Vinorelbine-Teva (Vinorelbine -Teva)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceVinorelbineVinorelbine
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    • Dosage form: & nbspconcentrate for solution for infusion
    Composition:

    In 1 ml of the concentrate contains:

    active substance: vinorelbine (vinorelbine ditartrate) 10.0 (13.85) mg; Excipients: water for injections.
    Description:Transparent solution from almost colorless to light yellow color.
    Pharmacotherapeutic group:Antitumor agent, alkaloid
    ATX: & nbsp

    L.01.C.A.04   Vinorelbine

    Pharmacodynamics:

    Vinorelbine is an antitumor agent of plant origin from the group of semisynthetic vinca alkaloids isolated from a plant of the genus Vinca (vinca alkaloid pink, obtained semi-synthetically). Violates the polymerization of tubulin in the process of cellular mitosis. It blocks the mitosis of cells at the stage of metaphase G2-M, causing cell death during interphase or subsequent mitosis. Acts mainly on mitotic microtubules; When high doses are applied, the axonal microtubules also have an effect. The effect of spiral tubulin, caused by vinorelbine, is less pronounced than that of vincristine.

    Pharmacokinetics:
    Distribution
    The volume of vinorelbine distribution is high, averaging 21.2 l / kg (range 7.5-39.7 l / kg), which indicates an extensive distribution of vinorelbine in tissues.
    Binding to plasma proteins is insignificant - 13.5%, vinorelbine in large quantities binds to blood cells, especially with platelets (about 78%). There is a significant seizure of vinorelbine with a pulmonary tissue, where a concentration of 300 times higher than in the blood plasma is achieved. Vinorelbine is not found in the brain tissues.
    Metabolism
    Vinorelbine is biotransformed in the liver under the action of the cytochrome P450 isoenzyme CYP3A4. All metabolites are identified and inactive, with the exception of 4-O-deacetyl-vinorelbine, which is the main active metabolite in the blood plasma. Sulfo- and glucuronic conjugates were not detected.
    Excretion
    The average half-life of vinorelbine in the final phase of elimination is about 40 (27.7-43.6) hours. Systemic clearance of vinorelbine is high and approaches the rate of blood flow in the liver, is on average
    0.72 l / h / kg (0.32-1.26 l / h / kg). Vinorelbine mainly excreted in the bile in unchanged form and in the form of metabolites. The kidneys produce less than 20% of the intravenously administered dose, mainly as a starting material. Pharmacokinetics in specific patient groups
    Patients with impaired hepatic function
    The pharmacokinetics of vinorelbine does not change in patients with hepatic insufficiency. Nevertheless, as a precautionary measure, it is recommended to reduce the dose to 20 mg / m2 of the body surface and carefully monitor hematological parameters in patients with moderate or severe hepatic impairment.
    Patients with impaired renal function
    The effect of renal dysfunction on the pharmacokinetic properties of vinorelbine has not been investigated. However, due to the low level of renal elimination, a decrease in vinorelbine dose in the case of decreased renal function is not indicated.
    Elderly patients
    The pharmacokinetics of vinorelbin in elderly patients (≥ 70 years) does not change. However, since elderly patients may be weakened, precautions should be taken when increasing the dose of vinorelbine.
    Indications:- non-small cell lung cancer;
    - common breast cancer;
    - hormone-resistant prostate cancer (in combination with treatment with oral glucocorticosteroids in small doses).
    Contraindications:
    - Hypersensitivity to vinca alkaloids or other components of the drug.
    - The initial content of neutrophils is less than 1500 cells / μl of blood and platelets less than 100,000 cells / μl of blood.
    - Severe infectious diseases during the initiation of therapy or transferred during the last 2 weeks.
    - Pregnancy and the period of breastfeeding.
    - Child age (lack of safety and efficacy data).
    - Simultaneous use with the vaccine against yellow fever.
    Carefully:
    With ischemic heart disease, hepatic insufficiency of moderate and severe degree, respiratory failure, oppression of bone marrow hematopoiesis (including after previous chemotherapy or radiation treatment), constipation or intestinal obstruction in history, neuropathy in history, simultaneous intake of inhibitors or inducers of isoenzyme CYP3A4.
    Pregnancy and lactation:
    The drug Vinorelbin-Teva is contraindicated during pregnancy in connection with embryotoxic action.
    The drug Vinorelbin-Teva is contraindicated in the period of breastfeeding. Breastfeeding should be discontinued before taking the drug.
    Dosing and Administration:
    The drug Vinorelbin-Teva is administered strictly intravenously. Strongly forbidden intrathecal injection of the drug Vinorelbin-Teva, this method of administration leads to a lethal outcome!
    Dosage regimen, frequency of administration and duration of treatment are determined by the attending physician.
    The drug is administered as a 6-10 minute infusion.Preliminary concentrate is diluted in 20-50 ml of 0.9% solution of sodium chloride for injection or in a 5% solution of dextrose for injection. Immediately after the administration of the drug should be introduced at least 250 ml of 0.9% sodium chloride solution to flush the veins.
    Non-small cell lung cancer and advanced breast cancer
    In the monotherapy regimen, the standard dose of the drug is 25-30 mg / m2 body surface once a week.
    With combined chemotherapy, the standard dose of the drug is 25-30 mg / m2 body surface, but the frequency of administration decreases - on days 1 and 5 every 3 weeks or on days 1 and 8 every 3 weeks - depending on the protocol of antitumor therapy.
    Prostate Cancer Resistant to Hormone Therapy
    The usual dose of the drug is 30 mg / m2 body surface on days 1 and 8 every 3 weeks in conjunction with daily intake of oral glucocorticosteroids in low doses (for example, hydrocortisone in a dose of 40 mg / day).
    Correction of dosing regimes
    Hematological toxicity
    With a decrease in the absolute number of neutrophils of less than 1500 cells / μl and / or platelets of less than 100,000 cells / μl of blood, Vinorelbine - Teva is postponed until the number of neutrophils is restored ≥ 1500 cells / μl and / or platelets ≥ 100,000 cells / μl.
    With hepatic insufficiency of moderate and severe severity The dose of Vinorelbin-Teva should be reduced to 20 mg / m2, patients should be monitored for hematologic parameters.
    Children: safety and efficacy of Vinorelbin-Teva in children have not been studied.
    Older patients: correction of the dose is not required.
    Side effects:
    The incidence of side effects is classified according to the recommendations of the World Health Organization: very often (≥ 1/10); often (≥ 1/100, but <1/10); infrequently (≥ 1/1000, but <1/100); rarely (≥ 1/10000, but <1/1000); very rarely (<1/10000), including individual messages; the frequency is unknown - the frequency can not be estimated from the available data.
    Infectious and parasitic diseases: often - bacterial, viral or fungal infections of the respiratory, urinary and gastrointestinal tract from mild to moderate severity, usually reversible with appropriate treatment; infrequently - severe sepsis with multiple organ failure, septicemia; very rarely - complicated septicemia, sometimes fatal; frequency unknown - neutropenic sepsis.
    From the side of the blood and lymphatic system: very often - myelosuppression leading to neutropenia (the smallest number of neutrophils is observed on the 7-10th day from the initiation of therapy, recovery occurs in the next 5-7 days, cumulation of hematotoxicity is not observed), anemia; often - thrombocytopenia; frequency unknown - febrile neutropenia.
    From the immune system: often - allergic reactions (skin reactions, respiratory reactions); frequency unknown - systemic allergic reactions (anaphylaxis, anaphylactic shock or anaphylactoid type reactions, angioedema).
    From the endocrine system: frequency is unknown - syndrome of inadequate secretion of anhydrous hormone.
    From the side of metabolism and nutrition: rarely severe hypnasatremia; frequency is unknown - anorexia.
    From the nervous system: very often - neurological disorders, including a decrease or loss of tendon reflexes; infrequently - severe paresthesias with sensory and motor symptoms, usually reversible; frequency is unknown - weakness of the lower extremities with prolonged chemotherapy.
    From the heart: rarely - ischemic heart disease (angina), myocardial infarction, transient changes in the electrocardiogram; very rarely - tachycardia, fibrillation, heart rhythm disturbances, palpitation.
    From the side of the vessels: infrequently - arterial hypotension, arterial hypertension, sensation of "hot flashes", cooling of limbs; rarely - severe arterial hypotension, collapse.
    From the respiratory system, chest and mediastinum: infrequently - shortness of breath, bronchospasm; rarely - interstitial pneumonia.
    From the gastrointestinal tract: very often - stomatitis, nausea, vomiting, constipation; often diarrhea (usually of mild or moderate severity); rarely - paralytic intestinal obstruction, pancreatitis.
    From the liver and bile ducts: very often - a transient increase in the activity of "liver" transaminases without clinical symptoms.
    From the skin and subcutaneous tissues: very often - alopecia (usually a moderate degree); rarely - generalized skin reactions; frequency is unknown - erythema on the palms and feet.
    From the osteomuscular system and connective tissue: often - arthralgia, pain in the temporomandibular joint, myalgia.
    From the side of the kidneys and urinary tract: often - increasing the concentration of creatinine in the blood serum.
    General disorders and disorders at the site of administration: very often - asthenia, weakness, fever, pain of different locations, including pain in the chest and in the tumor region, reactions at the site of administration may include erythema, burning pain, vein discoloration and phlebitis at the site of administration; rarely - tissue necrosis at the injection site.
    Overdose:
    The main toxic effect due to overdose is the suppression of bone marrow function, sometimes in combination with infection, fever, dynamic intestinal obstruction and impaired liver function. The specific antidote is unknown.
    In case of an overdose, it is necessary to hospitalize the patient and carefully monitor the functions of vital organs. Appropriate measures should be taken: blood transfusion, administration of antibiotics, growth factors.
    Monitoring of liver function is recommended.
    Interaction:
    Pharmaceutical interaction
    Do not use alkaline solutions to dilute the concentrate (possibly precipitation).
    Do not mix the ready-made solution for vinorelbine infusions with other medications for intravenous administration.
    Pharmacodynamic interaction
    Vaccines: in connection with the immunosuppressive effect of vinorelbine and the possibility of developing severe infections, it is not recommended during the period of chemotherapy to carry out vaccination with live (weakened) vaccines.
    When combined with paclitaxel, the risk of neurotoxicity increases. Application on the background of radiation therapy leads to radiosensitization. The use of vinorelbine after radiation therapy can lead to the re-emergence of radiation reactions.
    The simultaneous use of vinorelbine with a vaccine against yellow fever is contraindicated.
    Itraconazole: an increase in the neurotoxicity of vinorelbine due to an increase in the concentration of vinorelbine in the plasma as a result of a decrease in its metabolism in the liver.
    Phenytoin: it is possible to reduce the anticonvulsant effect of phenytoin, decrease the efficacy and increase the toxicity of vinorelbine.
    Cisplatinum: There is no mutual influence in the combined use of vinorelbine and cisplatin for several treatment cycles.However, the frequency of cases of granulocytopenia with the use of a combination of vinorelbine with cisplatin is higher than in the case of monotherapy with vinorelbine.
    Cytotoxic: possibly mutual aggravation of side effects, in the first place - myelosuppression.
    Oral anticoagulants: the mutual aggravation of side effects is possible, the INR (international normalized relationship) should be systematically monitored, as well as careful monitoring of the patient's general condition.
    Cyclosporin, tacrolimus: marked immunosuppression with risk of lymphoproliferation.
    Inhibitors of the isoenzyme CYP3A4 (eg, ketoconazole): an increase in the neurotoxicity of vinorelbine due to an increase in vinorelbine concentration in the blood plasma as a result of a decrease in its metabolism in the liver.
    Inductors of the isoenzyme CYP3A4 (for example, rifampicin): decreased efficacy and increased toxicity of vinorelbine due to increased metabolism in the liver.
    Inductors and inhibitors of cytochrome P450: a change in the pharmacokinetics of vinorelbine is possible.
    Mitomycin C: increased pulmonological toxicity mitomycin (risk of bronchospasm, acute respiratory failure, there were rare cases of interstitial pneumonia).
    Inductors and inhibitors of P-glycoprotein: since it is known that vinca alkaloids are a substrate for P-glycoprotein, caution should be exercised when using vinorelbine jointly with preparations that alter the function of this transport protein.
    Special instructions:
    The drug Vinorelbin-Teva is intended exclusively for intravenous administration. Strongly forbidden intrathecal injection of the drug Vinorelbin-Teva, this method of administration leads to a lethal outcome!
    Treatment should be conducted under the supervision of a doctor who has experience with antitumor drugs. During the treatment should be a thorough hematological monitoring - the number of leukocytes, neutrophils, platelets and hemoglobin on the day of each injection.
    In case of suspected co-infection on the day of initiation of therapy, the patient should be examined and the benefit-risk ratio should be evaluated when deciding whether to administer the drug.
    If dyspnoea, cough or hypoxia of unexplained etiology appears, the patient should be examined to exclude pulmonary toxicity.
    In the case of development of dynamic intestinal obstruction, the drug should be discontinued.Treatment can be continued after restoration of normal intestinal motility.
    The contact of the concentrate with skin, mucous membranes or in the eyes can lead to burns. If this happens, the affected areas should be washed immediately and thoroughly with 0.9% sodium chloride solution.
    Vinorelbine-Teva should not be used concomitantly with X-ray therapy, which is especially exciting for the liver region.
    The drug Vinorelbin-Teva should be used with caution with inhibitors or inducers of the isoenzyme CYP3A4; simultaneous use of the drug with phenytoin, itraconazole, live attenuated vaccines is not recommended.
    In case of hepatic insufficiency of moderate and severe degree, the dose of Vinorelbin-Teva should be reduced, in patients it is necessary to control haematological parameters.
    If the kidney function is impaired, intensive monitoring of the patient is necessary. Care should be taken when using Vinorelbin-Teva in patients with coronary heart disease.
    Impact on fertility
    Men and women should use reliable methods of contraception during the treatment with vinorelbine, and also within three months after the end of chemotherapy.Patients who plan to have children after treatment are recommended for genetic counseling.
    Due to the possibility of developing an irreversible loss of fertility as a result of treatment with vinorelbine, patients should be given a recommendation for preserving sperm before starting treatment with vinorelbine.
    When there are signs of neurotoxicity of the 2nd and more degree, the drug Vinorelbin-Teva should be discontinued.
    When extravasation, the infusion of the drug should be stopped immediately, the remaining dose is injected into another vein.
    Instructions for the introduction of ready-made mortar and waste management
    Preparation of a solution for intravenous administration of the drug Vinorelbin-Teva should be carried out by medical personnel trained in the work with chemotherapeutic drugs. Personnel should wear eye protection, disposable gloves, a mask and apron. The drug should be administered strictly intravenously: it is very important to make sure that the needle or catheter is accurately set in the vein, before the drug starts.
    When extravasation should stop the infusion, wash the vein with 0.9% solution of sodium chloride, the remainder of the dose to enter another vein.In the case of extravasation, to reduce the risk of phlebitis, glucocorticosteroids should be injected intravenously. Unused solution or waste must be disposed of in accordance with the regulations of the treatment and prophylactic establishment.
    Effect on the ability to drive transp. cf. and fur:Special studies on the effect of the drug on the ability to drive vehicles and control mechanisms have not been conducted. However, patients are not advised to drive vehicles and engage in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions if they experience adverse reactions that may affect the performance of this activity.
    Form release / dosage:Concentrate for the preparation of a solution for infusion of 10 mg / ml,
    Packaging:At 10 mg / 1 ml and 50 mg / 5 ml in bottles of colorless glass with plugs of chlorobutyl rubber and aluminum caps, is equipped with a protective cap made of colored polypropylene. 1 bottle, placed in a transparent pallet LSB, together with instructions for use in a cardboard bundle.
    Storage conditions:List B.
    In the dark place at a temperature of 2 to 8about FROM.Do not freeze.
    Keep out of the reach of children.
    Shelf life:2 years.
    Do not use after the expiration date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-009543/09
    Date of registration:25.11.2009
    Expiration Date:Unlimited
    The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel
    Manufacturer: & nbsp
    Representation: & nbspTeva Teva Israel
    Information update date: & nbsp16.02.2017
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