Fitozid

General characteristics. Structure:

Active ingredient: 20 mg of an etopozid.

Excipients: macrogoal 300 (polyethyleneglycols 300), benzyl alcohol, ethanol, polysorbate 80, citric acid, sodium citrate.

Pharmacological properties:

Pharmacodynamics. Antineoplastic drug. Etopozid represents semi-synthetic derivative podophyllotoxin. The mechanism of action is connected with topoisomerase II inhibition. Etopozid has cytotoxic effect due to DNA damage. Drug blocks a mitosis, causing death of cells in a G-phase and a late S-phase of a mitotic cycle. In high concentration drug causes killing in a premitotic phase.

Etopozid also suppresses penetration of nucleotides through a plasma membrane that interferes with synthesis and recovery of DNA.

Pharmacokinetics. Later in/in introductions, Cmax in plasma makes 30 mkg/ml.

Drug is found in pleural liquid, in saliva, liver tissue, a spleen, kidneys, myometriums, brain tissues. Gets through GEB and a placental barrier. Values of concentration of an etopozid in cerebrospinal fluid vary from not defined values up to 5% of concentration in a blood plasma. Data on release of drug with breast milk are absent. Linkng with proteins of plasma makes about 97%.

Etopozid is actively metabolized in an organism. Allocation of an etopozid at the same time is carried out dvukhfazno. At adults with normal function of kidneys and a liver of T1/2 makes about 0.6-2 h from final T1/2 5.3-10.8 h.

Etopozid is brought with urine in the form of not changed substance (29%) and metabolites (about 15%) during 48-72 h 2-16% is allocated with a stake.

Indications to use:

— germinogenny tumors of a small egg;

— germinogenny tumors of ovaries;

— lung cancer.

There are messages on Fitozid's efficiency at cancer therapy of a bladder, a lymphogranulomatosis, nekhodzhkinsky lymphoma, an acute monoblast and miyeloblastny leukosis, Ewing's sarcoma, trophoblastic tumors, a carcinoma of the stomach, Kaposha's sarcoma and a neuroblastoma.

Route of administration and doses:

At the choice of a way of introduction, the mode and doses in each individual case it is necessary to be guided by data of special literature.

The mode of dosing is set individually, depending on the used scheme of chemotherapy (at the choice of a dose it is necessary to consider myelosuppressive effect of other drugs in combinations, and also action of the previous radiation therapy and chemotherapy).

Fitozid enter in/in within 30-60 min. at the same time doses usually make 50-100 mg/sq.m/days within 4-5 days, with repetition of cycles each 3-4 weeks.

The mode of introduction of Fitozid every other day on 100-125 mg/sq.m in 1, 3 and 5 days is also often applied.

Repeated courses are conducted only after normalization of indicators of peripheral blood.

Before in/in introduction Fitozid dilute in 250 ml 0.9% of solution of sodium of chloride or 5% of solution of a dextrose to final concentration of 200-400 mkg/ml. Not to allow contact with buffered aqueous solutions with рН higher than 8.

Features of use:

Use at pregnancy and feeding by a breast. Drug is contraindicated at pregnancy and in the period of a lactation (breastfeeding).

Women and men of childbearing age receiving therapy by Fitozid have to use reliable methods of contraception.

Use for children. At children under 2 years safety and efficiency of drug is not established.

Special instructions. Fitozid it is necessary to apply only under constant observation of the doctor having experience of therapy by cytotoxic drugs.

Suppression of function of marrow is dozolimitiruyushchy action of Fitozid. Regular control of cellular composition of blood needs to be carried out before an initiation of treatment, in breaks and before each subsequent course. If prior to therapy by Fitozid radiation therapy and/or chemotherapy was carried out, then it is necessary to observe a sufficient interval between these two types of treatment to provide recovery of function of marrow. In case of decrease in number of thrombocytes is lower 50 000/mkl and/or absolute number of neutrophils to 500/mkl it is necessary to stop therapy to a complete recovery of indicators of blood.

At emergence of anaphylactic reactions Fitozid's introduction it is necessary to stop and begin treatment with corticosteroids and/or antihistaminic drugs against the background of infusional therapy.

At accidental ekstravazalny introduction it is necessary to stop to enter immediately an injection and the remained portion into other vein. Introduction is stopped as soon as the burning sensation appears. Around the struck place carry out п / to an injection of a hydrocortisone and impose 1% hydrocortisone ointment (until the erythema disappears) under a dry bandage on 24 h.

With care it is necessary to use drug at patients with a liver or renal failure.

Occasionally at the patients receiving therapy etopozidy in a combination with other antineoplastic drugs the acute leukosis, both with a preleukemic phase, and without it can develop.

Due to the immunodepressive effect of drug and a possibility of development of a heavy infection, it is not recommended to apply live vaccines during chemotherapy. Vaccination should be carried out 3 months later from completion of therapy.

Before use it is necessary to use a visual estimate of solution regarding identification of solid particles or discoloration.

Fitozid's concentrate for in/in introductions as a filler contains alcohol that can be risk factor for the patients having liver diseases, alcoholism, epilepsy and also for children.

During the work with Fitozid it is necessary to follow rules of the treatment of cytotoxic drugs. In case of contact with skin or a mucous membrane affected areas need to be washed out immediately water with soap.

Side effects:

From system of a hemopoiesis: decrease in number of leukocytes and granulocytes depends on the entered dose and is the main toxic manifestation limiting Fitozid's dose. The maximum decrease in number of granulocytes is usually observed for 7-14 day after administration of drug. Thrombocytopenia arises less often, and the maximum decrease in thrombocytes is observed for 9-16 day after introduction of an etopozid. Recovery of indicators of blood happens usually for the 20th day after introduction of a standard dose. Anemia is observed infrequently.

From the alimentary system: nausea and vomiting arises approximately at 30-40% of patients. Usually these phenomena have moderate character, and it is necessary to resort to cancellation of treatment because of them seldom. For control of these side effects antiemetic drugs are shown. Besides, diarrhea, an abdominal pain, stomatitis, an esophagitis, a dysphagy, anorexia were noted. Sometimes there is a temporary hyperbilirubinemia and increase in level of transaminases. Most often it occurs at use of the doses exceeding recommended.

From cardiovascular system: at bystry in introduction at 1-2% of patients temporary decrease in the ABP which is usually recovered at the termination of injection and administration of liquids or other maintenance therapy was noted. In need of resuming of introduction of Fitozid rate of administering should be reduced.

Allergic reactions: the symptoms reminding anaphylactic such as fever, fever, tachycardia, bronchospasm, asthma and decrease in the ABP. These reactions are usually observed in time or right after introduction of an etopozid and stop at the termination of injection and use of GKS or antihistamines.

Dermatological reactions: not less than 66% - the reversible alopecia sometimes leading to full loss of hair; seldom - pigmentation, an itch, Stephens-Johnson's syndrome, a toxic epidermal necrolysis; in one case the recurrence of beam dermatitis was observed.

From TsNS and peripheral nervous system: seldom - a peripheral neuropathy, drowsiness, increased fatigue, an optic neuritis, a passing blindness of cortical genesis.

From a metabolism: seldom - a metabolic acidosis, a hyperuricemia.

Local reactions: seldom - phlebitis in an injection site. At hit of drug under skin - the expressed local irritative action up to a necrosis of surrounding fabrics.

Others: seldom - residual smack in a mouth, fever, an intersticial pneumonitis / pneumosclerosis, muscular spasms.

Interaction with other medicines:

Antineoplastic action of an etopozid amplifies at use in combination with Cisplatinum. However at the same time it is necessary to consider that at the patients who were earlier receiving treatment by Cisplatinum, removal of an etopozid can be broken.

Pharmaceutical interaction. Etopozid it is impossible to mix with other drugs in one solution.

Pharmaceutical it is incompatible with the solutions having alkaline values рН.

Contraindications:

— the expressed abnormal liver functions;

— acute infections;

— pregnancy;

— period of a lactation (breastfeeding);

— a miyelosupressiya (the quantity of neutrophils are lower 1500/mkl and/or thrombocytes lower than 75 000/mkl);

— hypersensitivity to drug components.

With care it is necessary to use drug at patients with alcoholism, epilepsy; at children's age (at children up to 2 years safety and efficiency of drug is not established).

Overdose:

Overdose cases at use of an etopozid for the person are not registered so far.

Symptoms: it is possible to assume that toxic effects from system of a hemopoiesis and a GIT will be the main manifestations of overdose.

Treatment: generally symptomatic therapy is shown. Specific antidotes do not exist.

Storage conditions:

List B. Drug should be stored in the unavailable to children, protected from light place, at a temperature up to 25 °C. Not to freeze. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

5 ml - bottles of colourless glass (1) - a pack cardboard.