Dacarbazine-LENS, lyophilizate 200 mg

Dacarbazine is an alkylating antitumor agent with a chemical composition of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide. The drug becomes active after metabolism in the liver.

The three pathways of action of dacarbazine are thought to exist: alkylation due to carbonium ions, inhibition of purine bases and interaction with SH groups. The drug is phase specific.

The maximum plasma concentration is usually reached immediately after intravenous administration of the drug. Binding with plasma proteins is very low (about 5%). It passes through the blood-brain barrier in insignificant amounts. There is no data on its penetration into the placenta and the mother’s milk.

The drug is excreted from the body in two phases with the initial half-life of about 20 minutes and the final one – about 5 hours; in case of liver or kidney function disorders these indices are about 55 minutes and 7 hours respectively.

The drug undergoes dimethylation by hepatic microsomal enzymes to form carbon dioxide, which is excreted with exhaled air and aminoimidazolcarboxamide, which is excreted with urine. 40% of the drug is excreted unchanged by kidneys mainly due to glomerular filtration.

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Indications

Active ingredient

Composition

1 vial contains:

Active substance:

Dacarbazine 200 mg

Associates:

citric acid 200 mg

mannitol 100 mg

How to take, the dosage

When choosing the dose and mode of administration of the drug in each individual case, the data from specialized literature should be used. The drug is administered strictly intravenously.

Doses up to 200 mg/m2 are administered slowly by jetting over 1-2 minutes. Higher doses should be administered as intravenous infusions over 15-30 minutes. Usually, as monotherapy, dacarbazine is used in a dose of 200-250 mg/m2 daily for 5 days. Repeated courses are carried out at intervals of 3 weeks.

In combination with other cytostatics dacarbazine is administered in a dose of 100-150 mg/m2 for 4-5 consecutive days at intervals of 4 weeks or 375 mg/m2 every 15 days.

Before administration the drug is diluted with water for injection to reach a concentration of 10 mg/1 ml.

For preparing solution for infusion the freshly prepared solution is diluted in 200-300 ml of 0.9% sodium chloride solution or 5% dextrose solution. Dacarbazine solution should be protected from light.

Interaction

Enhances the effect (including toxic) of phenobarbital, azathioprine, 6-mercaptopurine, allopurinol. Inducers of microsomal liver enzymes (barbiturates, rifampicin, phenytoin) increase the toxic effect of dacarbazine.

Dacarbazine may increase the photosensitizing effect of methoxypsoralen.

Dacarbazine solution is chemically incompatible with heparin, hydrocortisone, L-cysteine and sodium hydrogen carbonate.

Special Instructions

Dacarbazine should be used under the supervision of a physician experienced in the use of antitumor drugs. During and after treatment, peripheral blood counts, liver function and liver size should be monitored closely.

If liver or renal function abnormalities, symptoms of hypersensitivity to the drug or hepatic vein thrombosis occur, treatment with dacarbazine should be stopped immediately.

In case of the first signs of dacarbazine extravasation (burning or soreness at the injection site) the administration should be stopped immediately.

The remaining dose should be injected into another vein. During treatment and for 6 months after treatment, reliable contraceptive methods should be used. Vaccinations with vaccines containing live germs are not allowed during dacarbazine therapy.

Contraindications

Side effects

Hematopoietic disorders: anemia, leukopenia, granulocytopenia, thrombocytopenia. Inhibition of myelopoiesis is a dose-limiting side effect. Leukocytopenia is usually observed on day 14, thrombocytopenia – on day 18 after therapy termination and lasts on average up to 1 week. Recovery of blood parameters occurs by the 4th week.

In the digestive system: nausea, vomiting, decreased appetite, stomatitis; rarely – diarrhea, increased activity of “liver” enzymes. Very rare – hepatonecrosis due to intrahepatic vein occlusion, possibly with fatal outcome (usually this syndrome occurred during the 2nd course of treatment). Its symptoms include fever, eosinophilia, abdominal pain, liver enlargement, and shock, the severity of which increases rapidly over several hours or days.

Nervous system disorders: headache, visual impairment, confusion, pronounced somnolence, seizures, asthenic syndrome, paresthesias, facial skin hypoesthesia.

Reproductive system disorders: amenorrhea, azoospermia.

Allergic reactions: skin rash, facial hyperemia, febrile syndrome, anaphylactic reactions.

Skin and skin appendages: rarely alopecia, hyperpigmentation and photosensitization of the skin.

Local reactions: soreness at the injection site and along the vein. If the drug gets under the skin – sharp pain, necrosis of the surrounding tissues.

Others: flu-like syndrome, accession of secondary infections, hepatic vein thrombosis, myalgia. With long-term use, the risk of developing neoplasms increases.

Overdose

Pregnancy use

Dacarbazine is contraindicated in pregnancy.

Breastfeeding should be stopped if use is necessary during lactation.

Women of childbearing age should use reliable methods of contraception.

Toxic effects of dacarbazine on the fetus have been found in experimental studies.