Dakarbazin

General characteristics. Structure:

Active substance: dakarbazin 100 mg or 200 mg respectively.

Auxiliary substances: lemon acid, Mannitolum.

Pharmacological properties:

Pharmacodynamics. Dakarbazin is an antineoplastic means of the alkylating action on chemical structure representing itself 5 (3,3-dimethyl-1-triazeno) - imidazole-4-karboksamid.

Drug becomes active after metabolism in a liver. Assume that there are three ways of the mechanism of action dakarbazina: alkylation for the account of ions karboniya, oppression of the purine bases and interaction with SH groups. Drug fazonespetsifichen.

Pharmacokinetics. The peak of concentration in plasma is usually reached at once directly after intravenous administration of drug. Linkng with proteins very low (about 5%). Dakarbazin gets through a hematoencephalic barrier in very small quantities. There are no data on penetration it through a placenta and hit in breast milk. Drug is removed from an organism in the two-phase way with an initial half-cycle about 20 minutes and final - about 5 hours, at disturbance of functions of a liver or kidneys these indicators make about 55 minutes and 7 hours respectively.

Drug is exposed dimetilirovaniyu pochenochny microsomal enzymes with formation of CO2 which is removed with the exhaled air and aminoimidazolkarboksamida, removed with urine. 40% of drug are removed by kidneys in an invariable look generally for the account of glomerular filtering.

Indications to use:

- melanoma,
- lymphogranulomatosis,
- sarcomas of soft fabrics.

In specialized literature there are messages on efficiency of use dakarbazina in a combination to other tsitostatikami at treatment of osteogene sarcomas, sarcomas Kaposhi, sarcomas of a uterus, testicular tumors, tumors of a GIT and a neuroblastoma.

Route of administration and doses:

The drug is administered strictly intravenously struyno within 1-2 minutes.

In quality monoterapii dakarbazin apply in a dose 200-250 mg/sq.m daily within 5 days. Repeated courses are conducted with an interval of Z weeks. At a combination to other tsitostatikami dakarbazin it is entered in a dose of 100-150 mg/sq.m of 4-5 days in a row, at the same time treat with an interval of 4 weeks.

Before introduction drug part with water for injections before achievement of concentration of 10 mg / 1 ml.

Side effects:

From system of blood formation: Oppression of a myelopoiesis yavyaltsya by the by-effect limiting a dose and can carry the expressed character. Leykotsitopeniya is usually observed for the 14th day, thrombocytopenia - for the 18th day after the end of therapy and lasts on average up to 1 week. Cases of early signs of oppression of a hemopoiesis (10-12 days) of an also late were reported (for the 30th day of treatment). Recovery of indicators of blood happens by 4th week. Anemia was sometimes observed.

From a gastrointestinal path: The most frequent complications are the expressed nausea and vomiting which usually arise during the first 2 days of treatment and are well stopped by antiemetic drugs. At some patients during this period the diarrhea is observed. In single cases stomatitises are noted.

Local reactions: Pain in the place of an injection and on the vein course. At hit of drug under skin - the expressed morbidity, a necrosis of surrounding fabrics.

Others: In 3-5% of cases a grippopodobny syndrome (increase in temperature to 39 °C, expressed mialgiya and the general indisposition), reversible increase in level of liver enzymes in blood serum, head pain, paresthesias are observed. At certain patients skin rash, an alopecia, phlebitis, reddening of the person are observed.

Prevention and precautionary measures: The drug has to be administered under observation of the doctor having sufficient experience in antineoplastic therapy. Special attention should be paid to systematic control of blood indicators.

Interaction with other medicines:

The drugs inducing microsomal enzymes of a liver (barbiturates, rimfampitsin, Phenytoinum) at simultaneous use can exponentiate toxic action dakarbazina. Use dakarbazina in a combination to Mercaptopurinum, Azathioprinum and Allopyrinolum can exponentiate action of the last and increase their toxicity.

Contraindications:

• the increased sensitivity to drug,
• pregnancy and period of feeding by a breast.

Overdose:

At overdose it is necessary to expect strengthening of oppression of a marrowy hemopoiesis and gastrointestinal toxicity. The specific antidote is not known. Symptomatic treatment.

Storage conditions:

To store in the place, unavailable to children, at a temperature not above 25 °C, to protect from light. Period of validity 2 years. Divorced drug can be stored in the dark place no more than 6 hours. Drug should not be used after the term of the validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

The bottles containing 100 mg or 200 mg dakarbazina. On 10 bottles or to 1 bottle in packaging.