Vero-Asparaginase (Vero-Asparaginase)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAsparaginaseAsparaginase
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  • L-Asparaginase
    lyophilizate w / m d / infusion 
    OMUTNINSK SCIENTIFIC EXPERIMENTAL-INDUSTRIAL BASE, OJSC     Russia
  • Asparaginase medak
    lyophilizate w / m in / in 
    medac GmbH     Germany
  • Vero-Asparaginase
    lyophilizate w / m in / in 
    LENS-PHARM, LLC     Russia
    • Dosage form: & nbsplyophilizate for the preparation of solution for intravenous and intramuscular administration
    Composition:

    1 bottle contains:

    active substance: L-asparhynase 10000 ME

    Excipients: glycine (aminoacetic acid), mannitol.

    Description:

    A porous mass of white color.

    Pharmacotherapeutic group:Antitumor agent - enzyme
    ATX: & nbsp

    L.01.X.X   Other antineoplastic agents

    L.01.X.X.02   Asparaginase

    Pharmacodynamics:Asparaginase is an enzyme that catalyzes the cleavage of the amino acid - asparagine, necessary for the vital activity of cells. The maximum of its activity in suppressing proliferation is noted in the postmitotic G1phase of the cell cycle. It is believed that the action of asparaginase is based on a decrease in the level of asparagine in leukemic tumor cells, which, unlike normal cells, are not able to synthesize their own asparagine. As a result, protein synthesis is destroyed, as well as DNA and RNA synthesis.
    Pharmacokinetics:

    The maximum concentration in blood plasma is achieved with intravenous administration in the first minutes, with intramuscular injection - after 14-24 hours. 30% of the drug binds to plasma proteins. Asparaginase penetrates into the reticulo-endothelial system and slowly decomposes to inactive substances. The half-life with intravenous administration varies from 8 to 30 hours, with intramuscular injection it is 39-49 hours.

    With daily use of the drug it is possible to maintain its sufficient level in the blood, and traces of the enzyme can be detected in the blood plasma for another 10 days after the end of the course of treatment. In cerebrospinal fluid, less than 1% of the administered dose is determined.

    The route of excretion of the drug is not established. In urine, the drug appears only in trace amounts.

    Indications:

    Asparaginase in combination with other agents is used to induce remission in acute lymphoblastic leukemia, as well as for the treatment of lymphoblastic non-Hodgkin's lymphomas. Use asparaginase as part of maintenance therapy is not recommended due to the rapid development of resistance to the drug (suppression of the ability of cells to synthesize asparagine).

    Contraindications:

    - Pancreatitis currently or in history

    - Previously noted allergic reactions to asparaginase

    - Pregnancy and lactation

    - Pronounced violations of the liver and kidneys

    Carefully:Central nervous system diseases, diabetes mellitus, acute infections (including chicken pox, herpes, shingles), gout (in anamnesis), nephrolithiasis.
    Dosing and Administration:

    Asparaginase is used both in monotherapy and in combination with other cytostatics, and therefore, in each individual case, when selecting the dose, regimen and method of administration, reference should be made to the literature.

    The drug is administered intravenously in the form of infusion (at least 30 minutes), or intramuscularly.

    Usually, asparaginase is prescribed for children and adults in a dose of 6 000-10 000 IU / m2 surface of the body intravenously or intramuscularly every other day or every day until a total dose of no more than 400,000 ME.

    With intramuscular route of administration, no more than 2 ml of asparaginase solution should be administered to one site. If it is necessary to introduce a higher dose at the same time, several injections are necessary.

    Preparation of the solution

    The powder is dissolved in 4.0 ml of water for injection.In order to avoid the formation of foam, the water jet should be slowly poured into the inner wall of the vial, do not shake while dissolving, or rotate the vial.

    The prepared solution may slightly opalescent.

    For intramuscular administration, the prepared solution should not be diluted.

    For prolonged intravenous infusion, after dissolution according to the instructions, the calculated amount of asparaginase should be diluted in 250-500 ml of 0.9% sodium chloride solution or 5% dextrose solution.

    Side effects:

    Allergic reactions: light hypersensitivity reactions (20-35% of cases) such as rashes and / or blisters, arthralgia. Sometimes - respiratory failure, anaphylactic shock with a lethal outcome.

    The risk of anaphylaxis increases with repeated use. However, anaphylactic shock is possible even with the first administration. Results of intradermal tests are not completely reliable in predicting allergic reactions.

    From the digestive system: nausea, vomiting, anorexia, stomatitis, malabsorption syndrome, abdominal pain; decrease in the exocrine function of the pancreas, pancreonecrosis, pseudocyst formation; fatty liver infiltration,impaired liver function (increased activity of serum transaminases, alkaline phosphatase, LDH, hyperbilirubinemia, hypoalbuminemia), in rare cases - cholestasis, jaundice.

    From the side of the hemostasis system: decrease in the content of coagulation factors (V, VII, VIII and IX), hypophybrinogenemia, thrombocytopenia, increase in clotting time.

    From the genitourinary system: glucosuria, polyuria, proteinuria, very rarely - the development of acute renal failure.

    From the central nervous system: headache, depression, pathological drowsiness, fatigue, confusion, irritability, anxiety, hallucinations; in some cases, convulsions, tremors, coma, intracranial hemorrhage, or thrombosis.

    From the side of metabolism: decreased glucose tolerance and decreased insulin levels, hyperglycemia, hyperammonemia, ketoacidosis, hyperuricemia, azotemia (not associated with impaired renal function), hyper- or hypolipidemia, rarely-hypothyroidism, decreased thyroxine-binding protein level.

    Other: protein-free edema, immunodepression, leukopenia, development of infections, muscle hypertonicity,respiratory distress syndrome, weight loss, chills, fever, very rarely hyperpyrexia, in some cases - hemolytic anemia; a case of toxic epidermal necrolysis (Lyell's syndrome)

    Overdose:

    In case of an overdose with asparaginase, the following life threatening situations may occur:

    - anaphylaxis;

    - Hyperglycemic status, which can be stopped by insulin therapy;

    - bleeding disorders that may require replacement therapy with freshly frozen plasma to reduce the risk of bleeding.

    The specific antidote is not known. Treatment: hospitalization, monitoring of vital functions, symptomatic therapy.

    Interaction:

    The toxicity is less pronounced with asparaginase after prednisolone and vincristine than with its use before or during the administration of these drugs. Asparaginase has on methotrexate and cytarabine, depending on the dosage and the moment of application, a synergistic or antagonistic effect. Preliminary application of methotrexate and cytarabine synergistically enhances the effect of asparaginase. If asparaginase is introduced first, this effect may be weakened by the subsequent administration of methotrexate or cytarabine. Asparaginase can increase the toxicity of other drugs, affecting liver function. The use of uricosuric antidotal drugs may increase the risk of nephropathy associated with increased uric acid formation.

    During the treatment with asparaginase, alcohol should be avoided.

    Special instructions:

    Treatment with asparaginase should be performed only under the supervision of a specialist who has experience in carrying out antitumoral chemotherapy.

    Before the beginning of treatment, a sample for individual tolerance is carried out: 0.1 ml of a solution containing 10 ME asparaginase, injected subcutaneously into the lateral surface of the shoulder. To control at the same time, 0.1 ml of isotonic sodium chloride solution is injected (the result of the reaction is evaluated after 3 hours). With a papule diameter of not more than 1 cm, the sample is considered negative and treatment can be started.

    With intramuscular injection, the volume of the solution should not exceed 2 ml, if the volume is more than 2 ml - the dose should be divided.

    To prevent the development of anaphylactoid reactions, a fractional administration is advisable.

    In the case of allergic reactions, the administration of asparaginase should be stopped immediately. It is necessary to take appropriate measures: the introduction of antihistamines, glucocorticoids and drugs that stabilize hemodynamics.

    During treatment requires systematic monitoring of peripheral blood picture, liver function, kidney, pancreas, blood coagulation system: not less than 1 times a week to examine the contents of glucose, prothrombin, fibrinogen, bilirubin, cholesterol, total protein, protein fractions, transaminases, alkaline phosphatase, amylase and other enzymes. When a sudden change of these parameters, as well as lowering the prothrombin level of below 60% and fibrinogen concentration of less than 3 g / l, increasing clotting time, pancreatitis development treatment should be discontinued and make the necessary therapy.

    To prevent the development of nephropathy associated with increased production of uric acid from the dissolution of a large number of leukocytes, recommended assignment allopurinol, increased fluid intake, urine alkalizing.

    In case of accidental contact with the skin or mucous membranes, a thorough rinse for 15 minutes with water(mucous membranes) or water with soap (skin).

    Toxic effects are more pronounced in adults than in children.

    Effect on the ability to drive transp. cf. and fur:

    Some side effects of the drug may adversely affect the ability to drive and perform potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions (especially with simultaneous intake of alcohol).

    Form release / dosage:

    Liofilizate for the preparation of a solution for intravenous and intramuscular injection of 10,000 ME in glass bottles.

    Packaging:

    1 bottle with instructions for use in a cardboard pack.

    For 5 or 10 bottles in a cardboard bundle with partitions or special nests along with instructions for use.

    For 30, 50, 85 or 100 vials with instructions for use, one instruction per 10 vials in a carton (for hospitals).
    Storage conditions:In a place protected from light and inaccessible to children, at a temperature not exceeding 10 ° ะก.
    Shelf life:3 years.

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

    The prepared solution is suitable for 6 hours.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-002528/07
    Date of registration:31.08.2007 / 12.08.2016
    Expiration Date:Unlimited
    The owner of the registration certificate:LENS-PHARM, LLC LENS-PHARM, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp30.01.2017
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