Dacarbazine

Dakarbazine is one of the most popular antitumor drugs that causes the death of malignant cells by rupturing the integrity of DNA chains. The use of this drug in oncology is so common that it allows us to draw positive conclusions about its effectiveness.

[1], [2],

Indications Dacarbazine

Indications for the appointment of Dakarbazin are malignant diseases of tissues and organs:

• treatment of melanoma, lymphogranulomatosis, sarcoma (except for multiple hemorrhagic sarcomatosis);
• complex systemic therapy of osteogenic sarcoma, lymphosarcoma, uterine sarcoma, embryonic rhabdomyosarcoma, peritoneal and pleural mesothelioma;
• treatment of epithelial carcinomas (bronchogenic tumors, multicellular lung cancer, thyroid cancer), neuroblastomas, gliomas, pheochromocytomas.

[3], [4], [5]

Release form

White powdery substance, used as a solution for intravenous injection. Produced in doses of 100 or 200 mg, in hermetically sealed bottles.

[6], [7], [8], [9]

Pharmacodynamics

Under the influence of the drug, the synthesis of DNA is disrupted, due to the formation of complex compounds with carbocation and the inhibition of mitotic cellular activity.

In the process, the release of diazomethane, which is capable of forming covalent bonds with functional molecular groups, occurs. Perhaps its antimetabolic action.

Dakarbazine begins to show the highest degree of activity after the process of formation of hepatic metabolites. The drug does not have phase specificity.

[10], [11], [12]

Pharmacokinetics

Immediately after absorption, the drug is quickly distributed, without remaining in the blood serum. In small amounts, binding to proteins occurs.

It has poor solubility in lipid compounds. Relatively in a small concentration passes through the blood-brain barrier.

Metabolism is found in the liver, partially excreted by the kidneys. Partial excretion is about 20 minutes, with disorders of the urinary system this period is prolonged.

Almost half of the administered dose of the kidney is removed within six hours.

[13], [14], [15], [16]

Dosing and administration

The drug is used for intravenous and sometimes for intra-arterial administration. Dosage is established strictly individually, if necessary combining with other chemotherapeutic agents, taking into account the degree of possible intoxication and the dynamics of the disease.

The therapeutic solution is prepared in combination with water for injection in a ratio of 10 mg of the drug per 1 ml of water. The dropwise method of administration involves the addition of a 5% dextrose solution or an isotonic sodium chloride solution to 250 ml.

Prepared infusion solutions can be stored for up to three days in a refrigerator or up to 8 hours at a temperature of up to 24 ° C.

The cycle of therapy lasts about a week with a further break in 21 days. The duration of cycles and their number is determined by the doctor individually.

[20], [21], [22], [23]

Use Dacarbazine during pregnancy

This drug has strict contraindications for admission to the period of gestation and breastfeeding. Recent scientific studies have confirmed the teratogenic effects of Dacarbazine on the embryo.

When treating women of reproductive age, the latter is recommended to abstain from sexual intercourse for the period of therapy, or to use reliable contraceptives.

Lactation at the time of taking the drug should be discontinued.

Contraindications

Contraindications for taking Dakarbazin are:

• allergic sensitivity to any of the constituents of the drug;
• impaired bone marrow function;
• severe disorders of the liver and organs of the urinary system;
• the period of gestation and feeding of the child;
• oppression of the central nervous system;
• viral, fungal and bacterial infections (due to the possibility of uncontrolled proliferation of the process);
• application of radiation therapy.

[17], [18]

Side effects Dacarbazine

Side effects during treatment with the drug are quite common and can be the following symptoms:

• bleeding gums, hemorrhagic digestive system, dyspeptic disorders, pain in the liver and stomach, thrombotic lesions of the veins of the liver;
• anemia, thrombophlebitis, hemorrhages in the organs and mucous membranes;
• disorders of outflow of urine, menstrual cycle disorders, spermatogenesis;
• violations of skin sensitivity, redness of the skin, the appearance of swelling;
• in the zone of drug administration, trophism of tissues, scarring;
• hyperthermia, decreased immunity, disseminated pain, anaphylaxis.

[19]

Overdose

The following signs of drug overdose are possible:

• dyspeptic disorders;
• damage to the bone marrow and a decrease in its hematopoietic activity;
• febrile conditions;
• diffuse hemorrhage.

With symptoms of an overdose of Dakarbazine, there is no specific treatment. The measures of symptomatic therapy, strict control of the functionality of all organs and systems, the appointment of blood transfusion, the use of certain types of antibiotics.

[24], [25], [26]

Interactions with other drugs

Dakarbazine, when ingested, has a certain toxic effect on it: this effect can be enhanced by the simultaneous administration of some hypnotics, as well as rifampicin, phenytoin.

The drug can enhance the effects on the body of allopurinol, azathioprine, mercaptopurine.

A photosensitizing effect is possible in combination with methoxypsoralen.

There is a chemical incompatibility of Dacarbazine with heparin preparations, hydrocortisone, sodium hydrogen carbonate.

[27], [28],

Storage conditions

The drug should be stored in a medical institution or pharmacy in a safe or a closet, in a cool and dark place. It requires special care during storage and use, so all manipulations with the drug are carried out by special personnel who are aware of the issues of chemotherapy, using certain methods of protection.

[29], [30], [31]

Special instructions

The drug Dakarbazin belongs to list A, therefore its purpose, solution preparation and administration is performed only by a medical specialist. Pharmacies do not engage in the free sale of this medication.

[32], [33], [34], [35], [36], [37]

Shelf life

Shelf life of the drug is 2 years.

[38], [39]