Bleomycetin hydrochloride (Bleomycetin hydrochloride)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceBleomycinBleomycin
Similar drugsTo uncover
  • Blenamax
    lyophilizate for injections 
    Teva Pharmaceutical Enterprises Co., Ltd.     Israel
  • Bleomycetin hydrochloride
    lyophilizate for injections 
    SPbNIIVS FMBA, FSUE     Russia
  • Bleomycin-RONTS®
    lyophilizate for injections 
    RNTS named after N.N. Blokhin RAMS     Russia
  • Bleocin
    lyophilizate for injections 
    Nippon Kayaku Co., Ltd.     Japan
  • Vero-Bleomycin
    lyophilizate for injections 
    LENS-PHARM, LLC     Russia
    • Dosage form: & nbsplyophilizate for solution for injection
    Composition:

    One ampoule contains:

    active substance: bleomycetin hydrochloride in terms of bleomycetin 5 mg;

    Excipients: Mannitol (mannitol) 20 mg.

    Description:Porous mass of white or yellowish white color. Hygroscopic.
    Pharmacotherapeutic group:Antitumor agent - antibiotic
    ATX: & nbsp

    L.01.D.C.01   Bleomycin

    Pharmacodynamics:

    Bleomycetin hydrochloride (bleomycin fraction As) obtained from the culture Streptomyces verticillus, an antitumor antibiotic, is a a mixture of structurally coupled water-soluble salts of glycopeptide antibiotics, the main component of which is pure bleomycin A5.

    The mechanism of action of bleomycin is based on the fragmentation of DNA molecules in the G1 phase and at the beginning of the S phase of the cell cycle, the destruction of its spiral structure, which leads to inhibition of cell division. Less bleomycin affects RNA and protein synthesis. Has a selective effect against tumors of epidermal origin.

    With intrapleural administration, it exhibits sclerosing properties.

    Unlike most other cytotoxic drugs, bleomycin is low in toxicity to the bone marrow, does not have a significant immunosuppressive effect, is not a neurotoxic and cardiotoxic drug.

    Pharmacokinetics:

    After parenteral administration, it accumulates in the tumor cells of the skin and lungs, to a lesser extent - the kidneys, peritoneum, lymph nodes, and little - in the hemopoietic tissue.

    The mechanism of metabolism is unknown, probably it is carried out by cleavage in tissues with the participation of the bleomycin-hydrolase enzyme. The intensity of metabolism in tissues is variable, which can determine the toxic effect and antitumor effect of bleomycin. Enzyme activity is high in the liver, kidneys in the bone marrow and lymph nodes, but low in the skin and lungs.

    The dynamics of blood concentration is described by the bi-exponential curve; half-life (T1/2) alpha - 25 min, T1/2 Beta - 4 hours.

    With intrapleural or intraperitoneal injection, systemic absorption is 45%.The connection with plasma proteins is negligible.

    In case of creatinine clearance more than 35 ml / min T1/2 is 115 min, less than 35 ml / min - T1/2 increases exponentially as the creatinine clearance decreases.

    It is excreted by the kidneys, 60-70% unchanged (in patients with normal renal function); with moderate chronic renal failure - 20%. When dialysis is probably not output. Total clearance - 50 ml / min / m2.

    Indications:

    Bleomycin is usually used either as monotherapy or in combination with other cytostatics and / or radiation therapy to treat squamous cell forms of skin, head and neck cancer, esophagus, thyroid cancer, cervix, vulva, penis, germinogenic testicular and ovarian tumors, Hodgkin's disease, non-Hodgkin's lymphomas (including lymphosarcoma and reticulosarcoma), Kaposi's sarcoma in AIDS, melanoma, malignant pleurisy (as sclerosing agent), ascites against a background of malignant tumors.

    Contraindications:

    Hypersensitivity to the components of the drug, severe renal failure, respiratory failure (pulmonary fibrosis, chronic interstitial pneumonia), decompensated heart failure, pregnancy, lactation.

    Carefully:

    Inhibition of bone marrow hematopoiesis, renal and / or hepatic insufficiency, previous or concomitant radiotherapy to the thoracic region, varicocele, elderly age, childhood, acute infectious diseases of viral, fungal or bacterial nature (including chicken pox, shingles) .

    Dosing and Administration:

    Intravenous, intramuscular, intracavitary.

    In each individual case, when choosing the dose and mode of administration of Bleomycetin hydrochloride, one should use the literature data.

    Usually bleomycetin hydrochloride is administered:

    - intramuscularly (in 3-5 ml of a 0.9% solution of sodium chloride or water for injection, alternating injection sites) or intravenously slowly (in 15-20 ml of a 0.9% solution of sodium chloride or water for injection for 5-10 minutes ) in a dose of 8-10 mg (4-5 mg / m2) three times a week or 15-20 mg (8-10 mg / m2) two times a week;

    - in the form of intravenous infusion (in 200-1000 ml of 0.9% solution of sodium chloride) for 6-24 hours in a dose of 10-15 mg / m2 daily for 4-7 days with a repetition of the course every 3-4 weeks;

    - intrapleural or in the abdominal cavity of Bloomycetin hydrochloride is administered 50-60 mg in 40 ml of 0.9% sodium chloride solution after evacuation of the maximum possible amount of exudate.

    Because of the risk of developing an anaphylactic reaction, the initial dose, especially for patients with lymphoma, can be reduced (for example, to 2-3 mg / m2). If the acute reaction does not develop, then the drug can be applied in the usual dose.

    The total total dose of Bleomycetin hydrochloride should not exceed 250-300 mg. Further administration of the drug can be carried out with great care and only after determining the lung function.

    In elderly patients, the dose of the drug is determined as follows:

    Age (years)

    Total dose

    Weekly dose

    80 and over

    65 mg

    10 mg

    70-79

    100-140 mg

    20 mg

    60-69

    140-200 mg

    30-40 mg

    less than 60

    250-300 mg

    30-40mg

    Introduction of bleomycetin hydrochloride to children is carried out only in special cases, the determination of the dose of the drug should be carried out from the calculation of the surface of the body.

    When carrying out radiation therapy, the dose of Bleomycetin hydrochloride should be Reduced, because irradiated tissues are more sensitive to the drug.

    Adjustment of the dose of the drug should be carried out and in the event that Bleomycetin hydrochloride is used in combination with other chemotherapeutic drugs.

    In patients with impaired renal function The dose of Bleomycetin hydrochloride is changed as follows:

    - at a serum creatinine concentration of 130-180 μmol / l, the dose of the drug should be reduced by 50%;

    - at a serum creatinine concentration of more than 180 μmol / L, the drug is postponed until the normal values ​​of the creatinine concentration are reached.

    Side effects:

    From the respiratory system: interstitial pneumonia, pulmonary fibrosis, pleurisy with pain syndrome, cough, dyspnea.

    From the nervous system: headache, dizziness.

    Co side of the digestive system: decreased appetite, nausea, vomiting, diarrhea, weight loss (with prolonged use), impaired liver function.

    From the urinary system: impaired renal function.

    From the skin and skin appendages: hyperkeratosis, peeling, hyperemia, hyperpigmentation and itching of the skin, striae, deformation and fragility of nails, hyperesthesia of the skin and distal (nail) phalanges, hyperemia of fingertips, sclerodermal-like skin changes, stomatitis, alopecia.

    Allergic reactions: urticaria, anaphylactoid reactions, idiosyncrasy (lowering blood pressure, confusion, fainting, rising body temperature, chills, stridorous breathing).

    On the part of the reproductive system: azoospermia, amenorrhea.

    Local reactions: phlebitis and thrombosis (when the speed of intravenous injection is exceeded); intrapleural injection - local pain.

    Other: hyperthermia (2 hours after administration with a maximum after 4-8 hours); bleeding due to rapid disintegration of the tumor; cardiovascular disorders (including cerebral, arteritis, stroke, myocardial infarction, thrombotic microangiopathy, Raynaud's syndrome); pain in the area of ​​tumor lesions; a feeling of general malaise; rarely - leukopenia, conjunctivitis, vulvitis, etc. manifestations of the skin and mucous membranes (usually 2-5 weeks after the start of therapy after reaching total doses of 150-200 mg).

    Overdose:

    Immediate acute reactions in case of an overdose are lowering of arterial pressure, fever, rapid pulse, bronchopulmonary complications and general symptoms of anaphylactic shock.

    Treatment symptomatic. With complications from the bronchopulmonary system, patients should be treated with glucocorticosteroids and broad-spectrum antibiotics.

    Interaction:

    With simultaneous administration of bleomycin with carmustine, mitomycin, cyclophosphamide and methotrexate, as well as with the use of oxygen (especially in surgical interventions) and other drugs that have a toxic effect on the lungs (smoking), increases the risk of pulmonary toxicity.

    When combined application bleomycin and vincoalkaloids increases the risk of vascular disorders, In patients with malignant testicular tumor, which is carried out combination treatment bleomycin and preparations from the class of vincoalkaloids, described Raynaud's syndrome.

    Myelotoxic drugs and radiation therapy increase the incidence of side effects.

    With simultaneous use with clozapine, the risk of developing agranulocytosis increases.

    Special instructions:

    Treatment should be carried out under the supervision of a doctor who has experience of antitumor therapy.

    For early detection of side effects during the treatment period, it is necessary to carry out measurement of body temperature every 3 hours after drug administration, examination of the skin and visible mucous membranes at least 2 times in Week, auscultation of lungs, lung radiography once a month, blood and urine analysis at least once a week.

    Newborns, premature babies and young children can be appointed only for life indications, under constant supervision.

    The sensitivity to bleomycetin hydrochloride is increased in elderly patients.

    Great care requires the use of the drug after radiotherapy (especially in the chest, head and neck).

    With ulcerative stomatitis and allergic rash treatment is stopped; when suspected of pneumonia, treatment is immediately stopped and glucocorticosteroids are used against antibiotic therapy.

    When surgical interventions are used with caution, oxygen; at operating oxygen content in the air is not more than 25%.

    Women of reproductive age and men during treatment with Bloomycetin hydrochloride and within three months after the use of reliable methods of contraception.

    Avoid the introduction of a solution when the color changes and large particles are present.

    For the introduction use freshly prepared solutions.

    Care should be taken when preparing the solution and when it is injected; If the product gets on the skin or mucous membranes, they should be washed with plenty of water.
    Effect on the ability to drive transp. cf. and fur:

    The drug may affect the ability to drive vehicles and engage in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions, since the drug can cause nausea, confusion, dizziness, fainting and other side effects that can affect these abilities.

    Form release / dosage:Lyophilizate for solution for injection, 5 mg.
    Packaging:

    5 mg of active substance in the ampoule.

    For 10 ampoules together with a scarifier ampoule or a knife for opening ampoules and instructions for use in a cardboard bundle.

    Storage conditions:

    In a dry, the dark place at a temperature of no higher than 10 ° C.

    Keep out of the reach of children.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-001113
    Date of registration:03.11.2011
    Expiration Date:Unlimited
    The owner of the registration certificate:SPbNIIVS FMBA, FSUE SPbNIIVS FMBA, FSUE Russia
    Manufacturer: & nbsp
    Representation: & nbspSPbNIIVS FMBA, FSUESPbNIIVS FMBA, FSUERussia
    Information update date: & nbsp18.02.2017
    Illustrated instructions
      Instructions
      Up