues, such as bone marrow, 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 association with plasma proteins is approximately 10%. Easily penetrates the blood-brain barrier, getting into the cerebrospinal fluid and brain tissue. Metabolized mainly in the liver with the formation of an active metabolite - dihydro-5-fluorouracil, half-life which is much more than fluorouracil, and inactive metabolites. The half-life of fluorouracil depends on the administered dose and is 8-22 min. 3 hours after intravenous administration unchanged fluorouracil in the blood plasma is not detected. Fluorouracil is excreted mainly by light ones in the form of carbon dioxide (60-80%). 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). The renal clearance of fluorouracil is 170-180 ml / min. An insignificant amount of fluorouracil is excreted with bile.

    Indications:

    Monotherapy or in combination with other antineoplastic agents for cancer of the colon and rectum, breast cancer, esophagus cancer, stomach cancer, pancreatic cancer, primary liver cancer,ovarian cancer, cervical cancer, bladder cancer, malignant head and neck tumors, prostate cancer, adrenal cancer, penile cancer, vulvar cancer, carcinoid tumors.

    Contraindications:

    hypersensitivity to fluorouracil and / or any other component of the drug;

    expressed leukopenia, neutropenia, thrombocytopenia, hematopoiesis;

    active bleeding;

    stomatitis, ulceration of the oral mucosa and gastrointestinal tract;

    pseudomembranous enterocolitis;

    acute severe infection (including Herpes Zoster, chicken pox);

    marked violation of liver function;

    severe renal dysfunction;

    pregnancy;

    the period of breastfeeding;

    childhood;

    combination with inhibitors of dihydropyrimidine dehydrogenase (brivudine, sorivudine),

    insufficiency of dihydropyrimidine dehydrogenase;

    weakened patients.

    Carefully:With caution, the drug is used in patients with renal insufficiency; hepatic insufficiency; acute infectious diseases of viral, fungal or bacterial nature (incl.tuberculosis, chicken pox, shingles); cardiovascular diseases in the anamnesis; infiltration of bone marrow by tumor cells, previously conducted by radiation therapy or chemotherapy.
    Pregnancy and lactation:

    5-fluorouracil belongs to the category D.

    Controlled studies on the use of 5-fluorouracil in pregnant women do not, however, based on the pharmacological and toxicological characteristics of 5-fluorouracil, it can be assumed that when prescribing to pregnant women 5- fluorouracil can have a damaging effect on the fetus. In studies of reproductive performance in animals, the administration of 5-fluorouracil was accompanied by an increase in embryo death and teratogenic effects, which is the expected effect of fluoropyrimidine derivatives. 5-fluorouracil should be considered a potential teratogen for humans. During pregnancy, 5-fluorouracil should not be used. If 5-fluorouracil is prescribed during pregnancy or if the pregnancy occurs in a patient already taking this drug, it should be warned of a possible hazard to the fetus.Women of reproductive age should be treated with 5-fluorouracil only if reliable contraception is used.

    It is not known whether 5-fluorouracil and its metabolites are excreted in breast milk. Since many drugs are ingested in human milk, and also because of possible severe adverse reactions in infants, the administration of 5-fluorouracil to a nursing mother should be avoided, or during the period of treatment, breastfeeding should be stopped.

    Dosing and Administration:

    The dose and scheme of therapy are determined individually depending on the condition of the patient and the type of cancer, and also whether 5-fluorouracil is used in the form of monotherapy or in combination with other drugs. Start treatment is necessary in a hospital. The drug is injected intravenously or by slow infusion, intraarterially, intracavitary.

    The daily dose of 5-fluorouracil should not exceed 1 g.

    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 on days 1 and 8 intravenously in combinations 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:

    According to the World Health Organization (WHO), adverse reactions are classified according to this developmental frequency as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

    On the part of the blood system and lymphatic system very often: myelosuppression (dose-limiting), neutropenia, thrombocytopenia, leukopenia, agranulocytosis, anemia, pancytopenia. 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.

    On the part of the immune system very often: immunosuppression with an increase in the incidence of infectious diseases; rarely: generalized allergic reactions, anaphylactic shock; frequency unknown: development of secondary infections, sepsis.

    Endocrine disorders frequency is unknown: an increase in the total thyroxine (T4) and triiodothyronine (T3) in blood plasma,without increasing the content of free T4 and thyroid-stimulating hormone (TSH) and without clinical signs of hyperthyroidism.

    From the side of nutrition and metabolism very often: hyperuricemia.

    From the side of the nervous system infrequently: nystagmus, headache, vertigo, transient reversible cerebral syndrome (ataxia, confusion, extrapyramidal motor and cortical disorder), drowsiness, euphoria, optic neuritis; very rarely leukoencephalopathy with symptoms such as ataxia, speech impairment, disorientation, myasthenia gravis, aphasia, convulsions, coma (field application fluorouracil in high doses or in patients with deficiency dihydropyrimidine dehydrogenase), cerebral infarction (prikombinirovannoy therapy with mitomycin or tsisplastinom) .

    From the senses Uncommon: conjunctivitis, excessive lacrimation duct stenosis, blepharitis, ectropion, photophobia, optic neuritis, ocular motility restriction (s), visual disturbances, cortical blindness (at high doses)

    From the side of the cardiovascular system very often: ischemic changes on the ECG; often: pain in the heart; infrequently: arrhythmias,ischemia, myocardial infarction, myocarditis, dilated cardiomyopathy, lowering of arterial pressure, cardiogenic shock, heart failure; rarely: violation of peripheral, cerebral circulation, Raynaud's syndrome, thrombophlebitis, thromboembolism; very rarely: angina pectoris, cardiac arrest, sudden cardiac death.

    From the respiratory, thoracic and mediastinal organs very often: nosebleeds, bronchospasm, cough, shortness of breath.

    From the digestive system very often: decreased appetite, inflammation and / or ulceration of the mucous membrane of the gastrointestinal tract (including stomatitis, esophagitis, pharyngitis, proctitis), diarrhea, nausea, vomiting, anorexia; infrequently: dehydration, bleeding from the gastrointestinal tract, damage to liver cells, impaired liver function; very rarely: cholecystitis, liver necrosis (including fatal); frequency unknown: heartburn, taste change.

    From the genitourinary system is infrequent: renal failure, reversible suppression of the function of the sexual glands, leading to amenorrhea or azoospermia.

    From the skin and subcutaneous tissues very often: alopecia (reversible), syndrome palmar-plantar erythrodesisia (sensation of tingling in the hands and feet with the subsequent appearance of pain, flushing, swelling and flaking of the skin); infrequent: hyperpigmentation or depigmentation of the skin in the form of bands near the veins, dry skin, skin cracks, erythema, pruritus, rashes, telangiectasias, changes (onycholysis, pain and thickening of the nail bed, paronychia) and nail plate convergence (rarely), photosensitivity;

    General disorders and disorders at the injection site are very common: increased fatigue, fever, weakness; frequency unknown: thrombophlebitis at the site of administration.

    Overdose:

    Symptoms: nausea, vomiting, diarrhea, ulcerative stomatitis and gastrointestinal bleeding, oppression of function bone marrow (thrombocytopenia, leukopenia and agranulocytosis).

    Treatment: symptomatic.

    The specific antidote to fluorouracil is not known. It is possible to use transfusion of leukocyte and platelet concentrates, antibacterial therapy, it is necessary to adjust the water-electrolyte balance.

    Monitoring of clinical blood analysis is necessary to be carried out regularly for 4 weeks after an overdose of the drug.

    Interaction:

    Calcium folinate enhances the therapeutic and toxic effects of fluorouracil. Severe diarrhea, sometimes fatal, can occur as a clinical manifestation of this interaction. The most common complication with fatal outcome occurred when 600 mg / m2 fluorouracil intravenously bolus once a week, in combination with calcium folinate.

    Use in combination with other cytostatics and interferon-alpha can also be observed to enhance both the antitumor effect and the toxicity of fluorouracil.

    When used in combination with radiotherapy fluorouracil can potentiate skin toxicity first.

    At long joint application with mitomycin the appearance of a hemolytic uremic syndrome was observed.

    With combined therapy in combination with other drugs that depress the function of the bone marrow, correction of the dose of fluorouracil is required.

    At simultaneous the use of fluorouracil and anthracyclines may exacerbate the cardiotoxic effect of the latter.

    When used simultaneously with enzyme inhibitors dihydropyrimidine dehydrogenase, responsible for the catabolism of endogenous and fluorinated pyrimidines (brivudine, sorivudine), the toxicity of fluorouracil significantly increases. Therefore, the interval between the use of fluorouracil and brivudine, sorivudine or their analogues should be at least 4 weeks. If necessary, before the start of therapy, it is recommended to determine the activity of the enzyme dihydropyrimidine dehydrogenase.

    With the simultaneous use of phenytoin and fluorouracil, the plasma concentration of phenytoin increases, which can lead to symptoms of intoxication. Fluorouracil should not be used after and with therapy with aminophenazone, phenylbutazone and sulfonamide.

    Chlordiazepoxide, disulfiram, griseofulvin and isoniazid may enhance the activity of fluorouracil. Fluorouracil may reduce the immunological response to vaccination. The use of live vaccines during treatment fluorouracil om may lead to increased replication of the virus. Levamisole can enhance the hepatotoxicity of fluorouracil.There are reports of a decrease in the time of blood coagulation in Kwiku with simultaneous use of warfarin and fluorouracil, and also in combination with levamisole. Metronidazole and cimetidine can increase the concentration of fluorouracil in the blood plasma, thereby increasing its toxic effects.

    Thiazide diuretics can enhance myelotoxicity of fluorouracil.

    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, including fatal outcome, is possible.

    In patients with breast cancer receiving combination therapy with cyclophosphamide, methotrexate, fluorouracil and tamoxifen increase the risk of thromboembolic complications.

    When using fluorouracil, false-positive results are possible in the determination of bilirubin and 5-hydroxyindole of acetic acid in the urine.

    Special instructions:

    Treatment with the drug 5-fluorouracil-Ebwee should be carried out under the supervision of an oncologist, who has experience in the use of antimetabolites. Taking into account the risk of developing severe toxic reactions, including fatalities, the doctor is obliged to inform the patient in detail about the possible risk and necessary safety measures.Start treatment is necessary in a hospital.

    Before using the 5-fluorouracil-Ebweave solution in the case of precipitate formation under the influence of low temperatures, the solution should be heated to 60 ° C, vigorously shaking, and then cooled to room temperature. If the sediment does not dissolve, the product must be disposed of in accordance with the regulations in force for the destruction of hazardous waste.

    With adequately selected therapy with 5-fluorouracil-Ebwee, leukopenia usually develops. The minimum number of leukocytes is usually observed between 7-14 days of the first course of therapy, but sometimes this minimum can be observed after 20 days, which returns to the norm by the 30th day of therapy. During the treatment with 5-fluorouracil-Ebweve, a clinical blood test should be performed at least once a week.

    When stomatitis, diarrhea, bleeding from the gastrointestinal tract or any other localization occurs, the drug should be discontinued until these symptoms disappear. With diarrhea of ​​mild severity, it may be sufficient to use only antidiarrheal agents.

    With a significant reduction in body weight, decreased bone marrow function, impaired liver function or kidney, in the early postoperative period (up to 30 days) after extensive surgical The initial dose should be reduced by 1/3 or 1/2.

    Caution should be exercised when used in patients previously exposed to high doses of radiation to the pelvic area or who received alkylating drugs.

    Since concomitantly with the enzyme inhibitors dihydropyrimidine dehydrogenase (brivudine, sorivudine) significantly toxicity of fluorouracil, a break before with the preparation of 5-fluorouracil-Ebove to restore the activity of endogenous and fluorinated pyrimidines, at least 4 weeks. With the use of 5-fluorouracil-Ebwee, there may be signs of cardiotoxicity. Caution should be exercised in the treatment of patients experiencing chest pain during treatment courses or patients with a history of heart disease.

    Before and during therapy with 5-fluorouracil-Ebweave, it is recommended that:

    daily examination of the mucous membrane of the mouth and throat;

    perform a clinical blood test with the calculation of blood cells before each use of the drug;

    correct the water-electrolyte balance;

    evaluate liver function (activity "hepatic" enzymes).

    When fluorouracil and oral anticoagulants are used concomitantly, blood coagulability (for example, a prothrombin index) should be closely monitored.

    During the period of 5-fluorouracil-Ebwee preparation use of live vaccines is contra-indicated, and contact with people newly vaccinated against poliomyelitis should be avoided.

    Men and women of childbearing age should be treated with reliable methods of contraception during treatment with 5-fluorouracil-Ebweave and at least 3 months after.

    Due to fluorouracil has mutagenic and carcinogenic properties, dilute the drug should be in aseptic conditions in a specially designated room. This should be handled by trained personnel. It is necessary to take all measures to prevent the fluorouracil solution from getting on the skin and mucous membranes, in particular to wear protective clothing (gown, cap, mask, glasses and disposable gloves).If fluorouracil enters the skin or mucous membranes, rinse thoroughly with soap and water or (eyes) with plenty of water. Pregnant personnel should be removed from work with fluorouracil.

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

    Because of the likelihood of side effects such as drowsiness, headache and confusion, care should be taken when practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions.

    Form release / dosage:Concentrate for the preparation of a solution for infusions of 50 mg / ml.
    Packaging:

    5 ml or 10 ml in colorless glass ampoules (type 1, Hebrew F.)

    5 ampoules are placed in an open or closed blister of G1VX.

    1 blister together with instructions for use are placed in a cardboard box.

    5 ml, 10 ml, 20 ml or 100 ml in bottles of brown glass (type 1, Hebrew F), sealed with rubber stoppers, under an aluminum run-off, covered with protective Teflon lids.

    1 bottle together with the instruction for use is placed in a cardboard box.
    Storage conditions:

    Store in a dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Special precautions for the destruction of unused medications

    Remains of the preparation and all tools and materials used to prepare solutions for 5-fluorouracil-Ebweze infusions should be disposed of in accordance with the standard hospital procedure for the disposal of cytotoxic substances, taking into account existing regulations for the destruction of hazardous waste.


    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 N015232 / 01
    Date of registration:11.09.2008
    The owner of the registration certificate:Ebewe Pharma Gesmb.b. Nfg. KGEbewe Pharma Gesmb.b. Nfg. KG Austria
    Manufacturer: & nbsp
    Representation: & nbspSANDOZ SANDOZ Switzerland
    Information update date: & nbsp08.07.2014
    Illustrated instructions
      Instructions
      Up