Dakarbazine - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Alkylating agents

Included in the formulation

Dakarbazin Lahema

lyophilizate in / in

Pliva-Lahema, AO Czech Republic

Dakarbazin medak

lyophilizate in / in

medac GmbH Germany

Dakarbazin-Lens®

lyophilizate in / in

VEROPHARM SA Russia

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

ONLS

VED

АТХ:

L.01.A.X Other alkylating preparations

L.01.A.X.04 Dacarbazine

Pharmacodynamics:

The mechanism of action is the formation of an active metabolite - diazomethane covalently binding to SH groups of biomolecules and blocking the synthesis of RNA and DNA by formation of carbonium ions, which leads to a stop of mitosis and inhibits the growth of tumor cells. Being an analogue of the purine base, it has the properties of antimetabolite.

Pharmacokinetics:

The connection with plasma proteins is insignificant (5%), penetration through the blood-brain barrier is also insignificant. Metabolised by the liver to 5-aminoimidazole-4-carboxamide. The half-life period consists of two phases, the alpha phase is 19 minutes, the beta phase is 5 hours, if the patient has a renal dysfunction, then the alpha and beta phases are 55 minutes and 7.2 hours, respectively. Excreted by the kidneys (40%), with half output unchanged.

Indications:

Soft tissue sarcoma (other than Kaposi's sarcoma), lymphogranulomatosis, malignant melanoma, neuroblastoma,malignant neoplasms of the gastrointestinal tract, testicular tumors, as part of multicomponent chemotherapy.

ICD-10

II.C15-C26.C25.4 Malignant neoplasm of islet cells of the pancreas

II.C15-C26.C26 Malignant neoplasm of other and inaccurately indicated digestive organs

II.C30-C39.C34 Malignant neoplasm of bronchi and lungs

II.C40-C41.C40.9 Malignant neoplasm of bones and articular cartilage of limb, unspecified

II.C43-C44 Melanoma and other malignant neoplasms of the skin

II.C45-C49.C45.0 Mesothelioma of the pleura

II.C45-C49.C45.1 Mesothelioma of peritoneum

II.C45-C49.C49 Malignant neoplasm of other types of connective and soft tissue

II.C51-C58.C54 Malignant neoplasm of uterine body

II.C60-C63.C62 Malignant neoplasm of testis

II.C69-C72.C70.0 Malignant neoplasm of cerebral membranes

II.C69-C72.C71 Malignant neoplasm of brain

II.C73-C75.C73 Malignant neoplasm of thyroid gland

II.C73-C75.C74.1 Malignant neoplasm of adrenal medulla

II.C81-C96.C81 Hodgkin's disease [lymphogranulomatosis]

II.C81-C96.C85.0 Lymphosarcoma

Contraindications:

- Hypersensitivity;

- Chronic kidney / liver diseases;

- Severe oppression of hematopoiesis;

- Pregnancy;

- Lactation period.

Carefully:

Patients who had previously received radiation therapy or took cytotoxic drugs. Acute infectious diseases viral (including chicken pox, shingles), fungal or bacterial nature (risk of severe complications and generalization of the process).

Pregnancy and lactation:

Category FDA - C. Dakarbazin is contraindicated in pregnancy. If it is necessary to use lactation, breastfeeding should be discontinued.

Women of childbearing age should use reliable methods of contraception.

In experimental studies, toxic effects of dacarbazine on the fetus have been identified.

Dosing and Administration:

Introduction intravenous. The dose is selected individually by the attending physician. The usual dose for an adult is 200-250 mg / m² surface of the body 1 time per day for 5 days, then the course is repeated after 3 weeks. If the drug is used in combination with other cytostatics - 100-150 mg / m² for 4-5 days, then repeat course in 4 weeks, or 375 mg / m² for 15 days.

Side effects:

From the digestive tract: stomatitis, diarrhea, vomiting, anorexia, bleeding in the gastrointestinal tract, liver damage.

From the genitourinary system: amenorrhea, difficulty and soreness of urination, azoospermia.

From the cardiovascular system: Thrombocytopenia, phlebitis, leukopenia, anemia, hemorrhage and bleeding.

From the skin: alopecia, scar formation at the injection site, redness, soreness, necrosis of subcutaneous tissue, numbness and hyperemia of the face.

It is also possible to raise the temperature, anaphylactic reactions, increase the concentration of hepatic transaminases, alkaline phosphatase, urea nitrogen in the blood, pain syndrome, flu-like syndrome, the development of infections, cough.

Overdose:

Depression of the bone marrow, bleeding, vomiting, nausea, fever.

Interaction:

With simultaneous administration of attenuated vaccines to a patient, their side effects may increase, while simultaneous administration of inactivated vaccines may reduce their effectiveness.

With simultaneous admission with other myelotoxic drugs and radiation therapy, their negative impact on the bone marrow is enhanced.

Preparations stimulating microsomal liver enzymes (barbiturates, rifampicin, phenytoin) with simultaneous application may enhance the toxic effect of dacarbazine. The use of dacarbazine in combination with 6-mercaptopurine, azathioprine and allopurinol can enhance the effect of the latter and increase their toxicity. Dacarbazine can enhance the action of methoxypsoralene due to photosensitization.

Solution dacarbazine is chemically incompatible with heparin, hydrocortisone, Lcysteine and sodium bicarbonate.

Special instructions:

To dilute the preparation for parenteral administration, sterile water for injection is used, if intravenous, then up to 250 ml of a 5% dextrose solution or 0.9% saline is added to the solution.

Before and during the treatment it is necessary to control the pattern of peripheral blood, the level of urea nitrogen, creatinine, uric acid, liver transaminase activity, lactate dehydrogenase and the concentration of bilirubin in the blood plasma.

Against the background of therapy, it is not recommended to vaccinate patients and their families.

The drug should be administered under the supervision of a doctor who has experience of antitumor therapy.

Instructions

Dacarbazine (Dacarbazinum)