Doxorubicine

Doxorubicine – an anthracycline antineoplastic antibiotic with anti-proliferative and antimitotic action.

Form of release and structure

Dosage forms:

• Lyophilisate for preparation of solution for intravascular and intravesical introduction (on 10 ml in bottles, in a cardboard box of 10 pieces);
• Concentrate for preparation of solution for intravascular and intravesical introduction (on 5 ml in glass bottles, in a cardboard pack of 1 or 10 pieces; on 25 or 50 ml in glass bottles, in a cardboard pack of 1 piece).

Active agent – doxorubicine a hydrochloride:

• 1 bottle of lyophilisate – 10 mg;
• 1 ml of a concentrate – 2 mg.

Auxiliary component of lyophilisate – Mannitolum.

Indications to use

Use of Doxorubicine is shown at treatment of the following oncological diseases: an osteosarcoma, sarcoma of soft tissues, Ewing's sarcoma, Kaposha's sarcoma (patients have AIDS), a malignant thymoma, a retinoblastoma, a hepatoblastoma, a neuroblastoma, Vilms's tumor, trophoblastic tumors, carcinoid, an acute miyeloblastny leukosis, an acute lymphoblastoid leukosis, a chronic lymphoid leukosis, a nekhodzhkinsky lymphoma, a multiple myeloma, a lymphogranulomatosis, small-celled cancer of a lung, a breast cancer, cancer of a thyroid gland, gullet cancer, primary hepatocellular cancer, a carcinoma of the stomach, a pancreatic cancer, ovarian cancer, a germinogenny tumor of a small egg, endometrial cancer, a prostate cancer, cancer of a neck of uterus, cancer of adrenal glands, bladder cancer (including prevention of a recurrence after surgery).

Contraindications

• The expressed functional oppression of marrow against the background of use of radiation therapy and other chemotherapeutic means;
• Leukopenia;
• Acute hepatitis;
• Heavy abnormal liver functions;
• Thrombocytopenia;
• Serious illness of heart, including the expressed disturbances of a rhythm, myocarditis, an acute phase of a myocardial infarction;
• Anemia;
• The previous therapy in limit total doses anthracyclines;
• Period of pregnancy and breastfeeding;
• Hypersensitivity to hydroxybenzoates.

Besides, intravesical administration of drug is contraindicated to patients with invasive tumors with a penetration in a bladder wall, with infections and an inflammation of urinary tract and a bladder.

Route of administration and dosage

Lyophilisate is intended for intravesical, intravenous (in/in) or intra arterial (in / and) introductions.

Use of drug is shown both at monotherapy, and at a combination with other cytostatic means in the doses corresponding to the scheme of treatment.

The dose is appointed by the oncologist individually.

Lyophilisate of doxorubicine of a hydrochloride is recovered by water for injections or 0,9% chloride sodium solution just before use. A necessary single dose of the received solution in addition part in 0,9% chloride sodium solution in a proportion no more than 1 mg of drug on 1 ml.

At in appointment the received solution is entered into the port for system injections for in/in injections within 3-10 minutes during bystry infusion of 0,9% of solution of sodium of chloride or 5% of solution of a dextrose. Before introduction it is necessary to make sure that the needle (or a catheter) is established precisely in a vein. Administration of drug in veins over joints or in small veins is undesirable, it is impossible to enter into extremities with the lymphatic and venous outflow broken by a venipuncture.

The recommended dosing at in introduction:

• Monotherapy: on 1 cycle of therapy on 60-75 mg on 1 sq.m. of a body surface each three weeks, usually, cyclic dose is entered once, in need of it it is possible to divide into several doses, for example, on 25-30 mg on 1 sq.m. a day in the first 3 days of a cycle. For decrease in toxic action, especially cardiotoxicities of doxorubicine, administration of drug can be made weekly on 10-20 mg on 1 sq.m.;
• The combined treatment: doxorubicine a hydrochloride each 3-4 weeks appoint in a cyclic dose 30-60 mg to 1 sq.m. Each following administration of drug is possible only in the absence of toxicity signs, in particular hematologic and gastrointestinal.

The total dose of Doxorubicine should not exceed 550 mg on 1 sq.m.

The patients who was earlier applying other cardiotoxic means or receiving radiation therapy on pericardiac or area of a mediastinum, introduction of a total dose of doxorubicine need to carry out more than 450 mg on 1 sq.m. under strict monitoring of function of heart.

At patients with an abnormal liver function the dose of drug should be lowered according to the level of concentration of the general bilirubin in blood serum: at the level of bilirubin of 1,2-3 mg/dl, decrease is made for 50% of the recommended dose if exceeds 3 mg/dl – for 75%.

It is recommended to make increase in intervals between cycles or purpose of lower doses to the patients who earlier received extensive antineoplastic therapy, the patient with the obesity, tumoral infiltration of marrow sick of advanced and children's age.

Administration of Doxorubicine in a bladder is appointed at treatment of superficial tumors of a bladder and prevention of a recurrence after a transurethral resection. Intravesical introduction is not suitable for treatment of invasive tumors with a penetration in a muscular wall of a bladder.

The recommended dosing for intravesical introduction – on 30-50 mg on one installation, depending on the use purpose – treatment or prevention, a break between procedures can make from 1 week to 1 month. To provide uniform impact on all mucous surface of a bladder, after installation, the patient has to change every fifteen minutes position of a body from one side for another. Drug has to be in a bladder within 1-2 hours, then the patient has to empty it.

At emergence of symptoms of chemical cystitis (discomfort in a bladder, a dysuria, a nocturia, a polyuria, a hamaturia, an urodynia, a bladder wall necrosis) a dose it is necessary to dissolve 0,9% of solution of sodium of chloride in 50-100 ml. Special attention is recommended to be paid to catheterization problems, including at treatment of patients with the obstruction of an urethra caused by massive intravesical tumors.

Intra arterial introduction to the general hepatic artery is appointed to patients with hepatocellular cancer for the purpose of ensuring the strengthened local influence and simultaneous decrease in the general toxic load of an organism. Dosing makes on 30-150 mg on 1 sq.m. with a break from 3 weeks to 3 months. Use of higher doses is allowed only at a possibility of simultaneous extracorporal removal of drug.

Doxorubicine in the form of a concentrate is intended for in/in and intravesical introduction. The mode of dosing depends on a condition of the patient, clinical indications and the scheme of cytotoxic therapy.

Side effects

Use of Doxorubicine can cause side effects:

• From bodies of the digestive tract (DT): vomiting, nausea, an esophagitis or stomatitis (can appear in 5-10 days, most possibly after 3 consecutive days of introduction, and to cause development of heavy infections), an ulceration in a GIT; seldom – diarrhea, anorexia;
• From cardiovascular system and system of a hemopoiesis: less than at 10% of the patients who received the general total dose more than 550 mg on 1 sq.m. of a body – congestive heart failure, with manifestations in the form of an asthma, the speeded-up or spasmodic heartbeat, puffiness of anklebones and feet (pathology demands immediate drug withdrawal as there can be a development of an irreversible, lethal cardiomyopathy, the probability of its development after drug withdrawal depends on the received dose and the period of treatment); acute ventricular and atrial arrhythmia (as a rule, during the first hours after introduction); seldom (after use during from several days to several weeks) – toxic myocarditis or a syndrome of a pericardis myocarditis (heart failure, a pericardis, tachycardia); the leukopenia reaching peak by 10-15 day of treatment (the blood count is usually recovered for 21 days after completion of use of drug); thrombocytopenia; in case of very bystry introduction – a hyperemia on the course of a vein and rush of blood to the person; a phlebosclerosis (at introduction to small veins or several times in a row in one vein);
• From urinogenital system: a nephropathy, a hyperuricemia, urine discoloration (urine gets the reddish coloring disappearing within 48 hours); at intravesical introduction – burning in an urethra and a bladder, a zatrudnennost, morbidity and other frustration of an urination, a hamaturia, cystitis;
• Allergic reactions: an itch, skin rash, a fever, the increased body temperature, an anaphylaxis;
• From integuments: darkening of nails, palms and soles; development of a full and reversible alopecia; recurrence of a beam erythema;
• Others: cellulitis, extravasate, a necrosis (in case of hit in surrounding fabrics), it is rare – dacryagogue, conjunctivitis.

Special instructions

Doxorubicine cannot be mixed with other antineoplastic means in one syringe.

During treatment it is necessary regularly (at least 2 weekly) to control blood indicators, action of the heart and a liver as dozolimitiruyushchy factors are cardiotoxicity and oppression of a marrowy hemopoiesis. A course of repeated therapy can be conducted only at total absence of signs of a gematotoksichnost.

Patients with the previous cytotoxic or radiation therapy, the patient of advanced or children's age with an insufficient reserve of marrow should appoint drug with care.

Any dental interventions should be carried out prior to Doxorubicine use as their carrying out during treatment can increase risk of microbic infections, bleeding of gums and to promote delay of processes of healing.

Injection should be stopped immediately at hit of drug under skin and to continue an injection in other vein.

After chemotherapy drug should be used not earlier than in 1 month.

At increase in risk of development of a nephropathy against the background of growth of level of concentration of uric acid in blood serum it is necessary to carry out correction of doses of uricosuric antigouty drugs. In the course of therapy it is necessary to provide consumption of enough liquid and strengthening of a diuresis for removal of uric acid.

The procedure of use of drug has to be made with observance of the standard measures of sterility at preparation and dilution of injection solutions by specially trained medical personnel. After holding a procedure, the used syringes, needles, bottles, ampoules and the remains of unused drug are subject to utilization.

Medicinal interaction

Active ingredient of Doxorubicine has high activity therefore only the oncologist can consider his interaction with at the same time accepted drugs.

Terms and storage conditions

To protect from children.

To store in the place protected from light at a temperature: lyophilisate – is not above 5 °C, a concentrate – 2-8 °C, not to freeze.

Period of validity – 2 years.