Rastotsin

General characteristics. Structure:

Acting a vechestvo: 10 mg of doxorubicine of a hydrochloride in the form of the lyophilized substance.

Pharmacological properties:

Растоцин® treats group of anthracycline antibiotics with antineoplastic action. It is allocated from culture of Streptomycces peucetius var. caesius.
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. The clearance of doxorubicine in serum is high, binding in fabrics extensive. Within an hour after introduction doxorubicine is partially metabolized in a liver in an active metabolite адриамицинол. Further decomposition of drug continues also in a liver. Drug does not get through a blood-brain barrier. Time of semi-removal from plasma (T1/2 an alpha) makes 0,6 h within a week after introduction about 40-50% of the received dose of doxorubicine is allocated with bile (50% in the form of doxorubicine, 23% in the form of an adriamitsinol). Within 5 days about 4-5% of a dose it is allocated with urine.

Indications to use:

- acute lymphoblastic leukosis;
- acute miyeloblastichesky leukosis;
- malignant lymphoma;
- Vilms's tumor;
- neuroblastoma;
- sarcoma of soft tissues;
- osteosarcoma;
- breast cancer, ovaries, bladder, thyroid gland, lungs and stomach.

Route of administration and doses:

Растоцин® it is applied one (monotherapy) or in a combination with other antineoplastic drugs (polychemotherapy).

The dose of Rastotsina® usually makes 60-75 mg/m ² body surfaces once intravenously with repetition of a course every 3 week. The alternative scheme of treatment on 20 mg/m ² body surfaces once a week. It is considered that such route of administration is followed by more rare cardiotoxic effects.

Растоцин® it is possible to apply also in the dosage making 30 mg/m ² / days 3 days in a row with repetition of a course every 4 week. The total dose of doxorubicine should not exceed 550 mg/m ² body surfaces.

In case of an abnormal liver function the dose of doxorubicine is reduced depending on bilirubin level in serum, namely:

bilirubin in serum       a 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 contraindicated

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

quantity of leukocytes in blood        a dose 
3-4                                         109/L 75% of a dose
less than 3 109/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.

Solution preparation

Contents of a bottle are dissolved at agitation in 5 ml of isotonic solution or twice distilled water, and concentration of doxorubicine makes 2 mg/ml. Dry matter and solution of red color.

Way of administration of drug

Растоцин® enter intravenously. It is recommended to enter solution within 3-5 minutes through a system tube for infusion introduction (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 monitor prevention of a perivenous ekstravazation, an effect of what 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.

Precautionary measures during the work with drug

Extra care needs to be shown at preparation and administration of solution of doxorubicine. The medical personnel are recommended to use gloves. In case of hit in eyes of solution or powder on skin or a mucous membrane immediately it is necessary to wash this place a stream of water and after that soap.

Features of use:

At treatment by doxorubicine of the patients having urate diathesis it is necessary to raise a dose of urikozurik.

Simultaneous treatment of patients with doxorubicine and cyclophosphamide, mitomitsiny or along with mediastinum radiotheraphy, increases risk of toxic effect by heart therefore such patient needs especially careful control. The maximum total dose at such patients makes no more than 400 mg/m ². Simultaneous use of Rastotsina® with drugs with hepatotoxic effect (e.g. high doses of a methotrexate) can break function of a liver and increase toxicity of doxorubicine. Use of the drugs suppressing function of marrow or radiotheraphy can increase myelosuppressive effect of at the same time applied doxorubicine in this connection reduce doses of drugs.

Simultaneous administration of doxorubicine and other drugs is not recommended.

Side effects:

One of the most important undesirable side effects which limit a dose is dysfunction of a myocardium and a miyelosupressiya.

Unusual, however, serious undesirable by-effect at use of doxorubicine is also dysfunction of the left heart valve and/or a cardiomyopathy. This toxic effect is more often shown at the patients receiving drug in the dose exceeding 550 mg/m ². At establishment of the general applied dose it is necessary to consider earlier received dose of other anthracyclines. The cardiotoxic effect of drug needs to be established perhaps earlier, however heavy dysfunctions of heart can be shown despite the preliminary normal ECG. Continuous reduction of a voltage of the QRS complex or reduction of fraction of emission of heart (ultrasonography or radio isotope angiocardiography) draw the attention of the doctor to a possibility of manifestation of a cardiomyopathy owing to what it is recommended to stop treatment.

Treatment by doxorubicine often causes suppression of function of marrow, especially white blood. The leukopenia usually comes for the 10-14th day after doxorubicine reception, however, the number of leukocytes is normalized for the 21st day. The number of leukocytes can decrease on less than 109/l. it is necessary to mention, as the number of erythrocytes and thrombocytes can also decrease. In case of slower recovery of blood cells a dose of doxorubicine it is necessary to lower or stop use before recovery of a picture of blood. At most of patients at use of doxorubicine the general (passing) alopecia develops. At children the phenomenon of a hyperpegmentation of nails and skin bends is possible.

At use of drug appetite loss, nausea and vomiting is often noted. Sometimes it is necessary to apply also antiemetics. During the first 10 days of treatment the inflammation of a mucous membrane of an oral cavity and/or a gullet is possible. An effect of such inflammation sometimes are the ulcers representing sources of heavy infections. The ulcer and a necrosis of a mucous large intestine can be the cause of bleeding and/or fecal infection. At some patients diarrhea develops.

At use of drug the phlebosclerosis, especially is sometimes noted if the drug is administered in a small vein. Face reddening and reddening around a vein are signs of too bystry administration of drug. In case of an ekstravazation there can come the silnovyrazhenny necrosis of fabric with or without burning sensation. Very seldom as side effect conjunctivitis or lacrimation develops.

Also hypersensitivity on drug which can be shown also in the form of anaphylactic reaction is noted.

Contraindications:

• hypersensitivity to doxorubicine;
• considerable disturbance of the hemopoietic function of marrow, owing to the previous chemotherapy or radiation therapy;
• heavy abnormal liver functions (bilirubin> of 85,5 µmol/l);
• patients, earlier treated maximum total doses of anthracyclines.

Use of drug is not recommended to patients with the heart diseases which are available in the anamnesis.

Preventions

It is recommended to carry out control of a picture of blood and an ECG before an initiation of treatment and before each subsequent cycle of treatment.

Drug is used only under strict control of the doctor with experience in use of chemotherapeutic means.

In an initiation of treatment doxorubicine of the patient recommends to hospitalize.

Because of sharp disintegration of tumor cells during treatment by doxorubicine there can be a secondary hyperuricemia which should be controlled and to treat in case of need.

It is necessary to warn the patient that during the first 1-2 days of treatment by doxorubicine perhaps passing reddening of urine.

At patients with the broken function of a liver it is necessary to conduct a research of function of a liver (bilirubin, transaminases, an alkaline phosphatase) and according to these data to define a drug dose.

Special attention should be paid on patients with disturbance of cordial functions.

With care, along with reduction of a dose of drug, it is necessary to treat doxorubicine of patients with the broken function of marrow (miyelosupressiya).

Lower doses of drug are applied by the patient of senile age (more than 70 years).

Pregnancy and period of a lactation

Use of doxorubicine is not recommended to pregnant women and the nursing mothers. As antineoplastic drugs have teratogenic and mutagen effects, at use of doxorubicine it is necessary to estimate possible advantage and risk concerning a fruit.

Overdose:

The acute overdose of doxorubicine is shown by an inflammation of a mucous membrane of an oral cavity and a gullet, a leukopenia and a thrombopenia. The patient in that case is hospitalized at once and appoint treatment antibiotics, carry out a transfusion of erythrocytes and thrombocytes, along with a symptomatic treatment of an inflammation mucous.

The chronic overdose of doxorubicine which is an effect of more prolonged use of the general dose of drug exceeding 550 mg/m ² substantially increases risk of a cardiomyopathy and the subsequent heart failure that results in need of use of drugs of a digitalis, diuretics and peripheral vasodilators.

Storage conditions:

Period of validity 24 months.

Issue conditions:

According to the recipe

Packaging:

10 bottles. Растоцин® it is applied only in stationary conditions.