Bleomycin

When ATH:
L01DC01

Characteristic.

A mixture of glycopeptide antibiotics (A₂, IN₂ and the other fraction), isolated from the strain Streptomyces verticillus (as hydrochloride or sulfate). 1 mg = 1 ME.

Pharmacological action.
Antitumor.

Application.

Squamous cell carcinoma of the skin, head and neck cancer (including the oral mucosa, nadhortannuyu region, larynx, mindaliny, nd- and nasopharynx, sinuses), penile cancer, vulva, cervix, light, Thyroid, esophagus (in combination with radiation therapy); germ cell tumors of the ovary and testis, in t. no. embryonic cell, defense- and teratocarcinoma stage I and II (preferably in combination, in t. no. with vinblastine); malignant lymphoma (Hodgkins, non-Hodgkin's); retikulosarkoma; gliomas; Kaposi's sarcoma in AIDS; pleural effusion, accompanying malignant tumors (treatment and prevention as a sclerosing agent).

Contraindications.

Hypersensitivity, pulmonary insufficiency with severe respiratory failure, fibrosis lyegkikh, severe diseases of the cardiovascular system, renal failure, pregnancy, lactation.

Restrictions apply.

Impaired lung function and / or liver, severe renal impairment, Peripheral Vascular Disease, prior chemotherapy- or radiotherapy, childhood.

Pregnancy and breast-feeding.

Contraindicated in pregnancy. At the time of treatment should stop breastfeeding. Perhaps the demonstration of mutagenic and carcinogenic effects (during pregnancy also teratogenicity), and the development of adverse effects (similar side effects in adults) fetus and newborn.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): rarely is a toxic effect on the blood vessels, including cerebral artery, stroke, myocardial infarction, thrombotic microangiopathy, Raynaud's syndrome, angialgiya, bleeding.

From the respiratory system: manifestations of respiratory toxicity: decrease in the diffusion capacity of the lungs, crepitation, pneumonitis, progressiruющiй to legochnogo fibrosis; coughing and shortness of breath in 10-40% of patients usually after 4-10 weeks after initiation of treatment and before 1 Months after its termination.

From the digestive tract: nausea, vomiting, loss of appetite, diarrhea, rarely is hepatotoxic action (Changes in liver function tests) stomatitis, incl. Angular, due to a toxic effect on the mucous membranes.

With the genitourinary system: rarely — nefrotoksicescoe effects (Changes in kidney function), oligurija, urodynia, thamuria, vulvyt.

For the skin: more often — a toxic effect on the skin (25-50% of patients usually 2-4 weeks after initiation of treatment) and mucous membranes: darkening or thickening of the skin, itch, skin rash, or the appearance of colored cones at their fingertips, elbows or palms, redness or tenderness of the skin, redness fingertips, dark stripes on the skin, swelling of the fingers, change and brittle nails; less often-reversible hair loss (It begins a few weeks after starting treatment).

Allergic reactions: itch, urticaria and other, up to anaphylactic shock, less frequently-idiosinkrazicheskaja reaction (gipotenziya, confusion, fever, chills, wheezing).

Other: weight loss (prolonged use), fever and chills (in 20-60% of patients, usually develop 3-6 h after application, ongoing 4-12 hours and occur less frequently with the continuous introduction of), flebyt and thrombosis (at excess speed / introduction); intraplevralnoe introduction-local pain, pain in tumor lesions; infectious diseases (prolonged use), hyperesthesia distal (nail) falang, conjunctivitis.

Cooperation.

It enhances the effect of general anesthesia pnevmotoksicheskoe (sensitizes lung tissue oxygen). Other antineoplastic agents or radiation therapy increase the toxic effect of the additive and inhibit the function of bone marrow. Cisplatin slows the clearance and enhances the toxic effect (even at low doses). Vincristine enhances the action (arrests the cell cycle in the mitotic phase and increases the sensitivity of cells to bleomycin).

Dosing and Administration.

B /, / m, B / A, n / a, in cavity.

In/in slowly over 5-10 minutes — in a dose of 15-30 mg (in 5-20 ml izotoniceski solution of sodium chloride or 5% glucose solution), which corresponds to 15-30 IU, v/m and m/-15-30 mg (in 1-5 ml of sterile water for injection, isotonic sodium chloride solution or 5% glucose solution), in/and is 5-15 mg (in 5-20 ml optimum solvent). Adults give usually dose 15 mg a day or 30 mg 2 times a week. Heading dose no more than 5-6 mg/kg (to 300-400 mg). Repeated courses with caution, reducing single and course dose, interval between courses 1.5-2 months. Supportive therapy is 15 mg 1 every 7-10 days. People aged patients is 15 mg 2 times a week (the course is not more than 200 mg / m²), children reduce the dose according to body weight. For vnutriplevral'nogo the introduction of 50-60 mg throw in 40 ml izotoniceski solution, introduced after evacuation of the maximum possible number of pleural fluid.

Precautions.

Treatment should be carried out under medical supervision, has experience in anticancer therapy. With caution is prescribed for pulmonary diseases, incl. history, human liver and kidneys, cardiovascular diseases, varicella (a high risk of death), older patients 60 years (increased risk of toxic effects on the lungs, probable age of renal dysfunction), smoking patients (more likely toxic effects on the lungs), children (increased risk of side effects and adverse effect on the function of the gonads), surgical interventions (including dental). Newborns, premature and young children appointment only for health reasons, under constant surveillance. Great caution must use after previous treatment with cytotoxic drugs and radiation therapy, particularly in the chest area, Head and Neck. Care must be taken in combination therapy (Each drug taking in due time). The treatment period is necessary to conduct liver and kidney samples. With the emergence of symptoms of pneumonia, in the event of skin changes (evidence of accumulation) drug overturned; increased body temperature through 4-5 h after injecting requires dose reduction. Women of childbearing age is recommended to use contraceptives.

The toxic effects on the lungs depends on the age of the patient and administration, the most frequently diagnosed in patients over 70 s and / or in patients, receiving a dose above 400 mg (400 ME). In some cases, toxic effects on the lungs was noted at doses of 20-60 mg. Pnevmotoksichnost may be irreversible, sometimes fatal (in some cases, the symptoms disappeared survivors, and lung function returned to normal after about 2 year). Toxic effects developed at lower doses in patients, who received other anticancer drugs or radiation therapy of the chest (irradiated patients mortality may be 10%). When administered low doses can also hypersensitivity pneumonitis. Displaying, that the introduction of bleomycin by continuous on/in infusions for 24 h has a less pronounced toxic effects on the lungs, reduces idiosyncratic reactions, in contrast to the intermittent administration, although the toxic effect on the mucous membranes and skin can be improved.

Cautions.

For early detection of side effects during treatment must: measurement of body temperature every 3 hours after injection, inspection of the skin and visible mucous membranes least 2 once a week, auscultation of the lungs, X-ray of the lungs 1 once every 2 Sun, blood and urine tests at least 1 times a week, pulmonary function tests, incl. lung diffusion capacity for carbon monoxide during a single breath, and forced vital capacity. Treatment should be discontinued at the first sign of lung function (forced vital capacity less 75%). Treatment is symptomatic idiosyncratic reaction (increased fluid intake, the introduction of a vasoconstrictor, antihistamines and corticosteroids). It should be taken into account, that hair growth is restored within a few months after the end of treatment.

Observe safety measures and rules for preparation and dilution of bleomycin (in a sterile box with the use of disposable surgical gloves and masks) and disposal of needles, syringes, bottles, ampoules and unused residues of the drug. Avoid the introduction of the solution when you change the color and the presence of large particles. For injection using freshly prepared solutions.

It should be taken into account, what in vitro inactivated drug substances, containing sulfhydryl groups, hydrogen peroxide and ascorbic acid.