Epirubicin - instructions for use, dose, side effects, contraindications

Antitumor agent from the group of anthracycline antibiotics. The mechanism of action is associated with blockade of the matrix activity of DNA in DNA polymerase systems and DNA-dependent RNA polymerase, inhibition of the synthesis of nucleic acids.

Pharmacokinetics:

After intravenous administration to patients with normal liver and kidney function, the pharmacokinetic parameters of epirubicin are described by a three-phase model with a very fast first and slow terminal phase. Epirubicin distributed in the tissues of the body; does not penetrate the blood-brain barrier.

The half-life in the terminal phase is about 40 hours. The total clearance is 0.9 l / min. Basically epirubicin is excreted with bile.

Indications:

Cancer of the breast, ovaries, stomach, liver, pancreas, bronchogenic lung cancer, colorectal cancer, non-Hodgkin's lymphomas, soft tissue sarcoma, osteogenic sarcoma, neuroblastoma, head and neck tumors.

ICD-10

II.C64-C68.C67 Malignant neoplasm of bladder

II.C50 Malignant neoplasm of breast)

II.C45-C49.C49 Malignant neoplasm of other types of connective and soft tissue

II.C40-C41.C41 Malignant neoplasm of bones and articular cartilages of other and unspecified sites

II.C40-C41.C40 Malignant neoplasm of bones and articular cartilages of extremities

II.C15-C26.C25 Malignant neoplasm of pancreas

II.C15-C26.C20 Malignant neoplasm of rectum

II.C15-C26.C16 Malignant neoplasm of stomach

II.C15-C26.C15 Malignant neoplasm of esophagus

II.C81-C96.C85.9 Non-Hodgkin's lymphoma, unspecified

II.C81-C96.C82.9 Follicular non-Hodgkin's lymphoma, unspecified

II.C81-C96.C81.0 Hodgkin's disease is lymphoid predominance

II.C81-C96.C90.0 Multiple myeloma

Contraindications:

Hypersensitivity, pregnancy, breast-feeding, children's age (safety and efficacy not established). For intravenous administration: severe myelosuppression, severe hepatic insufficiency, decompensated heart failure, severe arrhythmia, myocardial infarction (recently transferred), therapy with cumulative doses of anthracycline antibiotics in anamnesis. For introduction into the bladder: invasive tumors with penetration into the wall of the bladder, urinary tract infection, cystitis.

Carefully:

With caution apply for violations of the liver (in this case, the dose should be reduced).

Pregnancy and lactation:

Action category for the fetus by FDA - D. Contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Women of childbearing age should apply reliable methods of contraception during epirubicin therapy.

In experimental studies, the teratogenic, embryotoxic, effect of epirubicin was established.

Dosing and Administration:

Intravenously, in the cavity, intraarterially.Intravenous (within 3-5 minutes), with monotherapy injected at a dose of 60-90 mg / m² 1 time in 3 weeks. With bone marrow suppression, metastasis in the bone marrow, violations of liver function, the dose is reduced to 60-75 mg / m². The total dose per cycle can be divided and administered within 2-3 consecutive days.

With combined therapy with other antitumour agents, the dose is reduced.

Intravesical (through the catheter) with papillary-cell cancer of the bladder - 50 mg (in 25-50 ml of physiological solution) once a week, the course - 8 weeks. If the symptoms of local toxicity develop, the dose is reduced to 30 mg, with cancer in situ the dose can be increased to 80 mg, depending on the individual tolerability of drugs. To prevent recurrence of post-transurethral resection of superficial bladder tumors - 50 mg intravesical once a week for 4 weeks, then 1 time per month for 11 months at the same dose.

After intravesical administration, the drug should be retained in the bladder for 1 hour, after which the patient should empty the bladder.

Side effects:

From the side cardiovascular system and blood (hematopoiesis, hemostasis): Early (acute) cardiotoxicity (sinus tachycardia and / or nonspecific changes in ST-T wave in ECG. tachyarrhythmias, including ventricular arrhythmias and tachycardia and bradycardia, atrioventricular block and bundle branch block occurrence of these phenomena is not always a predictor of later delayed cardiotoxicity, they are rarely clinically significant, and usually does not require discontinuation of therapy later (delayed) cardiomyopathy:. decrease in left ventricular ejection fraction and / or development Saver ynoy heart failure (dyspnea, pulmonary edema, orthostatic edema, cardio and hepatomegaly, oliguria, ascites, pleural effusion, gallop rhythm), pericarditis / myocarditis. The most severe form of cardiomyopathy induced by anthracyclines, is a life-threatening congestive heart failure that is a toxicity that limits the total dose of the drug Thromboembolism, including thromboembolism of the pulmonary artery (in some cases, with a fatal outcome). bone marrow hypoplasia, leukopenia (is transient, reaching the maximum level after 10-14 days of treatment; normalization of leukocytes occurs to the 21st day), thrombocytopenia, anemia.

From the side organs of the digestive tract: gastrointestinal disorders (nausea, vomiting, diarrhea), anorexia, inflammation of the mucous membranes (stomatitis in the form of painful erosions, especially on the sides of the tongue and on the hyoid mucous membrane), hyperpigmentation of the oral mucosa, esophagitis, pain or burning sensation in the abdomen , erosion of the stomach, bleeding from the gastrointestinal tract, colitis, an increase in the total bilirubin content and activity of hepatic transaminases in the blood serum.

From the side genitourinary system: hyperuricemia, amenorrhea (after the end of the therapy, ovulation recovers, but premature menopause is possible), oligospermia, azoospermia (in some cases, the number of spermatozoa is restored to normal levels, which may occur after several years).

From the side skin integument: alopecia, rash, itching, skin hyperemia, hyperpigmentation of skin and nails, photosensitivity, hypersensitivity of irradiated skin areas.

Allergic reactions: fever, chills, hives, anaphylaxis.

Other: asthenia, conjunctivitis, keratitis, mucositis, flushing to the face, attachment of secondary infection, development of secondary acute lymphocytic leukemia or myeloleukemia, reddish urine color (1-2 days after treatment).

Local reactions: erythematous striation along the vein in which the infusion was performed, local phlebitis or thrombophlebitis, phlebosclerosis (more often with repeated injections into veins of small diameter). When the drug gets into the surrounding tissue - soreness, suppuration and necrosis of surrounding tissues.

With intra-arterial administration (in addition): ulcers of the mucous membrane of the stomach and duodenum (due to reflux of the drug in the gastric artery), narrowing of the bile ducts due to drug-induced sclerosing cholangitis.

When inserted into the bladder (optional): development of chemical cystitis (dysuria, polyuria, nocturia, painful urination, hematuria, discomfort in the bladder), necrosis of the walls and wrinkling of the bladder.

Overdose:

Symptoms: expressed myelosuppression (mainly leukopenia and thrombocytopenia), toxic effects from the gastrointestinal tract (mainly mucositis), acute complications from the heart.

Treatment: symptomatic, antidote is unknown.

Interaction:

With the simultaneous use of epirubicin with other antitumour agents, the toxic effect of other antitumor drugs is enhanced,especially myelotoxicity and effects on the gastrointestinal tract; with cardiotropic drugs and drugs with potential cardiotoxicity - increased risk of cardiotoxic action.

With simultaneous application with cimetidine, prolongation of epirubicin half-life is observed.

Epirubicin should not be administered in a single solution with heparin, other antitumor drugs, since precipitation occurs.

Special instructions:

The use of epirubicin should be carried out under the supervision of qualified physicians with experience in antitumor therapy, observing the established precautionary measures (using goggles, disposable gloves and masks) and destroying materials used for work and unused remnants.

The total exchange dose should not exceed 1000 mg / m².

Before the start of therapy and regularly during treatment, careful cardiomonitoring and monitoring of various laboratory parameters should be carried out. A systematic control of the cellular composition of the blood, the functions of the heart and liver, and the maintenance of urate in the plasma are necessary.A decrease in the voltage of QRS on the ECG is the first sign of myocardial damage.

If it is necessary to appoint patients of childbearing age, it is necessary to use reliable contraceptive measures.

Avoid contact with the skin and mucous membranes. In case of accidental ingestion of the drug on the skin, it is necessary to wash it thoroughly with plenty of water with soap, if it gets into the eyes - with saline solution.

If the solution of the drug has spilled, it is necessary to conduct treatment with a dilute solution of hypochlorite (using a well-adsorbing liquid material), then with water.

Instructions

Epirubicin (Epirubicinum)