Dacarbazine-LNS lyophilisate solution 200mg, vials 1pc

Composition

1 bottle contains:

 Active substance:

Dacarbazine 200 mg

Auxiliary substances:  

citric acid 200 mg

mannitol 100 mg

Pharmacological action

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

It is assumed that there are three pathways of the mechanism of action of dacarbazine: alkylation due to carbonium ions, suppression of purine bases, and interaction with SH groups. The drug is phase-specific.

 The maximum plasma concentration is usually reached immediately after intravenous use of the drug. Plasma protein binding is very low (about 5%). Penetrates the blood-brain barrier in small amounts. There is no data on its penetration into the placenta and breast milk.

The drug is excreted from the body in two phases with an initial half-life of about 20 minutes and a final half-life of about 5 hours, with impaired liver or kidney functions, these indicators are approximately 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 aminoimidazole carboxamide, which is excreted in the urine. 40% of the drug is excreted unchanged by the kidneys, 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.

Use during pregnancy and lactation

Dacarbazine is contraindicated during pregnancy.

If necessary, use during lactation, breastfeeding should be discontinued.

Women of childbearing age should use reliable methods of contraception.

Experimental studies revealed the toxic effect of dacarbazine on the fetus.

Contraindications

-hypersensitivity to dacarbazine or to any of the auxiliary components of the drug; – severe suppression of bone marrow hematopoiesis; – severe hepatic or renal failure; – pregnancy and lactation. With caution: in case of myelodepression (including on the background of concomitant radiation and chemotherapy), acute infectious diseases of viral (including chickenpox, shingles), fungal or bacterial nature (risk of severe complications and generalization of the process), concomitant radiation therapy.

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 the end of therapy and lasts on average up to 1 week. Recovery of blood counts occurs by the 4th week.

From the digestive system: nausea, vomiting, decreased appetite, stomatitis; rarely-diarrhea, increased activity of “liver” enzymes. Very rarely-hepatonecrosis caused by intrahepatic vein occlusion, possibly with a fatal outcome (as a rule, this syndrome occurred during the 2nd course of treatment). Its symptoms include fever, eosinophilia, abdominal pain, enlarged liver, and shock, the severity of which increases rapidly over several hours or days.

From the nervous system: headache, visual impairment, confusion, severe drowsiness, convulsions, asthenic syndrome, paresthesia, hypesthesia of the facial skin.

From 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 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.

Other: flu-like syndrome, secondary infections, hepatic vein thrombosis, myalgia. With prolonged use, the risk of developing neoplasms increases.

Interaction

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

Dacarbazine may enhance the photosensitizing effect of methoxypsoralene.

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

How to take, course of use and dosage

When choosing the dosage and mode of use of the drug in each individual case, you should use the data from the specialized literature. The drug is administered strictly intravenously.

Doses up to 200 mg / m2 are administered in a slow jet for 1-2 minutes. Higher doses should be given in the form of intravenous infusions for 15-30 minutes. Usually, as monotherapy, dacarbazine is used at a dose of 200-250 mg/m2 daily for 5 days. Repeated courses are conducted at intervals of 3 weeks.

When combined with other cytostatics, dacarbazine is administered at a dose of 100-150 mg / m2 for 4-5 consecutive days with an interval of 4 weeks or 375 mg / m2 every 15 days.

Before use, the drug is diluted with water for injection until a concentration of 10 mg/1 ml is reached.

To obtain an infusion solution, 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.

Overdose

Symptoms: increased suppression of bone marrow hematopoiesis and the severity of dyspeptic disorders. Treatment: symptomatic, specific antidote unknown.

Special instructions

Dacarbazine should be used under the supervision of a physician who has experience with anticancer drugs. During the treatment period and after it, careful monitoring of the peripheral blood picture, liver function and its size is necessary.

Dacarbazine treatment should be discontinued immediately if there is a violation of liver or kidney function, symptoms of hypersensitivity to the drug, or hepatic vein thrombosis.

When the first signs of dacarbazine extravasation appear (burning or soreness at the injection site), the use should be stopped immediately.

The remaining dose should be injected into another vein. Reliable methods of contraception should be used during treatment and for 6 months after. During dacarbazine therapy, vaccination with live pathogens should not be carried out.

Form of production

Lyophilizate for the preparation of a solution for intravenous use

Storage conditions

Store in a dry place, protected from light, at a temperature of 2-8 °C

Shelf life

2 years

Active ingredient

Dacarbazin

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Description

For adults as directed by your doctor

Indications

Cancer