BiKNU® (BiCNU®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCarmustineCarmustine
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  • BiKNU®
    lyophilizate in / in 
    Emkure Pharmaceuticals Co., Ltd.     India
    • Dosage form: & nbsplyophilizate for solution for infusion
    Composition:

    One bottle of the drug contains:

    active substance: carmustine 100 mg;

    Excipients: no.

    One ampoule of the solvent contains: ethanol 3.0 ml.

    Description:

    Lyophilizate: small individual flakes or lyophilized mass of light yellow color.

    Solvent: transparent colorless volatile liquid.

    Pharmacotherapeutic group:An antitumour agent, an alkylating compound
    ATX: & nbsp

    L.01.A.D.01   Carmustine

    Pharmacodynamics:

    BiKNU® (carmustine) is an antitumor drug, a derivative of nitrosourea. It is assumed that carmustine is able to alkylate DNA and RNA, to suppress a number of key enzymatic processes due to carbamoylation of amino acids in proteins.

    Has no cross-resistance to other alkylating drugs.
    Pharmacokinetics:

    After intravenous administration carmustine rapidly metabolized with the formation of active metabolites-isocyanates. 15 minutes after the administration, the unchanged drug is not found in the body.

    At physiological values, pH slightly ionizes, is readily soluble in lipids, penetrates the blood-brain barrier.With the introduction of the radioactive isotope of the preparation, radioactivity was accumulated in the cerebrospinal fluid, where the concentration is 50% or more higher than that in the blood plasma.

    It is assumed that pharmacological action is possessed by metabolites of carmustine, which also respond to the side effects of the drug. 60-70% administered dose is excreted by the kidneys for 96 hours; lungs with exhaled air - 10%, with bile - 1%.

    In case of impaired renal function and in old age, cumulation of the drug is possible (reduction of renal filtration).

    Indications:

    The BiKNU ® preparation is indicated for palliative treatment in the form of monotherapy or in combination with other chemotherapeutic drugs for the following diseases:

    - malignant brain tumors (glioblastoma, glioma of the brainstem, medulloblastoma, astrocytoma, ependymoma) and metastases in the brain of tumors of various locations;

    - multiple myeloma (in combination with prednisolone);

    - lymphogranulomatosis (as part of combination therapy of the second line in patients with relapse after primary therapy or when it is ineffective);

    - non-Hodgkin's lymphomas (as part of combined second-line therapy in patients with relapse after primary therapy or when it is ineffective);

    - malignant melanoma.
    Contraindications:

    - Hypersensitivity to carmustine or other components of the solution for infusion;

    - pregnancy and the period of breastfeeding;

    - Children's age (safety and efficacy not established).

    Carefully:Inhibition of bone marrow function (including on the background of concomitant chemotherapy or radiation therapy, especially when irradiating the mediastinum region), acute infectious diseases of viral, fungal or bacterial nature (including chicken pox, shingles), hepatic insufficiency, respiratory failure, chronic renal failure insufficiency, smoking (because of the increased risk of toxic effects on the lungs).
    Pregnancy and lactation:

    Application during pregnancy and during lactation is contraindicated.

    Dosing and Administration:

    The drug is administered as an intravenous infusion, slowly, for 1-2 hours.

    Do not administer the drug as a rapid intravenous injection.

    Mode of administration:

    - Monotherapy of the first line: 200 mg / m2 once or 100 mg / m2 two days in a row. Repeated administration - no less than 6 weeks.

    - When combined with other myelosuppressive antitumor drugs, and with a decrease in the patient's bone marrow function, the dose is reduced by 30-50%.

    The blood formula is regularly monitored, repeated doses of the drug are administered only when the number of leukocytes is restored to 4000 / μl and platelets to 100,000 / μl, which is usually observed no earlier than 6 weeks after the previous administration of carmustine.

    To adjust the dose for subsequent administrations depending on the number of leukocytes and platelets after the introduction of the previous dose, the following scheme is proposed:

    The minimum level after the previous dose

    Percent from previous dose

    Leukocytes / μL

    Platelets / μL

    >4000

    >100 000;

    100%

    3 000-3 999

    75 000-99 999

    100%

    2 000-2 999

    25 000- 74 999

    70%

    <2000

    <25 000

    50%
    Preparation of the solution

    To facilitate dissolution prior to mixing, the drug vial and ampoule of the solvent are removed from the refrigerator and left at room temperature (15-30 ° C) in a dark place for several minutes. A solution for intravenous administration is prepared by adding 3 ml of the supplied solvent - sterile anhydrous ethanol for injection into the vial. After completely dissolving in ethanol, 27 ml of sterile water for injection is added under aseptic conditions to the resulting ethanol solution.A clear, slightly yellowish solution forms, 1 ml of which contains 3.3 mg of carmustine in 10% ethanol, the pH of the solution is 5.6-6.0. The prepared solution is stable for 24 hours when stored in a refrigerator (2-8FROM). Before use, the solution should be inspected for crystals. The crystals disappear at room temperature and agitation.

    The resulting solution is further diluted with 0.9% sodium chloride or 5% dextrose solution to a concentration of no more than 0.5 mg / ml. The diluted solution should be used within 8 hours while it needs to be protected from light. This solution can also be stored in the refrigerator (2-8° C) for 24 hours and then for another 6 hours at room temperature, protecting from light.

    The drug does not contain preservatives, so it is not intended for repeated use. Unused solution of the drug in the vial is destroyed.

    ATTENTION: carmustine has a low melting point (about 30.5-32.0 ° C); storage at this temperature or higher leads to melting of the preparation and formation of an oily film on the bottom of the vial. The presence of oily film indicates the destruction of the active substance, so this drug should be destroyed.

    Before use, the contents of the vial removed from the refrigerator are examined under bright light: the drug suitable for use is in the form of dry flakes or dry cake. If the drug is not intended for immediate use, it should be stored in the refrigerator.

    To minimize the effects of the drug on the skin, always wear gloves when handling the vials containing the drug.

    Side effects:

    Infections: opportunistic infections, sometimes fatal.

    Co hematopoiesis side: leukopenia, thrombocytopenia, neutropenia, bleeding, acute leukemia, bone marrow dysplasia, anemia.

    From the respiratory system: pulmonary infiltration, pulmonary fibrosis (fatal)

    From the side of the digestive system: nausea, vomiting, decreased appetite.

    From the nervous system: asthenia, dizziness, headache.

    From the urinary system: decrease in kidney size, kidney failure.

    From the cardiovascular system: lowering of blood pressure, tachycardia.

    From the side of the organ of vision: impaired vision, neuroretinitis.

    Allergic reactions: a rash, itching, swelling and redness of the conjunctiva, a rush of blood to the skin of the face.

    Reactions at the site of administration: burning sensation, soreness and swelling at the injection site, phlebitis, erythema, necrosis of the skin.

    Other: pain in the chest.

    Change in laboratory indicators: increased activity of serum transaminase, alkaline phosphatase, increased serum bilirubin concentration, azotemia.

    Overdose:

    Symptoms: increased effect of side effects.

    Treatment: a specific antidote is not known. Treatment is symptomatic.
    Interaction:

    In connection with the increased risk of thrombosis in oncological patients, they are often prescribed anticoagulant therapy. In the case of a course of treatment with a cytostatic drug against the background of taking oral anticoagulants, it is necessary to conduct regular studies of the factor of coagulability of blood in connection with the possible interaction of an anticoagulant and a cytostatic drug.

    In connection with the possible decrease in the absorption of phenytoin and phosphenytoin in the gastrointestinal tract under the influence of the cytostatic drug, the development of seizures is possible; Besides,as a result of the possible enhancement of hepatic metabolism of the cytotoxic drug under the influence of phenytoin and phosphenytoin, toxicity or loss of efficacy of the cytotoxic drug is possible.

    Carmustine reduces the production of antibodies in response to the administration of a weakened live viral vaccine; It is also possible to strengthen the replication process of the vaccine virus and to increase the side effects caused by it. The interval between cessation of treatment with carmustine and vaccination should be from 3 months to 1 year.

    When vaccinating against yellow fever during treatment with the drug, there is a risk of developing fatal generalized vaccine disease.

    With the joint use of carmustine and cimetidine, leukopenia and neutropenia are more severe than with the use of only carmustine. It is not recommended to appoint simultaneously with other drugs that have myelosupressive, nephrotoxic or hepatotoxic effects.

    Special instructions:

    Treatment with BiKNU® should be performed under the supervision of a physician with experience in chemotherapy.

    During treatment with the drug should periodically conduct a functional study of the liver and kidneys. Disturbance of liver function is reversible.

    Violation of kidney function and renal failure are observed, as a rule, when using large total doses of the drug for a long time.

    Pulmonary toxicity, characterized by the appearance of lung infiltrates and / or the development of fibrosis, is observed in almost 30% of patients, usually within the first 3 years after treatment with the drug. Pulmonary toxicity of carmustine depends on the dose. In patients receiving the drug at doses of 1200-1500 mg / μL (cumulative dose), the risk is higher than in patients receiving lower doses. Before starting treatment conduct a functional examination of the lungs, which is periodically repeated in the process therapy. The risk group consists of patients with initial indices of forced vital capacity of lungs (FVC) and lung capacity for diffusion of CO less than 70% of the norm.

    The risk of pulmonary toxicity (including fatal outcome) increases with respiratory diseases, smoking, as well as with prolonged therapy and radiation therapy.The cases of late development of pulmonary fibrosis within 17 years after treatment with the drug in childhood or in early adolescence in cumulative doses from 770 to 1800 mg / m2 in combination with radiation therapy of brain tumors. This form of lung fibrosis can be of a slowly progressive nature and can lead to death.

    The main manifestation of the toxicity of carmustine is myelosuppression, therefore the blood picture should be determined weekly, at least for 6 weeks after the administration of the drug. Oppression of the bone marrow is dose-dependent. Leukopenia is usually observed 5-6 weeks after drug administration and lasts 1-2 weeks. Thrombocytopenia develops approximately 4 weeks after the administration of the drug and persists for 1-2 weeks; it is usually of a more severe character than leukopenia. With leukopenia and thrombocytopenia, a dose reduction may be required. The drug may cause cumulative myelosuppression, which is manifested by lower concentrations of blood cells or longer duration of myelosuppression after the administration of repeated doses of the drug.

    Nausea and vomiting develop usually 2 hours after the administration of the drug and last 4-6 hours. Their severity depends on the dose; Premedication with antiemetic drugs can prevent nausea and vomiting or significantly reduce their manifestation.

    Most adverse reactions are reversible with the timely taking of the necessary measures. If side effects are detected, the dose of the drug should be lowered or the treatment stopped, if necessary, appropriate corrective measures are taken. Resumption of treatment with carmustine should be conducted carefully, after assessing the need for further use of the drug due to the possible recurrence of side effects.

    There are reports of the development of secondary malignant tumors due to prolonged use of nitrosoureas.

    You should not prescribe the drug in combination with vaccination against yellow fever due to the risk of developing a fatal generalized vaccine disease.

    When appointing the drug BKNU® patients with impaired liver function, suffering from epilepsy or alcohol abuse, it should be taken into account that the solution for infusions contains 10% ethanol.

    During intravenous infusion of the drug, reactions at the site of administration are possible. Given the possibility of bruising and bruising, it is necessary to regularly check the place of administration of the drug for the presence of infiltration.

    When working with BiKNU®, the rules for handling and destroying antitumor drugs should be observed. It is recommended to use gloves.

    The accidental contact of the drug or its solution with the skin causes a burning sensation and hyperpigmentation of the affected areas.

    If the product or its solutions get into the skin or mucous membranes, they should be washed immediately and thoroughly with soap and water.

    Form release / dosage:Lyophilizate for the preparation of a solution for infusions of 100 mg.
    Packaging:

    100 mg lyophilizate in a bottle of dark glass, ukuporenny brombutilovoy stopper and aluminum cap "under the break-in" with a protective plastic lid.

    3 ml of solvent in ampoule of colorless glass type I.

    1 bottle with lyophilizate, 1 ampoule with a solvent and instructions for medical use are placed in a cardboard pack.

    Storage conditions:

    Store at 2-8 ° C (in the refrigerator).

    Keep out of the reach of children.

    Shelf life:

    3 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:П N015891 / 01
    Date of registration:16.07.2009
    The owner of the registration certificate:Emkure Pharmaceuticals Co., Ltd.Emkure Pharmaceuticals Co., Ltd. India
    Manufacturer: & nbsp
    Representation: & nbspEMKYUR PHARMACEUTICALS LIMITEDEMKYUR PHARMACEUTICALS LIMITEDRussia
    Information update date: & nbsp23.03.2015
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