Index of drugs

Soft and bone tissue sarcomas, Hodgkin's disease, non-Hodgkin's lymphoma, breast cancer, ovarian cancer, bladder cancer, lung cancer, rectal cancer, stomach cancer.

1 vial contains 50 mg epirubicin hydrochloride. 1 ml solution for injection and inf. and to be served. into the bladder contains 2 mg of epirubicin hydrochloride.

A cytostatic agent from the group of anthracycline antibiotics. Epirubicin is a non-specific medicine for the cell cycle. It works in the S and G2 phases of the cell, and at higher concentrations it can also affect the G1 and M phase. The mechanism of action is the insertion of epirubicin between nucleotide pairs in the double helix of DNA. There is a local development and change of the conformation of the helicopter or its disruption and fragmentation, which consequently leads to the inhibition of DNA synthesis. Epirubicin administered intravenously quickly penetrates organs and tissues, reaching relatively high concentrations in the lymph nodes, healthy and cancerous tissues of the stomach, gall bladder tissues, liver metastases and in red blood cells. Mean values ​​of drug concentration are observed in nervous, muscular tissue, fallopian tube, lung cancer and healthy and cancerous tissues of the endometrium. The antibiotic does not penetrate into the cerebrospinal fluid. Epirubicin is metabolised in the liver to the main biologically active metabolite - glucuronides, epirubicin and epirubicinol (a cytotoxic compound). Glucuronidation of epirubicin proceeds differently than doxorubicin, which results in faster excretion of epirubicin and its lower toxicity in comparison with doxorubicin. High levels of metabolites appear very quickly in the blood and tissues. In patients with impaired liver function, the metabolism of epirubicin differs from doxorubicin, slowing down the drug and consequently increasing its accumulation in blood serum and tissues. 40% of the administered dose is excreted in the bile within 72 h. By the kidneys, 9-10% of the administered dose is excreted within 48 hours.

Hypersensitivity to epirubicin, drugs with a similar chemical structure or to any of the excipients. Patients with markedly inhibited bone marrow function (eg as a result of previous anticancer treatment). Patients with pre-existing or severe heart failure. Patients who have previously received the maximum cumulative dose of other anthracyclines, such as: doxorubicin or daunorubicin. Pregnancy and breast-feeding. The drug should not be used intravesically in the treatment of bladder cancer in patients with urethral stricture who can not enter the catheter. In addition, intravesical medications should not be attempted in patients with invasive tumors that infiltrate the bladder wall, urinary tract infection or inflammation of the bladder. The drug should not be used intramuscularly, subcutaneously, intrathecally or in long-term infusion.

The drug should only be used under the supervision of a doctor with experience in the use of chemotherapy. It is recommended to stay in the hospital at least during the first phase of treatment, as close observation and laboratory tests are necessary. Before and during the treatment, cardiac function tests should be performed (ECG should be performed before and after each administration) and liver (AST, ALAT, alkaline phosphatase and bilirubin) as well as haematological tests and determination of uric acid in the blood (appropriate fluid intake min 3 l / m²/ day, if necessary, you can give allopurinol). ECG changes such as a decrease or a negative T wave, ST segment depression or arrhythmias are usually symptoms of acute but transient toxic effects - they are not considered indications for treatment discontinuation. Persistent QRS amplitude reduction and extension of the systolic period are considered to be more potent indications of anthracycline cardiotoxicity. If the QRS band voltage is reduced by 30% or the fractional shortening by 5%, epirubicin should be discontinued.The optimal method of predicting the occurrence of cardiomyopathy is the detection of decreased left ventricular ejection fraction (LVEF) by means of echocardiography or scintigraphy. The LVEF study should be performed prior to the use of epirubicin and should be repeated each time the Next cumulative dose of 100 mg / m²and in the event of any clinical symptoms of heart failure. It should be assumed that an absolute reduction of> 10% or a reduction below 50% in patients with normal baseline LVEF is a symptom of cardiac dysfunction - the possibility of further use of epirubicin in such patients should be carefully assessed. If extravasation occurs, stop the injection immediately and administer the medicine to another vein. The use of an anthracycline increases the risk of dose-related cumulative cardiomyopathy - the cumulative dose of epirubicin 450-550 mg / m should not be exceeded² (reducing the cumulative dose is the most important way to avoid the effects of cardiotoxic epirubicin). Cardiotoxic effects (symptoms: tachycardia, ECG changes or heart failure) may occur suddenly, many months or years after the end of treatment, without previous ECG changes - the risk of cardiotoxicity is greater in patients who have undergone irradiation of the mediastinum or pericardium, received other anthracyclines and / or anthracenediones, in patients with a history of cardiac disease, in the elderly (≥ 70 years old) and in children under 15 years of age. The risk of heart failure in patients with malignant tumors who have been treated with epirubicin is maintained throughout life and heart failure may be resistant to traditional therapies. Cardiotoxic effects may occur after administration of the drug at doses lower than the recommended cumulative limit dose. The total cumulative dose of epirubicin for a particular patient should include any previously or simultaneously used drugs or therapies with potential cardiotoxicity or treatment regimens such as high dose cyclophosphamide, mitomycin C or dacarbazine, other anthracyclines, e.g. daunorubicin and mediastinal irradiation or pericardium. Special care should be taken in patients with heart disease such as a recent myocardial infarction, heart failure, cardiomyopathy, pericarditis or arrhythmias, and in patients who have received other cardiotoxic agents such as cyclophosphamide.

Epirubicin is contraindicated for use during pregnancy and breastfeeding. Animal studies have shown teratogenic and embryotoxic effects. Epirubicin is excreted in human milk.

Very common (> 10%): bone marrow suppression includes transient leukopenia, anemia and thrombocytopenia (nadir occurs after 10-14 days after drug administration); nausea, vomiting, mucositis (oral mucositis, esophagitis, proctitis, vaginitis), diarrhea (may occur after 5-10 days after administration of the drug), damage to the gastrointestinal tract that can lead to ulceration, haemorrhage or perforation; reversible alopecia, alopecia, hyperpigmentation of nail bearings, formation of furrows on the skin, separation of nails from the placenta. Often - very common (> 1% -> 10%): cardiac arrhythmias (changes in ECG, including flattening of the T wave and ST depression may last up to 14 days after drug administration). Common (> 1% - <10%): slight, transient increase in liver enzymes; after intravesical administration, hematuria, irritation of the bladder and urethra, painful urination with drops and pollakiuria, sometimes haemorrhagic cystitis may occur. Rarely (> 0.01 - <0.1%): conjunctivitis, tearing, thrombophlebitis; secondary myeloid leukemia with or without leukaemic phase (in patients treated with epirubicin in combination with antineoplastic drugs damaging DNA, there are cases with a short latency period - 1-3 years). Hypersensitivity reactions (skin reactions - rash, pruritus, urticaria, angioneurotic edema, fever, anaphylactic reaction) have been reported sporadically. Epirubicin has a very strong irritant effect in cases of extravasation at the infusion site, local pain, irritation, inflammation, thrombophlebitis and even severe ulceration and necrosis of the skin may occur.Epirubicin influences and intensifies the normal tissue reaction to irradiation, after some time after the end of the irradiation secondary reactions may occur. If the drug is injected too quickly, redness may appear on the face.

Intravenously.Adults. monotherapy: the most often recommended dose is 60-90 mg / m² Depending on the patient's condition, the dose may be repeated at 21-day intervals. The total dose of one cycle can be divided into 2 or 3 consecutive single doses. High doses: monotherapy of small-cell lung cancer - 120 mg / m at the beginning of treatment² pc. every 3 weeks; monotherapy of non-small cell lung cancer andadenocarcinoma - 135 mg / m is given at the beginning of treatment² pc. once or 45 mg / m² pc. for 3 consecutive days every 3 weeks. Patients with impaired bone marrow function after previous chemotherapy, radiotherapy or elderly patients: 60-75 mg / m monotherapy during standard treatment and 105-120 mg / m² when using high doses); the total dose can be divided and administered for 2-3 days.Combination therapy: the dose should be reduced when administering the drug together with other cytotoxic medicines with similar toxic effects; the total dose of epirubicin (also including other anthracyclines: daunomycin, doxorubicin, idarubicin) is 900-1000 mg / m² pc. (the total dose should be treated as the sum of doses used throughout life). Patients with impaired liver function: the dose should be reduced depending on the concentration of bilirubin - bilirubin 1.4-3.0 mg / 100 ml: 50% of the normal dose; > 3.0 mg / 100 ml: 25% of the normal dose. Patients with renal impairment: no dose reduction is required. Patients at risk for cardiac dysfunction: 24 h of the infusion should be considered; the 450-550 mg / m dose should not be exceeded² pc, accumulated over the life of the patient. In patients with pre-existing cardiac disease or after radiotherapy of the heart or mediastinum, cumulative doses> 400 mg / m should be avoided² pc. In combination with other oncological preparations, epirubicin is used at doses of 50-75 mg / m² pc.ChildrenThe dose should be reduced due to the increased risk of cardiotoxicity (especially delayed cardiotoxicity). Bone marrow toxicity should be expected, with minimal haematological parameters (nadir) 10-14 days after the start of therapy. In children, the improvement usually occurs quickly due to the large reserve of bone marrow compared to adults.
Solution for injection and infusion and for administration to the bladder.Superficial bladder cancer and bladder cancerin situ: a dosage of 50 mg in a 50 ml solution is recommended physiological inside the bladder using a sterile catheter. The patient should not take any liquids 12 h before the procedure, and during the procedure should lie and change the body position by 1/4 turn every 15 minutes. The medicine should be left in the bladder for about 1 hour. Initially, the medicine is given once a week and then once a month. The optimal duration of treatment has not been determined so far; the range is 6-12 months. After intravesical administration, there are no restrictions on the maximum cumulative dose because the systemic absorption of epirubicin is negligible. In the case of inflammation of the bladder, the dose may be reduced and administered 30 mg / 50 ml and for treatmentcarcinoma in situ increase to 80 mg / 50 ml.
It should be given by injection into a vein lasting not less than 3-5 minutes or by intravenous infusion with 0.9% sodium chloride, 5% Glucose or a drip into a vein containing sodium chloride and glucose. The drug should not be mixed with other preparations.