Doxorubicin

When ATH:
L01DB01

Characteristic.

Antibiotic anthracyclines, isolated from a culture Streptomyces peuceticus var. more deadly. Molecular weight 579,99. Red crystalline powder or porous weight. Sparingly soluble in water, insoluble in alcohol. Unstable in solutions with a pH of less than 3 and more 7.

Pharmacological action.
Antitumor.

Application.

Acute leukemia lymfoblastnыy and myeloblastnыy; malignant lymphoma Hodgkin's and non-Hodgkin type; mammary cancer, light (especially small cell), Bladder, Thyroid, ovary; osteosarcoma; soft tissue sarcoma; sarkoma Juinga; sympathicoblastoma; Wilms' tumor.

Contraindications.

Hypersensitivity to hydroxybenzoates, pronounced suppression of bone marrow function due to administration of other chemotherapeutic drugs or radiation therapy, previous treatment with anthracyclines in the limiting cumulative doses, leukopenia, thrombocytopenia, anemia, severe liver and kidney, acute hepatitis, bilirubinemia, severe heart disease (miokardit, expressed arrhythmias, acute phase of myocardial infarction), gastric ulcer and duodenal ulcer, bleeding, tuberculosis, cystitis (intravesical), pregnancy, lactation.

Restrictions apply.

Age to 2 and after 70 years (may increase the frequency of cardiotoxicity), organic heart disease (the risk of cardiac toxicity at low doses).

Pregnancy and breast-feeding.

Contraindicated in pregnancy.

Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)

At the time of treatment should stop breastfeeding.

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): ≤10% (with a total dose of more than the total 550 mg / m²) - Congestive heart failure, manifested by shortness of breath, swelling of feet and ankles, fast or irregular heartbeat, and demands the immediate cessation of treatment, tk. It may develop irreversible and ultimately fatal cardiomyopathy (depending on the dose and duration of treatment, she may develop several weeks after discontinuation of the drug); Acute atrial and ventricular arrhythmias (preferably during the first hours after administration); rarely, within a few days or weeks after administration - toxic myocarditis or a syndrome, myocarditis, pericarditis (tachycardia, heart failure, perikardit); thrombocytopenia, leukopenia, peaks 10-15 days after the start of treatment (blood picture returns to normal on 21 day after discontinuation of); fleboskleroz (when administered in small veins or repeated administration in the same vein), flushing and redness along the vein (at too rapid introduction).

From the digestive tract: nausea, vomiting, stomatitis or esophagitis (may occur 5-10 days, particularly when administered over 3 consecutive days, and lead to serious infection), ulceration in the gastrointestinal tract; rarely - anorexia, diarrhea.

With the genitourinary system: hyperuricemia, nephropathy (It is associated with increased production of uric acid), reddish coloration of urine (disappears within 48 no). When intravesical - burning in the bladder and urethra, dysuria (soreness, difficulty, etc.), hematuria.

For the skin: alopecia (complete and reversible), darkening the soles, hands and nails, recurrence of radiation erythema.

Allergic reactions: skin rash, itch, fever, chills, anaphylaxis.

Other: extravasates, cellulitis, necrosis (when released into the surrounding tissue), rarely - conjunctivitis, lacrimation.

Cooperation.

Pharmaceutical incompatible with heparin solution, deksametazona, ftoruracila, hydrocortisone sodium succinate, aminofillina, cephalothin (possible precipitation). Streptozocin increases T_1/2 doxorubicin. It enhances the toxic effects of other anti-tumor agents (aggravation of hemorrhagic cystitis, cyclophosphamide-induced, increase hepatotoxicity of 6-mercaptopurine and others.) and radiation therapy (on bone marrow function, myocardial, mucosa, skin and liver). It reduces the effect of inactivated and live virus vaccines. May exacerbate the side effects of live virus vaccines.

Overdose.

Symptoms: increased toxic effects (mucositis, leukopenia, thrombocytopenia).

Treatment: antibiotic therapy, granulocyte transfusions weight, symptomatic treatment of mucositis.

Dosing and Administration.

B / slowly (for at least 2-5 min), isotonic sodium chloride solution or water for injection (concentration 2 mg / ml), 60-75 Mg / m² 1 every 3-4 weeks, or 20-30 mg / m² during 3 days every 3-4 weeks, or 30 mg / m² body surface 1 once every 1, 8 and 15 days course. The break between courses - 3-4 weeks. Intravesical - 30-50 mg 1 once a week at intervals of 1 Sun to 1 Months. In the combination therapy - 25-50 mg / m² every 3-4 weeks. Heading 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 reduce the dose to 50 and 75% respectively. When the level of bilirubin 12-30 mg / ml or higher 30 mg / l dose is reduced by 50 and 75% respectively.

Precautions.

During treatment requires strict control of blood parameters (at least 2 once a week), activity of the heart and liver (suppression of bone marrow hematopoiesis and cardiotoxicity are dose-limiting factors). Repeated course can begin only after the complete elimination of symptoms gematotoksichnosti.

To use caution in patients with poor bone marrow reserve, due to age, prior use of cytotoxic agents or radiation therapy.

Dental procedures should be completed before the start of therapy or deferred until the normalization of the blood picture (may increase the risk of microbial infection, slowing the healing process, krovotochivosty right).

At the slightest sign of getting under the skin of the infusion should be discontinued immediately and choose another vein injection.

Do not apply earlier than 1 Months after prior chemotherapy.

Increasing the concentration of uric acid in the blood and the risk of developing nephropathy may require adjustment of doses urikozuricheskih protivopodagricakih funds. In the course of treatment is necessary to ensure sufficient fluid intake, followed by increased urine output for excretion of uric acid.

Cautions.

Application must be done by specially trained medical personnel with the established precautions when cooking, dilution of injectable solutions (in a sterile box with the use of disposable surgical gloves and masks) and disposal of needles, syringes, bottles, ampoules and the remainder of the unused product.

Do not mix in the same syringe with other anticancer drugs.

Cooperation