Doxorubicine

General characteristics. Structure:

1 bottle contains hydrochloride doxorubicine in terms of 100% the substance which is not containing water and residual amounts of organic solvents of 0,01 g, a mannitol of 0,04 g.

Main physical and chemical properties: porous mass of red-orange color.

Pharmacological properties:

Pharmacodynamics. Doxorubicine has the expressed antineoplastic and antileukemic effect. Drug quickly gets into cells, contacts perinukleinovy chromatin, cell fission and synthesis of nucleic acids oppresses, making specific impact on a cell fission phase S, causing aberation chromosomes.

Pharmacokinetics. After intravenous administration doxorubicine is quickly distributed in plasma and  fabrics in 30 seconds drug is found in a liver, lungs, heart and kidneys. Distribution volume in an equilibrium state makes 20 30 l/kg. Within an hour after introduction doxorubicine is partially metabolized in a liver in an active metabolite. Does not get through GEB. The elimination half-life for doxorubicine and its metabolite varies from 20 to 48 hours. It is removed with bile in not changed look (about 40% within 5 days) and kidneys in not changed look and in the form of metabolites (about 5 - 12% within 5 days).

Indications to use:

Lymphoblastoid leukosis, sarcoma of soft tissues, osteosarcoma, Ewing's sarcoma, breast cancer, lung, thyroid gland, mesothelioma, malignant thymoma, cancer of a gullet, stomach, liver and bilious channels, pancreas, insuloma, hepatocellular cancer, cancer of a renal pelvis and ureters, cancer of a bladder and urethra, kidney cancer, germinogenny tumor of a small egg and ovaries, ovarian cancer, Vilms's tumor, neuroblastoma, embryonal rhabdomyosarcoma, cancer of fallopian pipes, hysterocarcinoma, uterus sarcoma, cancer of a vagina and neck of uterus, prostate cancer, multiple myeloma, lymphogranulomatosis, nekhodzhkinsky lymphoma.

Route of administration and doses:

Doksorubitsin-KMP enter only intravenously!
The dose of drug is established strictly individually by  depending on character and a phase of a disease, age, a condition of the patient and hemopoietic function.
Extra care needs to be shown at preparation and administration of drug.
The medical personnel are recommended to use gloves.
Previously contents of a bottle are dissolved at agitation in 5 ml of isotonic solution of sodium of chloride (concentration of drug makes 2 mg/ml). Dry matter and solution of red color.
It is recommended to enter solution within 3 5 minutes through a system tube for performing infusions (normal saline solution or 5% aqueous solution of glucose). Local reddening of the place around a vein or face reddening can be signs of too bystry administration of drug.
At administration of drug it is necessary to watch possibility of a perivenous ekstravazation which effect is strongly expressed local necrosis of fabric. The burning sensation in the place of use of drug can be an ekstravazation sign. In that case introduction to this vein is stopped at once and continue introduction to other vein.
The most widespread is the scheme providing intravenous administration of drug in a dose of 60 75 mg/sq.m of a body surface of 1 times every 3 week. Alternative scheme of treatment: on 20 mg/sq.m of a body surface once a week. It is considered that such route of administration is followed by more rare cardiotoxic effects.
Doksorubitsin-KMP it is possible to apply also in the dosage making 30 mg/sq.m, 3 days in a row with repetition of a course every 4 week. The total dose of Doksorubitsina-KMP should not exceed 550 mg/sq.m.
In case of an abnormal liver function the dose of Doksorubitsina-KMP is reduced depending on bilirubin level in serum, namely:

bilirubin in serum:                dose:

20,5 - 51,3 µmol/l                  of 50% of a dose

51,3 - 85,5 µmol/l                  of 25% of a dose

more than 85,5 µmol/l               use of drug are not recommended

 

The patient with the broken hemopoietic function of marrow the dose of Doksorubitsina-KMP is reduced according to quantity of leukocytes in blood, namely:

quantity of leukocytes in blood:                  dose:

3,0 - 4,0 x 10 9/l                                   75% of a dose

less than 3,0 x 10 9/l                                  use of drug are not recommended

 

The patient with an impaired renal function (glomerular filtering <10 ml/min.) is applied by 75% of a dose.
At the combined introduction of Doksorubitsina-KMP with other antineoplastic means its dose fluctuates at the level of 25 50 mg/sq.m each 4 weeks if it is entered in combination with miyelopodavlyayushchy drugs. For the patients receiving radiotheraphy on area of lungs and a mediastinum and also a combination of Doksorubitsina-KMP with Cyclophosphanum the total dose of Doksorubitsina-KMP makes no more than 400 mg/sq.m.

Features of use:

Treatment needs to be carried out at strict hematologic and cardiological control, conducting a research of a picture of blood and an ECG prior to therapy and before each subsequent course.
With care appoint the patient with heart diseases (including in the anamnesis), chicken pox (including recently postponed or after contact with the diseased), the surrounding herpes, other acute infectious diseases, gout or a nephrolithiasis (including in the anamnesis), and also to patients with the carried-out mediastinal radiation therapy or receiving at the same time cyclophosphamide.
Because of sharp disintegration of tumor cells during treatment of Doksorubitsinom-KMP there can be a secondary hyperuricemia which should be controlled and, in case of need, to treat.
Doksorubitsin-KMP widely apply in schemes of complex polychemotherapy, however it is not necessary to appoint it before 1 month after the previous chemotherapy other antineoplastic means.
Antineoplastic activity of drug is approximately identical irrespective of the scheme of introduction: whether it is entered bolyusno (the general dose) once a month, weekly doses or in the way of gradual long introduction, but schemes of introduction considerably differ on manifestation of side reactions. In particular, at long introduction, unlike bolyusny, in much smaller degree nausea and vomiting are shown.
Doksorubitsin-KMP can paint urine in red color within 1 2 days after introduction.

Side effects:

The most dangerous of side effects of Doksorubitsina-KMP limiting its dose are cardiotoxicity and a miyelosupressiya. Difficult compensated cardiotoxicity most often is shown at patients at achievement of the total dose of drug exceeding 550 mg/sq.m. At establishment of a dose for use it is necessary to consider earlier received dose of Doksorubitsina-KMP or other anthracyclines. At emergence of clinical signs of a cardiomyopathy (reduction of a voltage of the QRS complex, reduction of fraction of cordial emission) treatment by drug is recommended to be stopped.
Miyelosupressiya who is shown first of all by a leukopenia and thrombocytopenia comes, as a rule, for 10  14th day after reception of Doksorubitsina-KMP; normalization of hematologic indicators most often happens for 21 days. In case of slow recovery of level of neutrophils and thrombocytes the dose of Doksorubitsina-KMP should be lowered. Most of patients at reception of Doksorubitsina-KMP has a reversible alopecia. At children emergence of the phenomenon of a hyperpegmentation of nails and skin bends is possible.
At use of drug appetite loss, nausea and vomiting are often noted.
In single cases conjunctivitis or dacryagogue develops.
At some patients diarrhea develops.

Interaction with other medicines:

- At simultaneous use of Doksorubitsin-KMP 6 Mercaptopurinums can exponentiate a hepatotoxic action;
• at use of Doksorubitsina-KMP (in/in within 3 days) in a combination with Cytarabinum (in the form of infusion within 7 days) cases of development of necrotic colitis and heavy infectious complications are described;
• at simultaneous use of drug with cyclosporine cases of development of a coma and/or spasms are described;
• bleomycin, vinblastine, Vincristinum, Thiophosphamidum, a methotrexate, этопозид are compatible to Doksorubitsinom-KMP, Prednisolonum, 5-ftoruratsit also Cisplatinum;
• the drug cannot be administered in one syringe with heparin and 5 - ftoruratsily;
• Doksorubitsin-KMP it is incompatible with an Euphyllinum, sodium salt of cefalotin, dexamethasone and a hydrocortisone;
• simultaneous treatment at sick Doksorubitsinom-KMP with Cyclophosphanum, mitomitsiny or use it along with radiotheraphy of a mediastinum increases risk of cardiotoxic effect;
• at simultaneous use with streptozotsiny increase in an elimination half-life of Doksorubitsina-KMP is possible.

Contraindications:

The expressed leukopenia, anemia, thrombocytopenia; serious illness of cardiovascular system; acute hepatitis; pregnancy. Doxorubicine is not applied at the patients who received a full cumulative dose of a daunorubitsin, an idarubitsin and/or other anthracyclines and anthracenes.

Overdose:

The acute overdose of Doksorubitsina-KMP is shown by toxic damage of mucous membranes, a leukopenia and thrombocytopenia.
Treatment: the patient is hospitalized at once and appoint treatment antibiotics, carry out a transfusion of erythrocytes and thrombocytes, along with a symptomatic treatment of damages of a mucous membrane.
The chronic overdose of Doksorubitsina-KMP which is an effect of more prolonged use of the general dose of drug exceeding 550 mg/sq.m considerably increases risk of a cardiomyopathy and the subsequent heart failure.
Treatment: digitalis drugs, diuretics and peripheral vasodilators.

Storage conditions:

To store in the dry, protected from light place, at a temperature not above + 5 °C. Period of validity 2 years. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

In bottles on 0,01 g.