Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravenous administration in the form of a white or slightly yellowish powder or a porous (caked) mass.
1 f.
dacarbazine 1 g
Excipients: citric acid, mannitol.
Vials of dark glass (1) - packs of cardboard.
Lyophilizate for the preparation of a solution for intravenous administration in the form of a white or slightly yellowish powder or a porous (caked) mass.
1 f.
dacarbazine 100 mg
Excipients: citric acid, mannitol.
Bottles of dark glass (10) - packs of cardboard.
Lyophilizate for the preparation of a solution for intravenous administration in the form of a white or slightly yellowish powder or a porous (caked) mass.
1 f.
dacarbazine 200 mg
Excipients: citric acid, mannitol.
Bottles of dark glass (10) - packs of cardboard.
Lyophilizate for the preparation of a solution for intravenous administration in the form of a white or slightly yellowish powder or a porous (caked) mass.
1 f.
dacarbazine 500 mg
Excipients: citric acid, mannitol.
Vials of dark glass (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Dakarbazin is an anticancer agent of alkylating action, in chemical composition it is 5- (3, 3-dimethyl-1-triazene) -imidazole-4-carboxamide.
The drug becomes active after metabolism in the liver. It is assumed that there are three ways of the mechanism of dacarbazine: alkylation due to carbonium ions, oppression of purine bases and interaction with SH groups. The preparation is phase-specific.
PHARMACOKINETICS
C max in plasma is usually achieved immediately immediately after intravenous administration of the drug. The connection with plasma proteins is very low (about 5%). Penetrates through the blood-brain barrier in small amounts. There is no evidence of its penetration into the placenta and breast milk.
The drug is withdrawn from the body biphasic with an initial T 1/2 of about 20 minutes and the final - about 5 hours, with violations of the liver or kidneys, these indicators are approximately 55 minutes and 7 hours respectively. The drug is dimethylated with hepatic microsomal enzymes to form carbon dioxide, which is excreted with exhaled air, i-aminoimidazolecarboxamide, which is excreted in the urine. 40% of the drug is excreted by the kidneys unchanged, mainly due to glomerular filtration.
INDICATIONS
- melanoma;
- lymphogranulomatosis;
- soft tissue sarcoma (excluding Kaposi's sarcoma).
There are reports of the effectiveness of dacarbazine in combination with other cytostatics in the treatment of osteogenic sarcoma, uterine sarcoma, pleural and peritoneal mesothelioma, small cell lung cancer, thyroid cancer, carcinoid, pheochromocytoma, insulinoma, neuroblastoma and gliomas.
DOSING MODE
When choosing the doses and the mode of administration of the drug in each individual case, one should use the data of the specialized literature.
The drug is administered strictly in / in. Doses up to 200 mg / m 2 are injected slowly slowly for 1-2 minutes. Higher doses should be administered in the form of IV infusions for 15-30 minutes.
Usually as a monotherapy dacarbazine is used in a dose of 200-250 mg / m 2 daily for 5 days. Repeated courses are held at intervals of 3 weeks. When combined with other cytostatics, dacarbazine is administered at a dose of 100-150 mg / m 2 for 4-5 consecutive days with an interval of 4 weeks or 375 mg / m 2 every 15 days.
Before administration, the drug is diluted with water for injection to reach a concentration of 10 mg / 1 ml. To obtain a solution for infusion, a freshly prepared solution is diluted in 200-300 ml of 0.9% sodium chloride solution or 5% dextrose solution. All solutions of dacarbazine should be protected from light.
SIDE EFFECT
On the part of the organs of hematopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia. Oppression of myelopoiesis is a limiting dose, a side effect.Leukocytopenia is usually observed on day 14, thrombocytopenia - on day 18 after the end of therapy and lasts an average of 1 week. Recovery of blood counts occurs by the 4th week.
From the gastrointestinal tract: nausea, vomiting, anorexia, stomatitis. Rarely is diarrhea.
From the liver: rarely - increased activity of liver enzymes. Very rarely - hepatonecrosis, caused by occlusion of intrahepatic veins, possibly with a lethal outcome. As a rule, this syndrome arose during the second course of treatment. Among his symptoms include fever, eosinophilia, abdominal pain, enlargement of the liver and shock, the severity of which rapidly builds up over several hours or days.
From the side of the nervous system: headache, visual impairment, confusion, marked drowsiness, convulsions, asthenic syndrome, paresthesia, facial hypodeses.
From the side of the reproductive system: amenorrhea, azoospermia.
Allergic reactions: skin rash, hyperemia of the facial skin, febrile syndrome, anaphylactic reactions.
From the skin and skin appendages: rarely - alopecia, hyperpigmentation and skin photosensitization.
Local reactions: soreness at the site of injection along the vein. If the product gets under the skin - severe pain, necrosis of surrounding tissues.
Other: influenza-like syndrome, attachment of secondary infections, thrombosis of hepatic veins, myalgia. With prolonged use, the risk of developing neoplasms increases.
CONTRAINDICATIONS
- hypersensitivity to dacarbazine or any of the auxiliary components of the drug;
- severe oppression of bone marrow hematopoiesis;
severe hepatic or renal insufficiency;
- Pregnancy and the period of breastfeeding.
With caution: acute infectious diseases of the viral (including chicken pox, shingles), fungal or bacterial nature (risk of serious complications and generalization of the process), concomitant radiation therapy.
PREGNANCY AND LACTATION
The drug is contraindicated in pregnancy and during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in severe renal failure.
If abnormalities occur on the part of the kidneys, dacarbazine should be discontinued immediately.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in severe hepatic insufficiency.
If abnormalities occur on the part of the liver, dacarbazine should be discontinued immediately.
SPECIAL INSTRUCTIONS
The drug should be administered under the supervision of a doctor who has experience of antitumor therapy.
Given that dacarbazine differs in photosensitivity, solutions of the drug should be stored in a place protected from light.
During the period of treatment and after it, careful monitoring of the picture of peripheral blood, liver function and liver size is necessary.
If there are violations of the function of the liver or kidneys, symptoms of hypersensitivity to the drug or thrombosis of hepatic veins, dacarbazine treatment should be stopped immediately.
When the first signs of extravasation of dacarbazine (burning or soreness at the injection site), the introduction should be immediately stopped. The remaining dose should be injected into another vein.
Women and men, but the time of treatment and within 6 months after it should be used reliable methods of contraception.
During the treatment with dacarbazine, vaccination with vaccines containing live pathogens can not be performed.
OVERDOSE
In case of an overdose, an increase in oppression of bone marrow hematopoiesis and gastrointestinal toxicity should be expected. The specific antidote is unknown.
Treatment is symptomatic.
DRUG INTERACTION
Drugs that stimulate microsomal enzymes of the liver (barbiturates, rimampicin, phenytoin) with simultaneous application can enhance the toxic effect of dacarbazine. The use of dacarbazine in combination with mercaptopurine, azathioprine and allopurinol can enhance the effect of the latter and increase their toxicity.Dacarbazia can enhance the action of methoxypsoralene due to photosensitization.
The solution of dacarbazine is chemically incompatible with heparin, hydrocortisone, L-cysteine ​​and sodium bicarbonate.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored at a temperature not higher than 25 В° C in a place out of the reach of children.
Shelf life - 3 years. Do not use after the expiration date printed on the package.
