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

Antitumor agent from the group of anthracycline antibiotics, has antimitotic and antiproliferative effect. The mechanism of action is to bind DNA and suppress the synthesis of nucleic acids. The cells are sensitive to the drug in the S- and G2-phases.

Pharmacokinetics:

V_d is 20-30 l / kg. Does not penetrate the blood-brain barrier. Biotransformation occurs in the liver with the formation of an active metabolite. Half-life for doxorubicin and doksirubitsinola varies from 20 to 48 hours. The deduced with bile as unchanged (about 40% for 5 days) and the kidneys in unchanged form and as metabolites (about 5-12% for 5 days).

Indications:

Soft tissue sarcoma, osteogenic sarcoma, Ewing's sarcoma, breast cancer, small cell lung cancer, thyroid cancer, malignant thymoma, esophageal cancer, hepatoblastoma, primary hepatocellular carcinoma, gastric cancer, pancreatic cancer, carcinoid, bladder cancer (treatment and prevention relapse after surgery),germ cell testicular cancer, ovarian cancer, neuroblastoma, trophoblastic tumor Wilms tumor, endometrial cancer, cervical cancer, prostate cancer, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, Hodgkin's disease, non-Hodgkin's lymphoma, Kaposi's sarcoma in AIDS, cancer of the adrenal glands, retinoblastoma.

ICD-10

XXI.Z80-Z99.Z80.1 In a family history, a malignant neoplasm of the trachea, bronchi, and lung

II.C73-C75.C73 Malignant neoplasm of thyroid gland

II.C73-C75 Malignant neoplasm of thyroid gland and other endocrine glands

II.C64-C68.C67 Malignant neoplasm of bladder

II.C64-C68.C64 Malignant neoplasm of kidney, except for renal pelvis

II.C60-C63.C61 Malignant neoplasm of prostate

II.C51-C58.C58 Malignant neoplasm of placenta

II.C51-C58.C53 Malignant neoplasm of cervix

II.C50.C50 Malignant neoplasm of breast

II.C50 Malignant neoplasm of breast)

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

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

II.C15-C26.C26 Malignant neoplasm of other and inaccurately indicated digestive organs

II.C15-C26.C25 Malignant neoplasm of pancreas

II.C15-C26.C16 Malignant neoplasm of stomach

II.C15-C26.C15 Malignant neoplasm of esophagus

I.B20-B24.B21 Disease caused by human immunodeficiency virus [HIV], manifested as malignant neoplasms

II.C81-C96.C92.9 Myeloid leukemia, unspecified

II.C81-C96.C92.0 Acute myeloid leukemia

II.C81-C96.C91.0 Acute lymphoblastic leukemia

XV.O00-O08.O01 Bumpy drift

II.C81-C96.C81 Hodgkin's disease [lymphogranulomatosis]

II.C81-C96.C82 Follicular [nodular] non-Hodgkin's lymphoma

II.C45-C49.C46 Kaposi's Sarcoma

II.C15-C26.C22.0 Hepatic cell carcinoma

Contraindications:

Pronounced leukopenia, anemia, thrombocytopenia; severe diseases of the cardiovascular system; acute hepatitis; pregnancy. Doxorubicin Do not use in patients who have received a full cumulative dose of daunorubicin, idarubicin and / or other anthracyclines and anthracenes.

Carefully:

They are used with caution in patients with heart diseases (including history), chickenpox (including recently transferred or after contact with the diseased), herpes zoster, other acute infectious diseases, gout or nephrolithiasis (including history), as well as in patients with ongoing mediastinal radiation therapy or receiving concomitantly cyclophosphamide.

They are used with caution in patients with an insufficient reserve of bone marrow, due to the age preceding the use of cytotoxic agents or radiation therapy.

Pregnancy and lactation:

The category of FDA recommendations is not defined. Penetrates through the placental barrier, is not detected in the amniotic fluid; in the fetal organs, the concentration is several times lower than in the mother's blood plasma. Possible development of fetal side effects observed in adults. When used in the II and III trimesters can be cardiotoxic for the fetus. It is recommended to avoid the use of antitumor, especially combined, chemotherapy in pregnancy, especially in the first trimester. In the presence of indications, it is necessary to relate the risk and benefit and take into account the mutagenic, carcinogenic and teratogenic potential of these agents.In view of the potential threat to the fetus (side effects, mutagenicity, carcinogenicity and teratogenicity), it is recommended that women of childbearing age during treatment with doxorubicin use contraceptives.

Doxorubicin and its metabolites are found in breast milk. If it is necessary to treat the drug, breastfeeding should be stopped, due to the development of immunosuppression in a newborn, mutagenic and carcinogenic effect.

Dosing and Administration:

Intravenously slow, intravesical. The dosage regimen is set individually, depending on the indications, the patient's condition and the treatment regimen used. Adults, intravenously - 60-75 mg / m² 1 every 3-4 weeks, or 25-30 mg / m² per day for 2-3 consecutive days every 3-4 weeks or 20 mg / m² per day once a week at the 1st, 8th and 15th days of the course. Break between courses - 3-4 weeks. Children - intravenously at a dose of 30 mg / m² per day for 3 days every 4 weeks.

The bladder is administered 30-50 mg once a week at intervals of 1 week to 1 month. When combined therapy - 25-50 mg / m² every 3-4 weeks. The course dose should not exceed 500-550 mg / m². When the number of leukocytes is less than 3,3-3,5 · 10⁹/ l and platelets less than 100-149 · 10⁹/ l dose reduced by 50 and 75% respectively.At a level of bilirubin 12-30 mg / ml and above 30 mg / l the dose is reduced by 50 and 75%, respectively.

Side effects:

On the part of the hematopoiesis system: thrombocytopenia, leukopenia, anemia.

From the cardiovascular system: cardiomyopathy, heart failure, arrhythmias. The cases of development of severe, life-threatening arrhythmias are described immediately or within a few hours after the administration of doxorubicin.

From the digestive system: stomatitis, esophagitis, abdominal pain, nausea, vomiting, diarrhea.

On the part of the reproductive system: azoospermia, amenorrhea.

Allergic reactions: urticaria, fever, anaphylactoid reactions.

Other: alopecia, hyperuricemia, nephropathy.

Local reactions: when small-diameter veins are introduced into the veins or when repeated introduction into the same vein, sclerosing the vessel; when extravasation - tissue necrosis.

Overdose:

Symptoms: increased toxic effects (inflammation of the mucous membranes, leukopenia, thrombocytopenia).

Treatment: therapy with antibiotics, transfusion of granulocyte mass, symptomatic treatment of mucosal inflammation.

Interaction:

Drugs that oppress hemopoiesis exacerbate thrombocytopenia and leukopenia, which are caused by doxorubicin.

When used simultaneously with hepatotoxic drugs (including methotrexate), the hepatotoxic effect is enhanced.

Doxorubicin can cause an increase in the concentration of uric acid in the blood, which reduces the effectiveness of antidotal drugs (including allopurinol, colchicine).

With simultaneous application with clindamycin, the risk of allergic reactions increases.

Doxorubicin can potentiate the hepatotoxic effect of mercaptopurine.

Streptozocin and methotrexate cause an increase in toxicity of doxorubicin, due to a decrease in hepatic clearance.

When applying paclitaxel simultaneously or after doxorubicin, cardiotoxicity may be increased.

Propranolol inhibits the activity of the coenzyme Q10 of the heart, so with simultaneous use, cardiotoxicity of doxorubicin may be increased.

When trastuzumab is administered simultaneously or after doxorubicin, cardiotoxicity may be increased.

With simultaneous use with cyclosporine, an increase in the concentration of doxorubicin in plasma and an increase in myelotoxic effect are observed; with cyclophosphamide, mitomycin, dactinomycin - the cardiotoxic effect of doxorubicin may be increased.

When doxorubicin is used (intravenously for 3 days) in combination with cytarabine (in the form of infusion for 7 days), cases of the development of necrotic colitis and severe infectious complications are described.

Against the background of the use of doxorubicin, inhibition of antibody formation and / or an increase in adverse reactions during the administration of live vaccines occur due to suppression of immunity. This effect can last from 3 months to 1 year.

Special instructions:

The application should be carried out by specially trained medical personnel in compliance with established precautions when preparing, diluting injection solutions (in a sterile box using disposable surgical gloves and masks) and destroying needles, syringes, vials, ampoules and the remainder of the unused preparation.

At the slightest sign of getting under the skin, the infusion should be stopped immediately and another vein should be chosen for injection.

When extravasation, immediately remove the injection needle, put the ice, give the limb an elevated position; may require surgical excision of necrotic tissue.

Do not mix in one syringe with other antitumor drugs.

During treatment, strict monitoring of blood counts (at least 2 times a week), heart and liver activity (oppression of bone marrow hematopoiesis and cardiotoxicity are dose-limiting factors) is necessary. Repeated course can be started only after complete elimination of signs of hematotoxicity.

An increase in the concentration of uric acid in the blood and the risk of developing nephropathy may require adjustment of the doses of uricosuric antidotal drugs. In the course of treatment, it is necessary to ensure sufficient fluid intake with subsequent strengthening of diuresis to ensure the excretion of uric acid.

Dental interventions should be completed as far as possible before the start of therapy or postponed until normalization of the blood picture (possibly increased risk of microbial infections, slowing healing, bleeding gums).

Do not use earlier than 1 month after previous chemotherapy.

Do not recommend the vaccination of patients and their families.

Doxorubicin can cause urine to turn red within 1-2 days after administration.

In experimental studies, the carcinogenic and mutagenic effect of doxorubicin has been established.

Instructions

Doxorubicin (Doxophyllinum)