- Anticancer agent, enzyme [Other anticancer agents]
|Lyophilizate for solution preparation for intravenous and intramuscular administration||1 dosage|
|excipients: mannitol – 80 mg|
Description of the dosage form
White lyophilized mass.
Pharmacological effect – antitumor.
Asparaginase is an enzyme that catalyzes the cleavage of the amino acid – asparagine – necessary for the life of the cell. The maximum of its proliferation suppression activity is noted in the postmitotic G1 phase of the cell cycle. It appears that the effect 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 disrupted, as well as the synthesis of DNA and RNA.
Cmax in blood plasma is achieved with intravenous administration in the first minutes, with intramuscular administration – after 14-24 hours. Communication with plasma proteins – 30%. Asparaginase penetrates the reticuloendothelial system and is slowly cleaved to inactive substances. T1 / 2 with a / in the introduction is from 8 to 30 hours, with a / m administration – 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. Less than 1% of the administered dosage is determined in the cerebrospinal fluid.
The route of elimination of the drug has not been established. In the urine, the drug appears only in trace amounts.
Indications of the preparation L-Asparaginase
In combination with other drugs, it is used to induce remission in acute lymphoblastic leukemia, as well as to treat lymphoblastic non-Hodgkin’s lymphomas (lympho- and reticulosarcomas).
It is not recommended to use asparaginase as part of maintenance therapy regimens due to the rapid development of resistance to the drug (suppression of the ability of cells to synthesize asparagine).
pancreatitis at present or in history;
previously noted allergic reactions to asparaginase;
pregnancy and lactation period;
severe violations of the liver and kidneys.
With caution: CNS diseases, diabetes mellitus, acute infections (including chickenpox, herpes, herpes zoster), gout (history), nephrolithiasis.
Use during pregnancy and lactation
Use during pregnancy is likely only if necessary (adequate and well-controlled studies in pregnant women have not been conducted).
At the time of treatment should stop breastfeeding.
Allergic reactions: mild hypersensitivity reactions (20-35% of cases) such as rash and / or blisters, arthralgia; sometimes – respiratory failure, anaphylactic shock with a fatal outcome.
The risk of anaphylaxis increases with repeated use. But anaphylactic shock is possible with the first injection. The results of intradermal tests are not completely reliable in predicting allergic reactions.
On the part of the digestive system: anorexia, nausea, vomiting, stomatitis, abdominal pain, malabsorption syndrome, decreased exocrine function of the pancreas, pancreatic necrosis, pseudocyst formation, fatty infiltration of the liver, impaired liver function (increased activity of serum transaminases, alkaline phosphatase, LDH, hyperbilirubinemia, hypoalbuminemia); in rare cases – cholestasis, jaundice.
On the part of the hemostasis system: a decrease in the content of coagulation factors (V, VII, VIII and IX), hypofibrinogenemia, thrombocytopenia, an increase in blood clotting time.
From the genitourinary system: glucosuria, polyuria, proteinuria; very rarely – the development of acute renal failure.
From the side of the central nervous system: headache, depression, pathological drowsiness, increased fatigue, confusion, irritability, anxiety, hallucinations; in some cases, convulsions, tremors, coma, intracranial hemorrhages or thrombosis were noted.
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, a decrease in the level of thyroxine-binding protein.
Others: protein-free edema, immunosuppression, leukopenia, development of infections, muscle hypertonicity, respiratory distress syndrome, weight loss, chills, fever; very rarely – hyperpyrexia; in some cases – hemolytic anemia; described a case of toxic epidermal necrolysis (Lyell’s syndrome).
If any of these side effects worsen or any other side effects that are not listed in the instructions appear, you should inform your doctor about this.
The toxic effect is less pronounced with the introduction of asparaginase after prednisolone and vincristine than with its use before or during the use of these drugs.
Asparaginase has a synergistic or antagonistic effect on methotrexate and cytarabine, depending on the dose and time of use. Preliminary use of methotrexate and cytarabine synergistically enhances the asparaginase outcome. If asparaginase is administered first, its effect may be attenuated by subsequent administration of methotrexate or cytarabine.
Asparaginase may increase the toxicity of other drugs by affecting liver function.
The use of uricosuric anti-gout drugs may increase the risk of uric acid nephropathy.
Alcohol should be avoided during treatment with asparaginase.
Dosage and administration
V / m , in / in the form of infusion (at least 30 minutes).
Asparaginase is used both in monotherapy and in combination with other cytostatics, and therefore, in each individual case, the selection of the dosage, regimen and method of administration should be guided by the data of special literature.
Asparaginase is often given to children and adults at a dose of 6,000–10,000 IU/m2 IV or IM every other day or daily until a total dosage of no more than 400,000 IU is reached.
With the / m method of administration, no more than 2 ml of asparaginase solution should be injected into one place. If you need to administer a higher dosage at the same time, you have to do several injections.
Solution preparation. The powder dissolves in 4 ml of water for injection. In order to avoid the formation of foam, a stream of water should be slowly poured along the inner wall of the bottle, do not shake when dissolving, rotate the bottle.
The prepared solution may be slightly opalescent.
For i / m administration, the prepared solution does not need to be diluted.
For continuous IV infusion, after dissolving 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.
Symptoms: in case of an overdose of asparaginase, the following life-threatening situations may occur – anaphylaxis; hyperglycemic status, which can be stopped by insulin therapy; bleeding disorders, which may require replacement therapy with fresh frozen plasma to reduce the risk of bleeding.
Treatment: hospitalization, monitoring of vital signs, symptomatic therapy. The specific antidote is unknown.
Treatment with asparaginase should be carried out only under the supervision of a physician experienced in anticancer chemotherapy.
Before starting treatment, an individual tolerance test is carried out: 0.1 ml of a solution containing 10 IU of asparaginase is injected s / c into the lateral surface of the shoulder. For control, 0.1 ml of isotonic sodium chloride solution is simultaneously administered nearby (the effect of the reaction is evaluated after 3 hours). If the papule diameter is not more than 1 cm, the test is negative, and treatment can be started.
With the / m administration, 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, fractional administration is advisable. In case of allergic reactions, the administration of asparaginase should be stopped immediately. It is necessary to take appropriate measures: the introduction of antihistamines, GCs and drugs that stabilize hemodynamics.
During treatment, it is necessary to systematically monitor the picture of peripheral blood, liver, kidney, pancreas, blood coagulation system: at least 1 time per 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 blood clotting time, the development of pancreatitis, treatment should be stopped 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 proposed to prescribe allopurinol, increase the intake of fluid that alkalizes urine.
In case of accidental contact of the drug with the skin or mucous membranes, thorough washing for 15 minutes with water (mucous membranes) or soap and water (skin) is necessary.
The toxic effect is more pronounced in adults than in children.
Impact on the ability to drive a car and mechanisms. Some side effects of the drug may adversely affect the ability to drive a car, mechanisms and perform potentially hazardous activities that require increased concentration and speed of psychomotor reactions (especially while taking alcohol).
Lyophilisate for solution preparation for intravenous and intramuscular administration. The drug (10,000 IU of the active substance) in glass vials; 1 fl. in a cardboard box.
JSC “Omutninskaya Scientific Pilot Base” (JSC “ONOPB”), Russia, 612711, Kirov region, Omutninsky district, Vostochny settlement.
Claims of consumers should be sent to the address of the company’s representative office in the Russian Federation: Russia, 612711, Kirov region, Omutninsky district, Vostochny settlement.
Tel.: (83352) 33-4-67; fax: (83352) 33-4-67.
Terms of dispensing from pharmacies
Storage conditions of the drug L-Asparaginase
In a dry, dark place, at a temperature not exceeding 10 °C.
Keep out of the reach of children.
Shelf life of the drug L-Asparaginase
Do not use after the expiry date stated on the package.