Index of drugs

Soft tissue and bone tissue sarcomas, Hodgkin's disease, non-Hodgkin's lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, thyroid cancer, breast cancer, ovarian cancer, bladder cancer, small cell lung cancer, neuroblastoma. The use of the drug has clear benefits in the treatment of: multiple myeloma, endometrial cancer, cervical cancer, Wilms tumor, head and neck tumors, gastric cancer, pancreatic cancer, prostate cancer, testicular cancer and liver cancer.

1 ml of concentrate contains 2 mg of doxorubicin hydrochloride.

Cytotoxic antibiotic from the anthracycline group with anticancer activity. There is no unambiguous position regarding the antitumor mode of action of the drug; 3 basic mechanisms were proposed: DNA inserts, membrane binding and metabolic activation through reduction. After intravenous administration, rapid plasma clearance and significant binding to tissues are found. The degree of binding to plasma proteins is 50-85%. The drug does not penetrate the blood-brain barrier. It is partially metabolised, mainly to doxorubicinol and to a lesser extent to the aglycone and coupled with glucuronate or sulphate. The main route of excretion is excretion with bile and faeces, about 10% excreted by the kidneys. T_0,5 the elimination phase is about 30 hours.

Hypersensitivity to doxorubicin, drugs with a similar chemical structure or to any of the excipients. Doxorubicin is contraindicated in patients with pronounced bone marrow suppression (eg following previous anticancer treatment), in patients with pre-existing or current severe heart failure and in patients who have previously received the maximum cumulative dose of doxorubicin or daunorubicin. The presence of ulceration of the mucous membrane of the cheeks. This symptom can be preceded by a feeling of burning the mucous membrane of the cheeks. If it occurs, it is not recommended to administer the medicine. Pregnancy and breast-feeding. Doxorubicin should not be used intravesically in the treatment of bladder cancer in patients with urethral stricture who can not enter the catheter. Do not attempt intravesical use in patients with invasive tumors that infiltrate the bladder wall, urinary tract infection or inflammation of the bladder.

If extravasation occurs, the injection should be stopped immediately and the medicine should be given to another vein. In the place of extravasation, use ice packs and appropriate treatment. The use of an anthracycline increases the risk of dose-related cumulative cardiomyopathy (the cumulative dose should not exceed 450-550 mg / m²). Symptoms may appear suddenly after many months or years after the end of treatment, without previous ECG changes. The risk of heart failure in patients with malignancies who have been treated with doxorubicin is maintained throughout their lives. Heart failure caused by the drug may be resistant to traditional methods of treatment. The risk of cardiotoxicity is higher in patients who have undergone irradiation of the mediastinum or pericardium, have received other anthracylkines and / or anthracenediones, in patients with a history of cardiac disease, in the elderly (≥70 years) and in children under 15 years of age. Special care should be taken in patients with heart disease such as recently-experienced myocardial infarction, heart failure, cardiomyopathy, pericarditis, arrhythmias and in patients who have received other cardiotoxic agents (eg cyclophosphamide). ECG changes such as a decrease or a negative T wave, ST segment depression or arrhythmia are not indications for discontinuation of therapy; persistent reduction of QRS amplitude and extension of the systolic period are considered to be more potent indications of cardiotoxicity; in the case of a reduction in the voltage of the QRS complex by 30% or a truncation fraction by 5%, the administration of doxorubicin should be discontinued.An absolute decrease in the LVEF value by> 10% or a reduction below 50% in patients with normal baseline LVEF is a symptom of cardiac dysfunction - further treatment should be considered. Doxazubicin should not be initiated or continued in cases where the number of polymorphonuclear granulocytes is less than 2000 / mm³. In the treatment of acute leukemias, this limit can be set at a lower level. Severe bone marrow suppression may lead to hemorrhage or superinfection and is an indication for dose reduction or discontinuation of doxorubicin. Due to the risk of immunosuppression, measures to prevent secondary infections should be used. Caution should be exercised in patients with impaired hepatic function. In children, there is an increased risk of cardiotoxicity, especially delayed cardiotoxicity; should be expected to have bone marrow toxicity (nadir after 10-14 days); in children, improvement is fast, due to the large reserve of bone marrow.

The drug should not be used during pregnancy and breast-feeding. Men and women should use effective contraception during doxorubicin treatment and for at least 3 months after treatment.

Blood and lymphatic system disorders - very common: bone marrow suppression (transient leucopenia, anemia and thrombocytopenia), nadir occurs after 10-14 days after administration of the drug. Gastrointestinal disorders - very common: nausea, vomiting, mucositis (oral mucositis, proctitis) and diarrhea may occur after 5-10 days after administration of the drug; damage to the gastrointestinal tract can lead to ulceration, hemorrhage or perforation, there is a risk of secondary infection, inflammation of the mucous membrane of the vagina, rectum and esophagus. Skin and subcutaneous tissue disorders - very often: reversible balding (in the majority of patients), hyperpigmentation of nail beds, formation of furrows on the skin, separation of nails from the placenta. Extravasation of the drug at the infusion site may cause local pain, irritation, inflammation, thrombophlebitis, severe skin ulcer, skin necrosis. Hypersensitivity reactions have been reported sporadically: rash, pruritus, urticaria, angioneurotic edema, fever, anaphylactic reaction. Doxorubicin has an effect and intensifies the normal reaction of tissues to irradiation. After some time after the end of the irradiation, secondary reactions may occur ("reminder reactions"). Cardiac disorders - often and very commonly: cardiotoxic effects may occur as cardiac arrhythmia immediately after administration. ECG changes (flattening of the T wave and ST segment depression) may take up to 2 weeks after administration. The risk of cardiomyopathy increases when increasing the dose. Cardiotoxic effects may be delayed by several weeks, months or years after completion of therapy. Hepato-biliary disorders - common: slight, transient increase in liver enzymes. Concomitant irradiation of the liver may cause severe hepatotoxic effects, sometimes leading to liver cirrhosis. Renal and urinary disorders - often after intravesical administration: haematuria, irritation of the bladder and urethra, painful urination with drops, pollakiuria (these reactions are usually moderate and last shortly). Intravesical administration may cause hemorrhagic cystitis, which may lead to a reduction in bladder capacity. Doxorubicin causes a red urine. Benign and benign tumors (including cysts and polyps) - rarely: in patients treated with doxorubicin in combination with anticancer drugs that damage DNA, the occurrence of secondary acute myeloid leukemia with or without leukaemic phase has been reported. There are also cases with a short grace period (1-3 years). In addition, rarely may occur: conjunctivitis, tearing, thrombophlebitis; if the drug is administered too quickly, redness of the face may occur.

Doxorubicin treatment should only be used by a physician experienced in the use of chemotherapy. It is recommended to hospitalize the patient at least at an early stage of treatment.Intravenous use. It can be given by injection into a vein over 2-5 minutes or as an intravenous infusion with 0.9% NaCl, 5% Glucose or a solution for infusion containing NaCl and glucose. Adults.Monotherapy. Dosage depends on the type of tumor, heart and liver function and concomitant use of chemotherapy. Recommended dose: 60-75 mg / m² intravenous infusion every 3 weeks Alternative: 20 mg / m² for 3 consecutive days once every 3 weeks. The maximum cumulative dose is 550 mg / m². It was found that doxorubicin weekly is as effective as every 3 weeks, with less cardiac toxicity. A dose of 20 mg / m is recommended² every week, however, the objective response to treatment was obtained at doses of 6-12 mg / m². Combination therapy. When used with cytotoxic drugs with similar toxic effects, the dose should be reduced. If the patient is treated by mediastinal irradiation or has a cardiac disease or is taking oncological drugs with cardiotoxic effects, not belonging to anthracyclines, a maximum cumulative dose of 450 mg / m is recommended.². In patients withimpaired liver function dose should be reduced: when the concentration of bilirubin in the blood is 12-30 mg should be used 1/2 dose; when serum bilirubin is above 30 mg, 1/4 doses should be used. On the wholeimpaired renal function does not require dose reduction. In patients withincreased risk of cardiotoxicity instead of injection, 24 h of the infusion should be considered. Before each treatment cycle, the ejection fraction should be measured. The cumulative dose of 450-550 mg / m should not be exceeded² during the patient's life. In patients with a history of cardiac or cardiac or mediastinal radiotherapy, do not exceed the cumulative dose of 400 mg. In combination with other oncological preparations, doxorubicin is used at doses of 50-75 mg / m². Lower doses should be used in children due to the greater risk of cardiotoxicity, especially delayed cardiotoxicity. It is recommended to carry out cardiac check-ups. It is expected to have bone marrow toxicity with minimal haematological parameters (nadir) after 10-14 days from the start of therapy. In children, the improvement is usually fast due to the large bone marrow reserve in comparison to adults.Intravesical administration. Superficial bladder cancer and bladder cancerin situ: 50 mg in 50 ml of physiological solution, into the bladder using a sterile catheter. Initially, once a week, then once a month. Treatment lasts 6-12 months. After intravesical administration, there are no restrictions on the maximum cumulative dose. Do not administer the drug in a long-term infusion. The precipitation of doxorubicin has been reported when co-administered with Heparin and 5-fluorouracil - do not mix with other drugs.