Bleomycin-RONC - instructions for use, dose, side effects, contraindications

Active substanceBleomycinBleomycin

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lyophilizate for injections

RNTS named after N.N. Blokhin RAMS Russia

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Dosage form: & nbsplyophilizate for solution for injection

Composition:

1 bottle contains:

active substance: bleomycin 15 ED (as bleomycin sulfate);

Excipients: no.

Description:

Porous mass or powder from white to white with a yellowish tint of color.

Pharmacotherapeutic group:antitumor agent - antibiotic

ATX: & nbsp

L.01.D.C.01 Bleomycin

Pharmacodynamics:

Bleomycin refers to antitumor antibiotics and is a mixture of structurally related water-soluble salts of glycopeptide antibiotics derived from a culture Streptomyces verticillus.

The mechanism of action of bleomycin is based on the fragmentation of DNA molecules in G1 phase and at the beginning 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 slightly toxic in respect of bone marrow, does not have a significant immunosuppressive effect and is not a neurotoxic and cardiotoxic drug.

Pharmacokinetics:

After intramuscular injection of the drug at a dose of 15 U / m² the maximum concentration in the plasma is reached 30 minutes after the administration of the drug.

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. With intrapleural or intraperitoneal administration, systemic absorption is 45%. Link with blood plasma proteins is insignificant.

The mechanism of metabolism is unknown; probably, it occurs during the cleavage by enzymes 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.The enzyme activity is high in the liver, kidneys, in the bone marrow and lymph nodes, but less in the skin and lungs. The dynamics of blood concentration is described by the bi-exponential curve; half-life T_1/2 alpha - 25 min, T_1/2 Beta - 4 hours.

In case of creatinine clearance more than 35 ml / min T_1/2 is 115 min, less than 35 ml / min - 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 (creatinine clearance <35 ml / min) - 20% of the drug. 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, germ cell tumors of the testis and ovary , Hodgkin's disease, non-Hodgkin's lymphomas (including lymphosarcoma and reticulosarcoma), Kaposi's sarcoma in AIDS, melanoma, malignant pleurisy (as sclerosing agent), ascites against malignant tumors.

Contraindications:

- Hypersensitivity to bleomycin;

- dRespiratory failure (pulmonary fibrosis chronic interstitial pneumonia);

- dCompensated heart failure;

- tsevere kidney failure;

- bPregnancy and the period of breastfeeding.

Carefully:

Oppression of bone marrow hematopoiesis, concomitant or previous radiation therapy, acute infectious or viral diseases, renal and / or hepatic insufficiency of mild or moderate severity, child and elderly.

Pregnancy and lactation:

Bleomycin is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Women of childbearing age should use reliable methods of contraception when using bleomycin.

Dosing and Administration:

Bleomycin can be administered intramuscularly, intravenously, subcutaneously, intraperitoneally or intrapleusively.

In each individual case, when choosing the dose and mode of bleomycin administration, you should use the literature data. Doses are calculated per unit of total surface area of the body.

Recommended doses:

- intramuscularly or subcutaneously (in 1-5 ml of water for injection or 0.9% solution of sodium chloride, alternating injection sites) at a dose of 10-20 units / m²once or twice a week;

- intravenously struino (in 5-10 ml of 0.9% solution of sodium chloride or water for injection in for 5-10 minutes) at a dose of 10-20 units / m² once or twice a week;

- intravenously in the form of a 6-24 hour infusion (in 200-1000 ml of 0.9% solution of sodium chloride) at a dose of 10-20 units / m² for 4-7 days every 3-4 weeks;

- intrapleurally and / or intraperitoneally (in 50-100 ml of 0.9% solution of sodium chloride after evacuation of the maximum possible amount of exudate) 60 units once.

Because of the increased risk of developing an anaphylactic reaction in patients with malignant lymphomas, the initial dose may be reduced (for example, up to 2-3 U / m²). In the absence of an acute reaction to the administration of the drug, further therapy can be continued in the usual dose.

The total cumulative dose of bleomycin should not exceed 400 units. Further continued introduction of the drug can be carried outonly after evaluation lungs.

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

Age (years)	Total dose	Weekly dose
80 and over	100 units	15 units
70-79	150-200 IU	30 units
60-69	200-300 IU	30-60 units
Less than 60	400 units	30-60 units

The introduction of bleomycin to children only on "vital" indicators,the dose should be determined from the calculation of the body surface.

In patients with impaired renal function The dose of bleomycin 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 delayed until the levels of creatinine are normalized.

When carrying out radiation therapy, the dose of bleomycin should be reduced, since irradiated tissues are more sensitive to the drug. Correction of a dose of a preparation should be carried out and in that event if bleomycin is used in combination with other chemotherapy drugs.

Side effects:

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

From the skin and skin appendages: dyskoratosis (thinning or thickening of the skin) in the region of the elbow or knee joints, palms, buttocks, scapula, hyperemia, rash, striae, hyperpigmentation, skin itching, deformity and fragility of nails, hyperesthesia of the skin and distal (nail) phalanges, hyperemia of fingertips, alopecia ,

On the part of the digestive system: anorexia, nausea, vomiting, diarrhea, stomatitis, weight loss (with prolonged use).

Allergic reactions: urticaria, anaphylactic reactions, idiosyncrasy (lowering blood pressure, confusion, fever, chills, wheezing).

From the nervous system: headache, dizziness, fainting.

Other: an increase in body temperature and chills (usually 2-6 hours after the first injection of bleomycin,injecting significantly decreases), vascular disorders (including cerebral arteritis, thrombotic microangiopathy, myocardial infarction, Raynaud's syndrome), pleuropericarditis, fatigue, pain in the field of tumor formations, changes in functional tests of the liver and kidneys, insignificant suppression of bone marrow function, conjunctivitis , vulvitis and other manifestations of the mucous membranes (usually 2-5 weeks after the start of therapy after reaching total doses of 150-200 units).

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

Overdose:

Symptoms: arterial hypotension, fever, rapid pulse, broncho-pulmonary complications and general symptoms of anaphylactic shock.

Treatment: symptomatic. With complications from the bronchopulmonary system, glucocorticosteroids and broad-spectrum antibiotics are used.

Interaction:

When concomitantly administered bleomycin with carmustine, mitomycin, cyclophosphamide and methotrexate, filgrastim and other cytokines, as well as previous or current radiotherapy for the thoracic region, the risk of developing pulmonary toxicity increases.

Patients treated with bleomycin have an increased risk of pulmonary toxicity when they inject oxygen during anesthesia during surgery. Such patients are recommended to reduce the concentration of oxygen in the process and after the operation.

In patients undergoing combined treatment with bleomycin and preparations from the class of vinca alkaloids, the risk of vascular disorders increases, as a result of which Raynaud's syndrome may develop: the ischemia of the peripheral parts of the body, leading to necrosis of these areas (fingers and toes and nose).

With the simultaneous use of bleomycin with clozapine, the risk and severity of hematologic toxicity increases as a result of the additive effect.

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

Special instructions:

- Treatment with the drug should be monitoreddoctor with an experience use of antitumor drugs.

- Patients undergoing bleomycin treatment should regularly perform pulmonary function tests as well as chest radiography. The toxicity of bleomycin increases when the cumulative dose of 400 DB (225 U / m²), however, the toxic dose can be significantly lower in elderly patients, in patients with renal dysfunction, with lung diseases in history, in the case of lungs and smoking previously performed.

- Sensitivity to bleomycin is increased in elderly patients.

- When coughing, dyspnea, wheezing, or radiographic signs of interstitial pneumonia occur, bleomycin should be discontinued until the toxic effects of the drug are eliminated. If necessary, antibiotics and glucocorticosteroids should be prescribed.

- With ulcerative stomatitis and allergic rash treatment is discontinued.

- To stop fever, you can take antipyretics.

- The concentration of bleomycin in the blood plasma increases sharply when the drug is administered to a patient with impaired renal function.

- During treatment with bleomycin and at least 3 months after, reliable methods of contraception should be used.

- The usual precautions should be observed during preparation and administration. If the product gets on the skin or mucous membrane, these places should be rinsed with water for a long period of time.

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

- For the introduction use freshly prepared solutions.

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

Considering that dizziness, confusion, nausea, and fainting may occur in patients with Blaomycin-RONTS®, during the drug administration it is necessary to refrain from controlling the vehicles and mechanisms and performing other works that require concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Lyophilizate for solution for injection, 15 units.

Packaging:

To 15 units in a bottle of colorless glass, corked bromobutyl Rubber for running in aluminum cap or aluminum cap with plastic insert.

1 bottle with instructions for use in a cardboard box.

Storage conditions:

In a dry, dark place at a temperature of 2 to 8 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002815

Date of registration:13.01.2015 / 14.04.2016

Expiration Date:13.01.2020

The owner of the registration certificate:RNTS named after N.N. Blokhin RAMS RNTS named after N.N. Blokhin RAMS Russia

Manufacturer: & nbsp

RNTS named after N.N. Blokhin RAMS Russia

Information update date: & nbsp18.02.2017

Illustrated instructions

Instructions

Bleomycin-RONTS® (BLEOMYCIN-RONC®)