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

Clinical and pharmacological group: & nbsp

Included in the formulation

АТХ:

L.01.A.A Analogs of nitrogen mustard gas

Pharmacodynamics:

Cytostatic and cytotoxic effects are due to the ability to alkylate DNA molecules.Alkylation is a covalent bond with heterocyclic nucleotide atoms (purines and pyrimidines). Alkyl groups are attached primarily to the nitrogen atom at the 7th position or to the oxygen atom at the 6th position of the guanine nucleotide, to a lesser extent to the nitrogen and oxygen atoms of the adenine and cytosine molecules. The preparation contains two alkyl compounds, which leads to pathological binding of nucleotides among themselves, even from different DNA chains. Alkylation of guanine can lead to a violation of the coding through "abnormal" base cross-linking with thymine or to depurinization (removal of guanine residues). This effect leads to breakage of the DNA strand through the breakdown of the sugar-phosphate backbone of the DNA. It is also possible to form a cross-link between the nucleic acid and the protein. As a result, alkylation of DNA molecules with the subsequent formation of cross-links and ruptures leads to a violation of its matrix functions in the process of replication and transcription. The dividing cells are most sensitive to the damaging effect of alkylating agents. In addition, LS has its own mutagenic and carcinogenic effect.

Pharmacokinetics:

Not studied.

Indications:

Multiple myeloma, testicular semenoma (especially in the presence of metastases), ovarian, breast, reticulosarcoma, malignant angioendothelioma, Ewing sarcoma.

In combination with demekolcinom for cancer of the esophagus and stomach.

ICD-10

II.C81-C96.C90.0 Multiple myeloma

II.C81-C96.C90 Multiple myeloma and malignant plasma cell neoplasms

II.D10-D36.D27 Benign neoplasm of ovary

II.C76-C80 Malignant neoplasms of inaccurately designated, secondary and unspecified locations

II.C73-C75.C75 Malignant neoplasm of other endocrine glands and related structures

II.C60-C63.C63 Malignant neoplasm of other and unspecified male genital organs

II.C60-C63.C62 Malignant neoplasm of testis

II.C51-C58 Malignant neoplasms of female genital organs

II.C81-C96.C83.9 Diffuse non-Hodgkin's lymphoma, unspecified

II.C81-C96.C83.6 Lymphoma is undifferentiated (diffuse)

II.C81-C96.C83.5 Lymphoma (diffuse)

II.C81-C96.C83.3 Lymphoma of large cell (diffuse) - reticulosarcoma

II.C81-C96.C82.9 Follicular non-Hodgkin's lymphoma, unspecified

II.C81-C96.C82 Follicular [nodular] non-Hodgkin's lymphoma

II.C15-C26.C16 Malignant neoplasm of stomach

II.C15-C26.C15 Malignant neoplasm of esophagus

Contraindications:Terminal stages of diseases, cachexia, severe anemia, leukopenia (below 4 · 10⁹/ l), thrombocytopenia (below 150 · 10⁹/ l), severe damage to the liver, kidneys and cardiovascular system.

Carefully:

If the effect is absent after taking 0.1-0.15 g, further use of this drug is inadvisable due to insensitivity to this tumor.

In the process of treatment, you must carefully monitor the blood picture. The drug is stopped when the number of leukocytes in the blood decreases to (2.5-3) · 10⁹/ l, as well as with expressed thrombocytopenia (below 100 · 10⁹/ l). At the end of the course of treatment, it is necessary to determine the number of leukocytes in the blood before each injection of sarcolysin.

After the end of sarcolysin administration, the number of leukocytes can continue to decrease for another 1-2 weeks. If necessary, resort to blood transfusion (1-2 times a week for 100-125 ml).

If the patient was treated with radiotherapy, then capcolysin is used no earlier than 1 month after the end of treatment; the drug is prescribed in these cases in reduced doses.

Pregnancy and lactation:

The category of FDA recommendations is not defined.

Controlled studies in humans have not been conducted. In view of the potential threat to the fetus (side effects, mutagenicity, carcinogenicity and teratogenicity), women of childbearing age are recommended to use contraceptives during treatment with sarcolysine. Possible development of fetal side effects observed in adults. It is recommended to avoid the use of antitumor, especially combined chemotherapy in pregnancy, especially in the first trimester. In the presence of indications, it is necessary to relate the risk and benefit and take into account the mutagenic, carcinogenic and teratogenic potential of these agents.

Dosing and Administration:

Inside or in / in appoint once a week. A single dose for an adult with a body weight of 60-70 kg is 0.04-0.05 g (40-50 mg); for patients with a body weight of 50 kg and less, as well as children - at a rate of 0.5-0.7 mg / kg. In the first 2 doses give 0.05 g, then - 0.03 g. The course of treatment lasts 4-7 weeks.

When metastases of tumors in serous membranes with effusion into the abdominal or pleural cavity, a solution of sarcolysin in the cavity can be injected: from 0.04 to 0.1 g, dissolved in 20-50 ml of isotonic sodium chloride solution, into the abdominal cavity, once a week; in the pleural cavity 0.02-0.08 g, dissolved in 10-20 ml isotonic sodium chloride solution, also once a week.

Before the introduction of a solution of sarcolysin in the cavity, the exudate is removed, then 60-70 ml of a 1% solution of procaine is injected for anesthesia, after which, without removing the trocar from the abdominal cavity or the needle from the pleural cavity, the patient is given a prone position and, after 10 minutes, , 3-0.5 mm freshly prepared sarcolysin solution. The course of treatment usually 4-5 injections. Often, after 2-3 injections, resorption or a decrease in the amount of exudate occurs; injections, however, continue. In total, 0.16-0.2 g (160-200 mg) of sarcolysine is used for the course.

Sarcolysin can also be used for regional chemotherapy; at perfusions of tumors of extremities with use of an extracorporeal circulation apply a preparation in a dose of 25-40 mg on 1 sm³ tissues of the perfused area.

Side effects:

Inhibition of hematopoiesis with a decrease in the number of leukocytes, especially neutrophils, in the blood.

When re-nausea and vomiting appear during treatment, they are prescribed to stop them 1 hour before the administration of sarcolysin chlorpromazine (0.025 g by mouth), perphenazine or other anti-emetics.

When sarcolysin is injected into the cavity, pain, nausea, vomiting may occur; these phenomena usually pass by themselves.To prevent these complications, prior to the administration of sarcolysin, a local anesthetic of the pleura (or peritoneum) should be performed.

Overdose:In case of drug overdose and deep leukopenia (2 · 10⁹/ l and below), neutropenic and thrombocytopenia may cause an increase in body temperature, stomatitis, and symptoms of hemorrhagic diathesis. To prevent infection, you should use benzylpenicillin, to transfuse blood, to introduce leukocyte and thrombocyte mass; when symptoms of agranulocytosis are prescribed in / m sodium nucleate, as well as inside pentoxyl, leukogen.

Interaction:If the combination is applied simultaneously metamizole sodium + quinine with sarcolysin increases the risk of developing leucopenia.

Special instructions:

To obtain a solution, 10-20 ml isotonic sodium chloride solution is introduced into the vial; To accelerate the dissolution, the vial should be heated in water from +60 to +70 ° C.

Instructions

Sarcolysin (Sarcolysinum)