Asparaginase

When ATH:
L01XX02

Characteristic.

Enzyme, produced by strains of E. coli, or derived from, etc.. sources. The purified form of white powder, easily soluble in water, practically insoluble methanol, acetone and chloroform.

Pharmacological action.
Antitumor, cytostatic.

Application.

Acute leukemia lymfoblastnыy, Acute recurrent leukemia myeloblastnыy, T-cell lymphoma, lymphosarcoma, retikulosarkoma.

Contraindications.

Hypersensitivity, abnormal liver function, kidney, pancreas (incl. history), CNS disorders, pregnancy, lactation.

Pregnancy and breast-feeding.

When pregnancy is possible only when necessary (adequate and well-controlled studies in pregnant women were not conducted).

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

At the time of treatment should stop breastfeeding.

Side effects.

Cardio-vascular system and blood (hematopoiesis, hemostasis): lowering the level of clotting factors (V, VII, VIII, IX), fibrinopenia, hypocoagulation, tendency to hemorrhage.

Allergic reactions: rash, hives, anaphylactic shock.

From the digestive tract: anorexia, nausea, vomiting, abdominal pain, malabsorption, pankreonekroz, abnormal liver function.

From the nervous system and sensory organs: headache, irritability, alarm, drowsiness, depression, hallucinations, tremor, coma.

With the genitourinary system: glycosuria, polyuria, proteinuria, acute renal failure.

Metabolism: changes in transaminases, hyperenzymemia, giperglikemiâ, Hyper- or hypolipidemia; hypoalbuminemia, accompanied by edema; azotemia, change in the concentration of uric acid.

Other: chills, the development of infections, hypertonus muscles, arthralgia, respiratory distress syndrome, weight loss, fatal hyperthermia.

Cooperation.

With simultaneous use of vincristine and prednisone side effects are summarized. Weakens the effectiveness of drugs, acting on dividing pools of tumor cells (may reduce or eliminate the anti-tumor effect of methotrexate), violates the detoxification of xenobiotics in the liver.

Overdose.

Symptoms: acute anaphylactic reaction, severe bleeding, acute renal failure, including death.

Treatment: hospitalization, monitoring vital functions; simptomaticheskaya therapy (antipyretic, antihistamines, calcium chloride); if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics.

Dosing and Administration.

B /, / m, intrathecal. The dose is set strictly individually, depending on the nature of the disease, general condition of the patient and his age. Typically administered in / (jet slowly, or drip) at a dose of 150–300 IU/kg daily or every other day. For jet administration, a single dose is dissolved in 10 ml of isotonic sodium chloride solution (slowly and shaking), for drip administration - in 200-500 ml of isotonic sodium chloride solution (should be administered within 30-40 minutes). The course dose for adults is 300,000-400,000 IU, children - reduce according to body weight. Course duration - 3 Sun (in the absence of the effect of the treatment is stopped). / M: 6000–10 000 IU / m² 3 twice a week for 3-4 weeks. When leukemic meningitis, resistant to methotrexate: 3000 IU / m² intrathecal.

Precautions.

Use only under medical supervision, with experience chemotherapy. There must be adequate measures and tools for the diagnosis and treatment of possible complications. To evaluate the clinical effect of the presence of blast cells in peripheral blood and bone marrow of patients with leukemia investigate bone marrow punctate before and after treatment, and patients with gematosarkomoy also measured tumor size. In acute leukemia and generalized forms gematosarkom (in the presence of blasts in peripheral blood and bone marrow) appointed regardless of the peripheral blood, in other cases - when the number of leukocytes in peripheral blood is not less than 3 10⁹ /l, platelets - 100 10⁹ /l. A minimum of 1 once a week to explore the glucose, prothrombin, fibrinogen, bilirubin, cholesterol, total protein, protein fractions, Activity of transaminases, Alkaline phosphatase, diastase and other enzymes. When a sudden change in performance, lowered levels of prothrombin below 60% and fibrinogen concentration less than 3 g / l, increase in clotting time, the development of pancreatitis, treatment should be discontinued and appropriate therapy hold. In order to prevent nephropathy, caused by uric acid (formed by the collapse of large numbers of leukocytes) It recommended the appointment of allopurinol or increased fluid intake, alkalizing urine. In case of contact with skin or mucous membranes must be thorough washing for 15 min water (mucosa) or soap and water (skin). The toxic effect is more pronounced in adults, than in children.

Cautions.

Before treatment is carried out on a sample of individual tolerance: 0,1 ml, contains 10 asparaginase IU, administered s / c in the lateral surface of the shoulder. For control, simultaneously injected side by side 0,1 ml of isotonic sodium chloride solution (result of the reaction is assessed 3 no). With a diameter of not more than papules 1 See the sample is considered negative, and treatment can be initiated. When administered intramuscularly, the volume of the solution should not exceed 2 ml, if the volume is more 2 ml - the dose should be divided. In order to prevent the development of anaphylactoid reactions possible introduction of fractional.

Cooperation