L-Asparaginase (L-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 solution for infusion and intramuscular injection
    Composition:

    1 bottle contains:

    Active substance:

    L-asparaginase obtained as a result of a continuous cycle by biosynthesis in E. Coli cells (strain D6661) - 10000 ME

    Excipient: mannitol - 80 mg.

    Description:White lyophilized mass.
    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 the cell. The maximum of its activity to suppress proliferation is noted in the postmiotic 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. Connection with plasma proteins - 30%. Asparaginase penetrates into the reticulo-endothelial system and slowly decomposes to inactive substances. Period elimination half-life with intravenous administration is from 8 to 30 hours, with intramuscular injection - 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 (lympho- and reticulosarcoma). 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 is currently or in the anamnesis.

    - Previously noted allergic reactions to asparaginase.

    - Pregnancy and lactation.

    - Expressed violations of the liver and kidneys.

    Carefully:

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

    Pregnancy and lactation:

    Contraindicated in pregnancy and during lactation.

    When pregnancy is possible only if necessary (adequate and strictly controlled studies in pregnant women are not conducted).

    For the duration of treatment, breastfeeding should be discontinued.

    Dosing and Administration:

    Asparaginase is used both in monotherapy and in combination with other cytostatics, in connection with which dissolution is not shaken, 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 given above, 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: lungs hypersensitivity reactions such as rashes and / or blisters, arthralgia. Sometimes - respiratory insufficiency, anaphylactic shock with 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: anorexia, nausea, vomiting, stomatitis, abdominal pain, malabsorption syndrome; decrease in the exocrine function of the pancreas, pancreonecrosis, pseudocyst formation; fatty liver infiltration, impaired liver function (increased activity of serum transaminases, alkaline phosphatase, lactate dehydrogenase, hyperbilirubinemia, hypoalbuminemia), in rare cases - cholestasis, jaundice.

    On the part of the system of hemopoiesis: 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, increased fatigue, confusion, irritability, anxiety, hallucinations; in some cases, convulsions, tremors, coma, intracranial hemorrhage, or thrombosis.

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

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

    If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

    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 synergistic or antagonistic action. 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 formation of uric acid.

    During the treatment with asparaginase, alcohol should be avoided.

    Special instructions:

    Treatment with asparaginase should be done only under the supervision of a doctor who has experience in carrying out anti-tumor 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 into the room (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 the treatment, a systematic control of the picture of peripheral blood, the function of the liver, kidneys, pancreas, blood coagulation system is necessary: ​​at least once a week to examine the content of glucose, prothrombin, fibrinogen, bilirubin, cholesterol, total protein, protein fractions, transaminase activity, alkaline phosphatase, amylase and other enzymes.

    With a sharp change in these indicators, as well as a decrease in the level of prothrombin below 60 % and a fibrinogen concentration of less than 3 g / l, an increase in clotting time, the development of pancreatin treatment should be discontinued and the necessary therapy should be carried out.

    To prevent the development of nephropathy associated with increased formation of uric acid as a result of the breakdown of a large number of leukocytes, it is recommended that allopurinol is administered, an increase in the intake of the liquid basifying urine.

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

    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, manage machinery and perform potentially dangerous types of activities that require an increased concentration of attention and speed of psychomotor reactions (especially with the simultaneous intake of alcohol).

    Form release / dosage:Lyophilizate for the preparation of a solution for infusion and intramuscular injection of 10,000 IU in glass bottles.
    Packaging:1 bottle with instructions for use in a cardboard pack.
    Storage conditions:

    In a dry, dark place at a temperature of no higher than 10 ° C. Keep out of the reach of children.

    Shelf life:

    2 years.

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

    Terms of leave from pharmacies:On prescription
    Registration number:LP-000579
    Date of registration:02.09.2011
    Expiration Date:02.09.2016
    The owner of the registration certificate:OMUTNINSK SCIENTIFIC EXPERIMENTAL-INDUSTRIAL BASE, OJSC OMUTNINSK SCIENTIFIC EXPERIMENTAL-INDUSTRIAL BASE, OJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp19.09.2017
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