Active substanceDacarbazineDacarbazine
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  • 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
  • Dosage form: & nbsplyophilizate for the preparation of a solution for intravenous administration
    Composition:

    1 bottle contains:

    Active substance: dacarbazine 100 mg or 200 mg.
    Excipients: citric acid, mannitol.
    Description:Freeze-dried white or light yellow color
    Pharmacotherapeutic group:An antitumour agent, an alkylating compound
    ATX: & nbsp

    L.01.A.X   Other alkylating preparations

    L.01.A.X.04   Dacarbazine

    Pharmacodynamics:

    Dakarbazine is an antitumor 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, releasing diazomethane. It is assumed that there are three ways of the mechanism of action of dacarbazine: alkylation due to carbonium ions, oppression of purine bases and interaction with SH groups. The preparation is phase-specific.

    Pharmacokinetics:

    The maximum concentration in the plasma is usually achieved immediately after intravenous administration of the drug. The connection with plasma proteins is 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    The drug is withdrawn from the body biphasic with an initial half-life of about 20 minutes and the final - about 5 hours, with violations of the liver or kidneys, these indicators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 with the formation of carbon dioxide, which is excreted with exhaled air and 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 the Kalosha sarcoma)
    There are reports of the effectiveness of dacarbazine in combination with other cytostatics in the treatment of osteogenic sarcoma, sarcoma of the uterus, pleural mesothelioma and peritoneum, small cell lung cancer, thyroid cancer, carcinoid, pheochromocytoma, insulinoma, neuroblastoma and glioma.
    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.

    Carefully:In case of myelosuppression (including concomitant radiation and chemotherapy), 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 .
    Dosing and Administration:

    The drug is administered only intravenously. Doses and mode of administration of the drug are selected individually.

    Doses up to 200 mg / m2 injected slowly for 1-2 minutes. Higher doses should be administered in the form of intravenous infusions for 15-30 minutes. Usually as a monotherapy dacarbazine used in a dose of 200-250 mg / m2 daily for 5 days; You can also instead of the 5-day course, administer the drug once in a dose of 850 mg / m2. Repeated courses are held at intervals of 3 weeks.

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

    Before administration, the drug is diluted with water for injection to reach a concentration of 10 mg / ml.To obtain a solution for infusion, a freshly prepared solution is diluted in 200-300 ml with 0.9% sodium chloride solution or 5% dextrose solution. A solution of dacarbazine should be protected from light.

    If the liver and / or kidney function is impaired, a dose reduction may be required.
    Side effects:

    Side effects are classified by frequency: Very often (1/10); often (1/100, 1/10); infrequently (≥1 / 1,000, 1/100); rarely (≥1 / 10,000, 1 / 1,000); rarely (1/10,000).

    From the hematopoiesis: often - 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.

    On the part of the digestive system: often - nausea, vomiting, decreased appetite, stomatitis. Rarely - diarrhea, increased activity of "liver" enzymes. Very rarely - hepatonecrosis caused by occlusion of intrahepatic veins, possibly with a lethal outcome (as a rule, the syndrome was noted 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 urinary system: infrequently - an increase in the content of creatinine and urea in the urine.

    From the nervous system: infrequently - headache, blurred vision, confusion consciousness, pronounced drowsiness, convulsions, asthenic syndrome, paresthesia, hypoesthesia of the facial skin.

    On the part of the reproductive system: often - amenorrhea, azoospermia.

    Allergic reactions: very rarely - skin rash, hyperemia of the skin of the face, febrile syndrome, anaphylactic reactions.

    From the skin and skin: rarely - alopecia, hyperpigmentation and skin photosensitization.

    Local reactions: infrequent - soreness in the place of injection and along the vein; rarely - with getting the drug under the skin - severe pain, necrosis of surrounding tissues.

    Other: infrequently - influenza-like syndrome, attachment of secondary infections, thrombosis hepatic veins, myalgia; at long-term application of increased risk development of neoplasms.

    Overdose:

    Symptoms: increased oppression of bone marrow hematopoiesis and severity of dyspepsia.

    Treatment: symptomatic, specific antidote is unknown.

    Interaction:

    Drugs that induce microsomal liver enzymes (barbiturates, rifampicin, phenytoin) with simultaneous application can enhance the metabolism of dacarbazine.

    The use of dacarbazine in combination with mercaptopurine, azathioprine and allopurinol increases the effect of the latter and increases their toxicity.

    Dacarbazine can enhance the photosensitizing effect of methoxypsoralen.

    A solution of dacarbazine is chemically incompatible with heparin, hydrocortisone, cysteine ​​and sodium hydrocarbonate.

    Compatible with other antitumor drugs (bleomycin, cisplatin, 5-fluorouracil, vincristine and others) and prednisolone.

    Special instructions:

    Dakarbazine should be used under the supervision of a doctor who has experience with antitumor drugs.

    During the period of treatment and after it, control of the picture of peripheral blood, kidney function, liver function and its 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.

    Whenthe appearance of the first signs of extravasation of dacarbazine (burning or soreness at the injection site) should be stopped immediately. The remaining dose should be injected into another vein.

    During treatment and within 6 months after its termination, reliable methods of contraception should be used.

    During the treatment with dacarbazine, vaccination with vaccines containing live pathogens can not be performed.

    Effect on the ability to drive transp. cf. and fur:In the event of such adverse reactions from the nervous system, like confusion, headache, drowsiness, convulsions, one should refrain from driving and other activities requiring increased concentration of attention.
    Form release / dosage:

    Lyophilizate for the preparation of a solution for intravenous administration of 100 mg, 200 mg.

    Packaging:

    Lyophilizate for the preparation of a solution for intravenous administration of 100 mg or 200 mg in bottles of dark glass sealed with chlorobutyl stopper and coated with an aluminum cap with polypropylene lid type "flip-off"white (100 mg) or green (200 mg) color.

    For 1 or 10 vials with instructions for use in a cardboard pack.

    Storage conditions:
    Lyophilizate: at a temperature of no higher than 25 ° C, in a place protected from light.
    Prepared solution: at a temperature of no higher than 25 ° C, in a place protected from light no more than 8 hours; at a temperature of 5 ° C, in a place protected from light not more than 24 hours.
    Keep out of the reach of children!
    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015602 / 01
    Date of registration:17.03.2009
    Expiration Date:Unlimited
    The owner of the registration certificate:Pliva-Lahema, AOPliva-Lahema, AO Czech Republic
    Manufacturer: & nbsp
    PLIVA-LACHEMA, a.s. Czech Republic
    Representation: & nbspIZVARIN PHARMA LLC IZVARIN PHARMA LLC Russia
    Information update date: & nbsp17.03.2017
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