Index of drugs

Squamous cell carcinoma (SCC) of the head and neck, external genitalia and cervix. Hodgkin's disease. Non-Hodgkin's lymphomas of medium and high malignancy in adults. Testicular cancer (seminomatous and non-seminomatous). Pleural effusion in the pleural cavity of the tumor origin via the intrapleural route. Bleomycin is almost always given in combination with other cytostatic drugs and / or radiotherapy.

1 vial contains 15,000 IU bleomycin in the form of sulphate.

Cytostatic antibiotic. Bleomycin works by intercalating into single and double strands of DNA, resulting in single and double strand breaks, which inhibits division, cell growth, and DNA synthesis. To a lesser extent, bleomycin also affects RNA and protein synthesis. The most important factor affecting tissue selectivity of bleomycin is the difference in the lack of intercellular activity. Cells in the G2 phase and M phase of the cell cycle are the most sensitive. However, over the last decade, more and more evidence has been collected that points to RNA as yet another potential molecular target. Squamous cells, in which the level of bleomycin hydrolysis is usually negligible, display high sensitivity to bleomycin. In sensitive tissues and normal cancer tissues, frequent results will be chromosomal abnormalities, such as fragmentation, chromatid disruption or translocation. Tumors with a higher degree of differentiation usually respond better than anaplastic tumors. After intraperitoneal or intraperitoneal administration, bleomycin is absorbed systemically. After intrapleural administration, approximately 45% is absorbed in the bloodstream. After intramuscular injection 15 x 10³ IU in humans, a maximum plasma concentration of 1 IU / ml was reached 30 min after administration. After intravenous injection 15 x 10³ j.m./m² in humans, the maximum plasma concentration was 1-10 IU / ml. After a continuous infusion of 30 x 10³ IU bleomycin daily for 4 to 5 days mean steady-state plasma concentration was 1 to 3 IU / ml. After parenteral administration, bleomycin is distributed primarily in the skin, lungs, kidneys, peritoneum and lymph. The bone marrow is present only in low concentrations. If the meninges are intact, bleomycin can not penetrate the blood-brain barrier. Bleomycin crosses the placenta. In plasma, bleomycin hardly binds to plasma proteins. Inactivation of bleomycin occurs through enzymatic degradation through bleomycin hydrolysis mainly in the plasma, liver and other organs, to a lesser extent in the skin and lungs. After a single intravenous bolus injection, the clearance is rapid and there are two elimination phases. A short initial phase (vol_0,5α; 24 min), followed by a longer final phase (vol_0,5β; 2-4 h). After a single intravenous injection (bolus) of 15 x 10³ j.m./m² the maximum plasma concentration is 1 to 10 μg / ml. After a continuous intravenous infusion, the elimination half-life may extend to about 9 hours. About 2/3 of the administered dose of bleomycin is excreted unchanged in the urine. The rate of excretion is significantly influenced by renal function. Plasma drug concentrations are very elevated when given in normal doses in patients with impaired renal function. Bleomycin can not be removed by dialysis.

Hypersensitivity to bleomycin. Patients with acute pulmonary infection or a severe reduction in lung function. Patients with bleomycin-related pneumotoxicity or reduced lung function that may be indicative of bleoticin-related pneumotoxicity. Patients with ataxia-telangiectasia. Breast-feeding.

In patients treated with bleomycin and up to 8 weeks after the end of therapy, regular lung function tests (in particular measurements of carbon monoxide diffusion capacity and vital capacity) and chest X-ray should be performed. While chest irradiation, the chest test or chest X-ray should probably be performed more frequently.If unexplained coughing, shortness of breath, lung crackling or diffuse retroperitoneal changes in the chest X-ray occurs, treatment with bleomycin should be discontinued immediately, until bleomycin-related pneumotoxicity is ruled out as the likely cause of the symptoms. It is recommended to administer antibiotics and, if necessary, corticosteroids (eg Hydrocortisone administered intramuscularly in the form of sodium succinate 100 mg daily for 5 days followed by Prednisolone 10 mg twice daily). In the case of lung damage caused by the use of bleomycin, bleomycin should be completely dispensed with. Although bleomycin pneumotoxicity increases markedly at a cumulative dose of 400 U, it may also occur at a much lower dose, in particular in elderly patients, patients with impaired liver or kidney function, patients with a history of pulmonary disorder, prior lung irradiation, and patients receiving oxygen . Lung function tests using 100% oxygen should not be used in patients who have been treated with bleomycin; Pulmonary function tests using 21% oxygen are recommended. Exposure to long-term effects of very high oxygen concentrations is a known cause of lung damage, whereas after bleomycin administration, lung damage can occur at oxygen concentrations lower than those usually considered safe. Optimal intraoperative guidance of the patient therefore requires the lowest fraction of inhaled oxygen (FIO2) compatible with the proper administration of oxygen (oxygenation). Extreme care should be taken with bleomycin in patients with lung cancer, as these patients have an increased incidence of pneumotoxicity. Caution should be exercised in patients with impaired renal function, these patients have very high plasma levels. Bleomycin pneumotoxicity is thought to be dose-dependent with a definite increase when the total dose of 400 x 10 is exceeded.³ IU Total doses exceeding 400 x 10³ IU should be administered with extreme caution.

Bleomycin should therefore not be used during pregnancy unless absolutely necessary. Animal studies showed reproductive toxicity. Based on the results of animal tests and the pharmacological effectiveness of the drug, there is a potential risk of embryo and fetal anomalies. If a patient becomes pregnant during treatment, it should be informed of the existing risks to the unborn child and carefully monitored. The possibility of consulting a specialist in the field of genetics should be considered. Genetic counseling is also recommended for patients who want to have children after treatment. Due to the possibility of very harmful effects on the newborn baby, breast-feeding is contraindicated during treatment with bleomycin. Patients, both male and female, should use appropriate measures to prevent pregnancy up to 3 months after the end of treatment. Due to the possibility of irreversible infertility caused by the use of bleomycin, advice on freezing sperm should be sought before starting treatment.

Like most cytostatics, bleomycin can cause both acute and delayed toxic effects. Very common: interstitial pneumonitis (affects about 10% of patients, may occur during or in incidental cases after bleomycin treatment, may lead to pulmonary fibrosis and death in approximately 1% of patients receiving bleomycin); damage to mucous membranes or skin (up to 50% of patients), ulceration of mucous membranes (may be exacerbated if bleomycin is given in combination with radiotherapy or other preparations that have toxic effects on mucous membranes), nausea, vomiting, loss of appetite, drop body weight and inflammation of mucous membranes (inflammation of the mucosa, inflammation of the mouth); pigmentation of flagellate (occurs in 8-38% of patients, these changes depend on the dose and appear in the form of linear hyperpigmentation, which is accompanied by pruritus, thickening, hyperkeratosis, redness, sensitivity and swelling of the fingertips, erythema and rash mainly on the hands and feet , dermatoses, blisters, changes on nails, swelling in pressure-sensitive areas such as elbows and hair loss are rarely severe and usually disappear after completion of treatment). Common: severe hypersensitivity / idiosyncratic reactions similar to clinical anaphylaxis (observed in approx.1% of patients, mainly in patients with lymphoma; anaphylactic reactions may be immediate or delayed for several hours and usually occur after the first or second dose; it consists of hypotension, confusion, fever, chills and wheezing, and can be fatal); fever (may occur 2-6 h after the first injection, the incidence of fever decreases with subsequent injections); after intravenous or intranasal administration, pain at the injection site or within the tumor may occur. Uncommon: slight suppression of the bone marrow (mild thrombocytopenia may occur, which quickly disappears after treatment). Rarely: myocardial infarction, coronary heart disease; damage to blood vessels (eg myocardial infarction, coronary heart disease, impaired blood flow in the brain, inflammation of blood vessels in the brain, so-called hemolytic-uremic syndrome); Cases of hypotension, very high fever and drug-induced death have been reported after a Acute reactions with hypererpyxia and cardiopulmonary collapse were reported after intravenous injection of higher than recommended doses. In addition, low blood pressure, local thrombophlebitis and venous blockage may occur after intravenous administration. In patients receiving bleomycin, scleroderma, paresthesias and hyperalgesia, muscle and limb pain and cases of Raynaud-like syndrome have also been reported as ischaemia that may lead to necrosis of the peripheral parts of the body. Hypodermic events treated with high initial doses have reported cases of hypotension episodes. During and immediately after the completion of chemotherapy with bleomycin, aneuploid spermatozoa (with an incorrect number of chromosomes) may appear.

Intravenously, intramuscularly, intrapleural, intraperitoneal, intra-arterial or subcutaneous. Sometimes local injection may be indicated directly into the tumor. The medicine should only be prescribed in IU. (do not use the conversion factor per mg of dry matter, due to the risk of overdose). The dose and intervals between injections depend on the indication, method of administration, age and condition of the patient. It is recommended to adjust the dose to the patient's body surface.
Squamous cell carcinoma. Intramuscularly or by intravenous injection: 10-15 x 10³ j.m./m² 1 or 2 times a week. Treatment may be continued in the following weeks or, more commonly, at intervals of 3-4 weeks, up to a total cumulative dose of 400 x 10³ IUIntravenous infusion: 10-15 x 10³ j.m./m² daily, lasting 6-24 h in 4-7 consecutive days, every 3-4 weeks. The occurrence of stomatitis is the most characteristic symptom allowing to determine individual patient tolerance in relation to the maximum dose.Testicular cancer. Intramuscularly or by intravenous injection: 10-15 x 10³ j.m./m² 1 or 2 times a week. Treatment can be continued in the following weeks or, more frequently, at intervals of 3-4 weeks, until the total cumulative dose of 400 x 10 is reached.³ IUIntravenous infusion: 10-15 x 10³ j.m./m² daily, lasting 6-24 hrs for 5-6 consecutive days, every 3-4 weeks. The occurrence of oral inflammation is the most characteristic symptom allowing to determine the individual patient's tolerance with respect to the maximum dose.Malignant lymphoma (Hodgkin and non-Hodgkin). As a monotherapy, the recommended dose is 5-15 x 10³ IU 1 to 2 times a week, until the total dose of 225 x 10³ IU Due to the increased risk of anaphylactic reaction in patients with lymphoma, administration of the drug should be started at lower doses (eg 2 x 10³ IU). If no severe reactions occur within 4 hours of observation, the drug may be administered according to the normal dosing schedule.Intrapleural treatment of pleural effusion in the pleural cavity. Monotherapy with bleomycin in a single dose up to 60 x 10³ IU intrapleural. After drainage of the pleural cavity, 60 x 10³ IU bleomycin dissolved in 100 ml of saline solution is infused through a drainage needle or cannula. After administration of the drug, the drain needle or cannula are removed. Administration of the drug can be repeated if necessary. Approx. 45% of bleomycin will be absorbed, which should be taken into account when setting the total dose (body surface area, kidney function, lung function).Combination therapy: detailed information on the dosage regimens used in the individual indications for use can be found in the current literature. The use of bleomycin in combination therapy may require adjusting its dose. When using bleomycin in combination with radiotherapy, it may be necessary to reduce the dose of bleomycin. Bleomycin is often used as one of the components in combination chemotherapy regimens (eg for the treatment of squamous cell carcinoma, testicular cancer and lymphoma). The toxic effects of bleomycin on mucous membranes should be taken into consideration when selecting and setting dosing of products of similar toxicity, while they are used in combination therapy regimens.
Elderly patients. The total dose of bleomycin in elderly patients should be reduced as follows: age ≥ 80 years - weekly dose is 15x10³ j.m., total dose 100 x 10³ J. M .; 70-79 years - weekly dose 30 x 10³ j.m., total dose 150-200 x 10³ J. M .; 60-69 years - 30-60 x 10³ IUChildren: Until more data are available, bleomycin should only be administered to children in exceptional cases and in specialist centers. The dose should be determined based on the recommended adult dose and adjusted to the patient's area and weight.Reduced renal function: there are no guidelines for detailed dose adjustments in these patients, although the following is suggested - patients with moderate renal impairment (GFR 10-50 ml / min) should receive 75% of the usual dose administered at regular intervals, and patients with severe heart failure kidneys (GFR <10 ml / min) should receive 50% of the usual dose administered at normal intervals. No dosage adjustment is necessary for patients with GFR> 50 ml / min.
Method of administration. Intramuscular and subcutaneous injection: dissolve the required dose in a maximum of 5 ml of a suitable solvent, such as a 0.9% sodium chloride solution. If pain occurs at the injection site, a local anesthetic (1% Lidocaine solution) can be added to the solution ready for administration. Intravenous use: dissolve the required dose in 5-1000 ml of 0.9% sodium chloride solution and slowly inject or add to the current infusion. Intra-arterial administration: slow infusion with physiological saline. Intraplear injection: dissolve 60 x 10³ IU in 100 ml of 0.9% sodium chloride solution. Local / tumor injections: bleomycin is dissolved in 0.9% sodium chloride solution to a concentration of 1-3 x 10³ j.m./ml of the solution.