Oncaspar

Oncaspar is an antitumor agent containing the component pegaspargase, which is formed as a result of the covalent synthesis of natural L-asparaginase, which appears under the influence of Escherichia coli, and monomethoxypolyethyleneglycol.

In most people with acute leukemia (especially lymphatic), the survival of malignant cells is determined by the activity of an external source of the element L-asparagine. Healthy cells themselves can synthesize the component L-asparagine, and the effect of rapid excretion by the enzyme L-asparaginase is weaker in relation to them. This is the unique therapeutic principle used by the drug - based on the metabolic defect during the binding of L-asparagine to certain types of malignant cells.

[ 1 ], [ 2 ], [ 3 ]

Indications Oncaspara

It is used in combination with other antitumor agents for reinduction treatment in the acute stage of lymphoblastic leukemia if the patient develops intolerance to the relatively natural forms of the L-asparaginase component.

Release form

The component is released in the form of a liquid for intravenous and intramuscular injections; there is 1 bottle of liquid inside the box.

[ 4 ]

Pharmacodynamics

Pegaspargase acts similarly to natural L-asparaginase – it enzymatically destroys the amino acid L-asparagine, which is located inside the blood plasma.

There is an opinion that this amino acid is indispensable for the activity of tumor lymphoblasts (this distinguishes them from normal cells), because they cannot bind L-asparagine themselves, which they need for stable vital activity. When this amino acid is destroyed by pegaspargase in the blood plasma, a deficiency of L-asparagine develops in the tumor lymphoblasts. As a result, protein binding is destroyed and the tumor cells die.

[ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ]

Pharmacokinetics

Plasma Cmax values of pegaspargase after intravenous injection correlate with the size of the portion used. The values of the distribution volume of the drug are equivalent to its plasma level.

The plasma half-life of pegaspargase is 5.73±3.24 days, which is longer than the half-life of natural asparaginase, approximately 1.28±0.35 days.

After completion of a 60-minute infusion (IV) of the drug, L-asparagine is not observed in the blood plasma; plasma L-asparaginase levels available for recording continue to be maintained for at least another 15 days from the moment of the first administration of pegaspargase.

[ 11 ], [ 12 ], [ 13 ], [ 14 ]

Dosing and administration

The drug is often used in combination with other cytostatics. The medication can be used in consolidation, induction and maintenance procedures.

In monotherapy, the substance is used for induction only when it is impossible to use other chemotherapeutic drugs included in complex treatment regimens (for example, methotrexate, doxorubicin with vincristine, daunorubicin and cytarabine) - due to their toxicity, or due to other factors caused by the characteristics of the patient.

The therapy is carried out by a physician with experience in performing chemotherapy, who is aware of all the risks and effects that develop during therapeutic procedures.

Unless otherwise directed by a physician, the dosage regimens and treatment plans described below are used.

The recommended dose size is 2500 IU (approximately 3.3 ml of medicine)/m2 ^, at 14-day intervals.

For children whose body surface area is over 0.6 m2 ^, 2500 IU/m2 is also administered ^with a 14-day interval.

For children with a body surface area of less than 0.6 ^m2, 82.5 ME (0.11 ml of the substance)/kg are used. After achieving remission, maintenance procedures are carried out, having previously considered the issue of using Oncaspar in this treatment.

The medicine should be administered intramuscularly or intravenously.

It is recommended to use intramuscular injections to reduce the likelihood of coagulopathy, hepatotoxicity and disorders associated with the kidneys and digestive activity, compared to intravenous injections.

For intravenous use, the drug is administered using a dropper - the procedure lasts 1-2 hours. The substance is dissolved in 5% dextrose liquid or 0.9% NaCl (0.1 l).

For intramuscular injections, the amount of substance administered at one time should not exceed 2 ml (children) or 3 ml (adults). If a larger dose is required, it is administered through several injections into different areas.

If sediment forms or the medicinal liquid becomes cloudy, it is prohibited to use it. Also, do not shake the substance.

[ 16 ], [ 17 ]

Use Oncaspara during pregnancy

Oncaspar should not be prescribed during breastfeeding or pregnancy.

There is no data on whether the substance can pass into breast milk, which is why, if the drug needs to be administered, breastfeeding should be discontinued during therapy.

Contraindications

Main contraindications:

• the presence of pancreatitis at the time of initiation of therapy or its presence in the anamnesis;
• history of severe hemorrhagic complications resulting from treatment with L-asparaginase;
• history of allergy symptoms (severe) to the active ingredient or auxiliary elements of the medication (swelling of the larynx, generalized urticaria, decreased blood pressure and bronchial spasm), as well as other adverse reactions associated with the medication and having a severe expression.

Side effects Oncaspara

Side effects include:

• changes in laboratory test data: blood amylase levels often increase;
• disorders associated with hemostasis, lymph and the circulatory system: myelosuppression often occurs, affecting all 3 germs of hematopoiesis (from mild to moderate intensity), bleeding, blood clotting disorder due to changes in protein binding, thrombosis and DIC syndrome. About half of thromboses and severe bleeding develop in the area of the cerebral vessels and can cause seizures, as well as stroke with headaches and loss of consciousness. Anemia of a hemolytic nature occurs alone;
• manifestations affecting the work of the nervous system: often there is a disorder of the central nervous system - a state of depression, a feeling of excitement or confusion, as well as hallucinations or drowsiness (moderate disorders of consciousness), and in addition to this, a change in EEG values (decrease in the activity of α-waves and increase in the effectiveness of θ- and δ-waves) - probably due to the development of hyperammonemia. Rarely, convulsions and severe disorders of consciousness (for example, coma) or RPLS occur. Tremor affecting the fingers occurs sporadically;
• Gastrointestinal tract lesions: mainly gastrointestinal disorders (mild or moderate) develop – nausea, diarrhea, anorexia, spastic abdominal pain, vomiting and weight loss. Often, disorders of the exocrine pancreas also appear (diarrhea occurs against their background) and acute pancreatitis. Mumps is sometimes observed. Pancreatitis of a necrotic or hemorrhagic nature develops occasionally. Pancreatitis with a fatal outcome or accompanied by an acute stage of mumps, as well as pseudocysts in the pancreas, are noted isolatedly;
• disorders affecting the urogenital tract: acute renal failure occasionally occurs;
• lesions of subcutaneous tissues and epidermis: allergy symptoms often develop. TEN is observed sporadically;
• problems with endocrine function: disorders of the endocrine activity of the pancreas often occur, in which diabetic ketoacidosis develops, and in addition, hyperglycemia of the hyperosmolar type occurs;
• metabolic disorders: mainly changes in blood lipid levels occur (increase or decrease in cholesterol levels, increase in VLDL and triglyceride levels, and also increase in lipoprotein lipase activity and decrease in LDL levels). Usually, such disorders do not cause the development of clinical symptoms. Also, due to extrarenal metabolic disorders (often), blood urea levels increase (not dependent on the portion size). Sometimes hyperuricemia or -ammonemia occurs;
• infectious or invasive disorders: infections may occur;
• Systemic disorders and signs at the injection site: swelling and pain usually occur. Joint, back and abdominal pain is common, and the temperature increases. Hyperpyrexia, which can be life-threatening, is rare;
• immune manifestations: signs of allergy (hyperthermia, urticaria, myalgia, local erythema, itching, shortness of breath and Quincke's edema), tachycardia, anaphylaxis, bronchial spasms and decreased blood pressure often appear;
• problems related to hepatobiliary function: mainly changes in liver enzyme activity (increase in serum transaminase, bilirubin, alkaline phosphatase and LDH activity independent of the portion size) and development of hepatic fatty infiltration or hypoalbuminemia, which can cause various symptoms, including edema. Rarely, jaundice, cholestasis, necrosis affecting liver cells and liver failure occur, which can lead to death.

[ 15 ]

Overdose

The drug has no antidote. If symptoms of anaphylaxis appear, GCS, epinephrine, and antihistamines should be administered immediately, and oxygen should be used.

Three patients were given 10,000 IU/m2 of the drug intravenously via a drip ^. One patient had a slight increase in serum liver transaminase levels, while the second developed a rash 10 minutes after the infusion, which disappeared after the procedure was slowed down and antihistamines were used. The third participant had no negative symptoms.

[ 18 ], [ 19 ]

Interactions with other drugs

Due to the decrease in serum protein levels under the influence of pegaspargase, the toxicity of other agents synthesized with proteins may increase.

At the same time, the suppression of protein binding and cell replication leads to the fact that pegaspargase can alter the activity of methotrexate, whose therapeutic properties are associated with cell replication processes.

Pegaspargase can potentiate the toxic effect of other medications by affecting liver function.

Pegaspargase may affect the metabolic processes of other drugs, especially intrahepatic ones.

The use of pegaspargase contributes to changes in the indicators of blood coagulation factors, which increases the likelihood of thrombosis or bleeding. In this regard, it is necessary to use Oncaspar with extreme caution in combination with substances that affect platelet aggregation and blood coagulation (dipyridamole, coumarin with aspirin, NSAIDs and heparin).

Administration of vincristine before or together with pegaspargase increases toxic activity and increases the likelihood of developing anaphylactic reactions.

The use of prednisolone together with the drug increases the likelihood of disorders in the blood coagulation system (including a decrease in antithrombin-3 levels, as well as fibrinogen in the blood serum).

Cytarbine with methotrexate can develop interaction with pegaspargase in several ways: with previous use of these drugs, the effect of pegaspargase is synergistically potentiated; in the case of their use after the drug, an antagonistic decrease in effect may occur.

When performing vaccination using live vaccines, conducting complex chemotherapy sessions increases the likelihood of severe infections, which may also be associated with the action of the disease itself. For this reason, immunization using live vaccines should be performed at least 3 months after the end of the antitumor treatment cycle.

During therapy with Oncaspar, it is prohibited to consume alcoholic beverages.

[ 20 ]

Storage conditions

Oncaspar must be stored in a dark place, out of reach of children. It is prohibited to freeze the liquid. Temperature values are in the range of 2-8°C.

Shelf life

Oncaspar can be used for a 2-year period from the date of production of the therapeutic agent.

Analogues

Analogues of the drug are Sehydrin, Glycifon with Boramilan and Refnot.

[ 21 ], [ 22 ], [ 23 ]