Active substanceVinorelbineVinorelbine
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  • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    In 1 ml of the concentrate contains:

    active substance: vinorelbine ditartrate 13.85 mg, equivalent to vinorelbine - 10 mg; auxiliary substance: water for injection - up to 1 ml.

    Description:

    Transparent colorless or slightly colored liquid.

    Pharmacotherapeutic group:Antitumor agent, alkaloid
    ATX: & nbsp

    L.01.C.A.04   Vinorelbine

    Pharmacodynamics:

    Vinorelbine (pink vinca alkaloid, obtained semi-synthetically) is an antitumor agent from the group of vinca alkaloids. Disrupts the polymerization of tubulin in phases G2 and M of the cell cycle. It blocks mitosis, causes destruction of cells in the interphase or subsequent mitosis. Acts mainly on mitotic microtubules; when high doses are applied, it also affects axonal microtubules. The effect of spiral tubulin, caused by vinorelbine, is less pronounced than that of vincristine.

    Pharmacokinetics:

    After intravenous administration of the preparation, three-phase kinetics can be traced. The average half-life in the final phase is 40 (27.7-43.6) hours. The connection with plasma proteins is 79.6-91.2%. Intensively binds to platelets, lymphocytes, alpha 1-acid glycoprotein, albumin and lipoproteins. It penetrates well into tissues and lingers in them for a long time. Large quantities are defined in; spleen, liver, kidneys, lungs and thymus, moderate - in the heart and muscles, minimal - in adipose tissue, head and bone marrow. Concentration in the lungs is 300 times higher than the concentration in the plasma. Forms a number of metabolites; one of the metabolites, diacetylvinorelbine, retains antitumor activity. Metabolised in the liver. It is excreted mainly with bile.

    Indications:

    - Common inoperable non-small cell lung cancer;

    - common breast cancer, refractory or progressive after chemotherapy, including anthracyclines.

    Contraindications:

    - Hypersensitivity to vinaalkaloids; severe liver dysfunction;

    - severe infectious diseases during the initiation of therapy or transferred during the last 2 weeks;

    - initial neutrophil count <1500 cells / μl of blood and platelets <75,000 cells / μl of blood;

    - radiation therapy of the hepatobiliary region;

    - pregnancy and lactation;

    - Children's age (data on use in children is not enough).

    Carefully:

    Respiratory failure, oppression of bone marrow hematopoiesis (including after previous chemotherapy or radiation treatment), constipation or intestinal obstruction in the history, neuropathy in the anamnesis; simultaneous reception of inhibitors of isoenzyme CYP3A4.

    Pregnancy and lactation:

    The drug is contraindicated during pregnancy and breastfeeding. During and for at least three months after discontinuation of therapy, patients need to use reliable contraceptive methods.

    Dosing and Administration:

    Vinorelbine is used as a form of monotherapy, and in combination with other antitumor drugs. When choosing a dose and mode of administration in each individual case, you should refer to the special literature.

    Vinorelbine is administered strictly intravenously in the form of 6-10 intravenous bolus injection or 20-30 minute infusion.

    In the monotherapy regime, the usual dose of the drug is 25-30 mg / m2 body surface once a week. The drug is diluted in 0.9% solution of sodium chloride or 5% solution dextrose to a concentration of 1.5-3.0 mg / ml. After the introduction of the drug, the vein should be washed by additionally adding at least 250 ml of a 0.9% solution of sodium chloride.

    Correction of dosing regimen of vinorelbine depending on hematological parameters:

    Number of neutrophils on the day of drug administration (cells / μl)

    Percentage of starting dose of vinorelbine

    ≥ 1500

    100%

    1499-1000

    50%

    < 1000

    The drug is not administered. Repeat the determination of the number of neutrophils after 1 week. If due to granulocytopenia had to refrain from 3 weekly injections of the drug, the use of vinorelbine is recommended to stop

    In patients with hyperthermia and / or sepsis against the background of granulocytopenia during treatmentor when two weekly injections of the drug are missed in a row, due to the low number of neutrophils, the doses in subsequent administrations should be as a percentage of the previous doses:

    ≥ 1500

    75%

    1499-1000

    37,5 %

    <1000

    the drug is not administered.

    Correction of dosing regimen of vinorelbine in liver failure: patients with hepatic insufficiency vinorelbine should be administered with caution, when hyperbilirubinemia occurs against the background of treatment with vinorelbine, subsequent doses should be reduced according to the following recommendations:

    Concentration of total bilirubin (μmol / L)

    Percentage of starting dose of vinorelbine

    ≤34,2

    100%

    35,9,51,3

    50%

    >51,3

    25%

    For patients with a body surface area> 2 m2 a single dose of vinorelbine should not exceed 60 mg.

    Children: the safety and efficacy of vinorelbine in children have not been studied.

    Aged people: There are no specific instructions for the use of vinorelbin in the elderly.

    Side effects:

    The following side effects were more common than in isolated cases. The following criteria were used to estimate the incidence of adverse events: very often (> 1/10); often (> 1 / 100.1 / 10); sometimes (> 1/1000, 1/100); rarely (> 1/10 j000, 1/1000); extremely rare (1/10 000).

    On the part of the hematopoiesis system: very often - neutropenia, anemia, thrombocytopenia, the attachment of secondary infections against the background of oppression of bone marrow hematopoiesis; often - a fever (38 ° C) against neutropenia; sometimes - sepsis, septicemia; extremely rare - complicated septicemia, in some cases leading to death. The smallest number of neutrophils is observed at 7-10 day from the beginning of therapy, recovery occurs in the next 5-7 days.

    Cumulation of hematotoxicity was not observed.

    From the side of the peripheral nervous system: very often - paresthesia, hyperesthesia, reduction or loss of deep tendon reflexes; often - weakness in the legs; sometimes - severe paresthesia with sensory and motor symptoms, usually reversible.

    From the side of the cardiovascular system: sometimes - increase or decrease in blood pressure (BP), "flushes" of blood to the face and cold extremities; rarely - ischemic heart disease (IHD) (angina pectoris, myocardial infarction), severe hypotension, collapse; very rarely - tachycardia, palpitation, violation heart rate.

    From the respiratory system: sometimes - shortness of breath, bronchospasm; rarely - interstitial pneumonia (with combination therapy with synthomycin), acute respiratory distress syndrome.

    From the digestive system: very often - nausea, vomiting, stomatitis, constipation, diarrhea, transient increase in the activity of "liver" transaminases; rarely - pancreatitis, increased bilirubin level, intestinal paresis,

    From the immune system: rarely anaphylactic shock, angioedema edema.

    From the skin and skin appendages: often - alopecia; rarely - skin rashes.

    Local reactions: often - pain / burning or redness at the injection site, change in vein color, phlebitis; when extravasation - inflammation of subcutaneous fat; possibly - necrosis of surrounding tissues.

    Other: often - increased fatigue, myalgia, arthralgia, fever, pains of different localization, including pain in the chest, pain in the lower jaw and in the area of ​​tumor formations; rarely - hyponatremia; very rarely - hemorrhagic cystitis and the syndrome of inadequate secretion of ADH.

    Overdose:

    The specific antidote is not known. In case of an overdose, the patient should be hospitalized and closely monitor the functions of vital organs.The main expected overdose manifestations include suppression of bone marrow function and peripheral neuropathy. Treatment is symptomatic.

    Interaction:

    When combined with mitomycin C, acute respiratory failure may develop.

    When combined with paclitaxel, the risk of neurotoxicity increases.

    When used in conjunction with cisplatin, granulocytopenia is increased.

    Application on the background of radiation therapy leads to radiosensitization.

    The drug should be used with caution with cytochrome P450-3A inhibitors.

    Special instructions:

    Treatment vinorelbine should be conducted under the supervision of a doctor who has experience with antitumor drugs.

    Treatment vinorelbine conducted under strict hematological control, determining the number of leukocytes, neutrophils and hemoglobin level before each next injection.

    If the liver function is impaired, vinorelbine should be reduced.

    If there is a violation of the kidneys, it is necessary to monitor the patient more closely.

    When there are signs of neurotoxicity, treatment with the drug should be discarded.

    When there is shortness of breath, coughing or hypoxia of unexplained etiology, the patient should be examined to exclude pulmonary toxicity.

    When extravasation, the infusion of the drug should be stopped immediately, the remaining dose is injected into another vein.

    During and for at least three months after cessation of therapy, reliable methods of contraception should be used.

    If vinorelbine enters the eye, they should be washed and rinsed thoroughly with water.

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

    Studies of the influence of vinorelbine on the abilities necessary for driving and mechanical equipment were not conducted.

    Form release / dosage:

    Concentrate for the preparation of a solution for infusions of 10 mg / ml (10 mg / ml, 35 mg / 3.5 ml and 50 mg / 5 ml).

    Packaging:

    For 1 ml, 3.5 ml and 5 ml in bottles of colorless and light-protective glass, hermetically sealed with rubber stoppers, with capping aluminum or aluminum-plastic caps. Each vial with instructions for use is placed in a pack of cardboard. 5 or 10 vials together with the instruction for use are placed in a pack with partitions or special cardboard sockets.For 50, 85, 100 bottles with an equal number of instructions for use are placed in a box of cardboard (for hospitals).

    Storage conditions:

    In the dark place at a temperature of 2 to 8 ° C. Keep out of the reach of children!

    After additional dilution, the shelf life is 24 hours (at room temperature).

    Shelf life:

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

    Terms of leave from pharmacies:On prescription
    Registration number:P N003822 / 01
    Date of registration:04.02.2010 / 29.08.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp21.03.2018
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