Oncaspar

Onkaspar is an antitumor substance containing the component pegaspargazu, which is formed as a result of the covalent synthesis of natural L-asparaginase, appearing under the action of Escherichia coli, and monomethoxy polyethylene glycol.

In most people with an acute stage of leukemia (especially lymphatic), the survival of malignant cells is determined by the activity of the external source of the L-asparagine element. Healthy cells themselves can synthesize the L-asparagine component, and the effect exerted by the rapid elimination with the help of the enzyme L-asparaginase is weaker in their ratio. It is this unique therapeutic principle that uses the drug - based on an exchange defect during the binding of L-asparagine with certain types of malignant cells.

[1], [2], [3]

Indications Oncaspara

It is used in combination with other anticancer substances for re-induction treatment in the acute stage of leukemia of a lymphoblastic nature, if the patient develops intolerance to the natural forms of the L-asparaginase component.

Release form

The release of the component is in the form of a liquid for IV and IM injection; inside the box is 1 bottle of liquid.

[4]

Pharmacodynamics

Pagaspargaza acts like a natural L-asparaginase - 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 neoplasms lymphoblasts (this distinguishes them from normal cells), because they cannot themselves bind L-asparagine, which they require for stable life activity. When destroyed by the action of pegaspargase of this amino acid inside the blood plasma, the lack of L-asparagine inside the lymphoblasts of the tumor develops. The result is the destruction of protein binding and cell death neoplasms.

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

Pharmacokinetics

Plasma parameters Cmax of pegaspargazy with iv injection correlate with the size of the portion used. The values of the distribution volume of drugs are equivalent to its plasma level.

The term plasma half-life of pegaspargazy is 5.73 ± 3.24 days and is longer than the half-life of natural asparaginase - about 1.28 ± 0.35 days.

After completion of the 60-minute infusion (w / w) of L-asparagine medication inside the blood plasma is not observed; Plasma indicators of L-asparaginase available for registration continue to persist for at least 15 days from the moment of the first administration of pegaspargase.

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

Dosing and administration

Often the drug is used in conjunction with other cytostatics. The drug can be used in consolidating, induction and supporting procedures.

In monotherapy, the substance is used for induction only in the absence of the possibility of using 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 features the patient.

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

In the absence of other medical instructions, the following dosage regimens and treatment regimens are used.

The size of the recommended serving equals 2500 ME (approximately 3.3 ml of medication) / m ², with 14-day intervals.

Children whose body surface is above 0.6 m ² are also used 2500 IU / m ² with a 14-day gap.

For children whose body size is less than 0.6 m ², 82.5 ME each (0.11 ml of substance) / kg is used. After achieving remission, support procedures are carried out, having previously considered the issue regarding the use of Onkaspar in this treatment.

The drug should be injected in / m or in / in the method.

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

With the / in the use of 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 i / m injections, the amount of substance administered at a time should be no more than 2 (children) or 3 ml (adults). If you need to use a higher portion, it is applied through several injections in different areas.

In case of precipitation or cloudiness of the medicinal liquid, it is prohibited to use it. Also, do not shake the substance.

[16], [17]

Use Oncaspara during pregnancy

You can not prescribe Onkaspar during breastfeeding or pregnancy.

There is no data as to whether the substance can pass into the mother's milk, which is why when the need for the introduction of the drug is required, it is necessary to refuse breastfeeding during therapy.

Contraindications

The main contraindications:

• the presence of pancreatitis at the time of initiation of therapy or its history;
• severe hemorrhagic complications arising from treatment with L-asparaginase, present in history;
• history of allergy symptoms (severe) with respect to the active ingredient or auxiliary elements of the medication (laryngeal swelling, generalized form of urticaria, decrease in blood pressure and bronchial spasm), as well as other adverse events associated with the drug and having severe severity.

Side effects Oncaspara

Among the side effects:

• changes in laboratory test data: blood amylase values often increase;
• disorders associated with hemostasis, lymph and circulatory system: myelosuppression often occurs, affecting all 3 sprouts of hemopoiesis (from light to moderate intensity), bleeding, blood coagulation disorder due to changes in protein binding, thrombosis and DIC. About half of thrombosis and severe bleeding develops in the area of cerebral vessels and can cause seizures, and in addition to this stroke with headaches and loss of consciousness. Anemia, which has a hemolytic nature, occurs singularly;
• manifestations affecting the work of NA: often there is a disorder of the CNS activity - a state of depression, a feeling of excitement or confusion, also hallucinations or drowsiness (mild disorders of consciousness), and in addition a change in EEG values (a decrease in α-wave activity and an increase in θ- and δ efficiency - waves) - probably due to the development of hyperammonemia. Occasionally, convulsions and severe disorders of consciousness (for example, coma) or ADHD occur. A single tremor affects the fingers;
• lesions in the gastrointestinal tract: mainly develop disorders of the gastrointestinal tract (mild or moderate) - nausea, diarrhea, anorexia, spastic pain in the abdominal area, vomiting and weight loss. Often, there are also disorders of the exocrine pancreatic activity (diarrhea occurs on their background) and acute pancreatitis. Mumps is sometimes observed. Occasionally, pancreatitis develops, having a necrotic or hemorrhagic nature. Pancreatitis with fatal outcome or accompanied by the acute stage of parotitis, as well as pseudokisty in the pancreatic region is singly noted;
• disorders affecting the urogenital tract: occasional arrester occurs;
• lesions of the subcutaneous tissues and the epidermis: allergy symptoms often develop. TEN is singly observed;
• problems with endocrine function: there are often disorders of endocrine pancreatic activity, in which a ketoacidosis of a diabetic nature develops, and in addition there is a hyperglycemia of the hyperosmolar type;
• metabolic disorders: mainly changes in blood lipid values (an increase or decrease in cholesterol, an increase in VLDL and triglycerides, and in addition an increase in lipoprotein lipase activity and a decrease in LDL values). Typically, these disorders do not cause the development of clinical symptoms. Also, because of extrarenal metabolic disorders, the values of blood urea increase (often) (independent of the serving size). Sometimes hyperuricemia or ammonia occurs;
• infectious or invasive disorders: possible the appearance of infections;
• systemic disorders and signs in the injection area: usually swelling and pain. Often there is pain in the joints, back and abdomen, as well as increased temperature. Occasionally, hyperpyrexia is life-threatening;
• immune manifestations: often there are signs of allergy (hyperthermia, urticaria, myalgia, local erythema, pruritus, shortness of breath and angioedema), tachycardia, anaphylaxis, bronchial spasms and a decrease in blood pressure;
• problems associated with hepatobiliary function: there is mainly a change in the activity of liver enzymes (not dependent on the size of the portion, an increase in the activity of serum transaminases, bilirubin, alkaline phosphatase and LDH) and the development of hepatic fatty infiltration or hypoalbuminemia, which can cause various symptoms, including edema. Occasionally, jaundice, cholestasis, necrosis affecting liver cells, and liver failure, which can cause death, appear.

[15]

Overdose

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

Three thousand IU patients were injected with intravenous 10,000 IU / m ^{2 of} medication. One had a slight increase in serum values of liver transaminases, the second after 10 minutes after the infusion, rashes appeared, disappearing after reducing the speed of the procedure and the use of antihistamines. The third of the participants had no negative symptoms.

[18], [19]

Interactions with other drugs

Due to the decrease in serum indicators of proteins under the influence of pegaspargase, it is possible to increase the toxicity of other agents synthesized with proteins.

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

Pagaspargaza is able to potentiate the toxic effect of other medicines, affecting liver activity.

Pagaspargaza can affect the metabolic processes of other drugs, especially intrahepatic.

The use of pegaspargazy contributes to a change in blood coagulation factors, which increases the likelihood of thrombosis or bleeding. In this regard, Onkaspar should be used with extreme caution in combination with substances that affect platelet aggregation and blood coagulation (dipyridamole, coumarin with aspirin, NSAIDs and heparin).

The introduction of vincristine before using pagaspargazy or together with it causes an increase in toxic activity and increases the likelihood of developing anaphylactic manifestations.

The use of prednisolone along with the drug increases the likelihood of disorders in the blood-clotting system (among those, a decrease in the indices of antithrombin-3, as well as fibrinogen inside the blood serum).

Tsitarbin with methotrexate can develop interaction with pegaspargaza in several ways: with the previous use of these drugs, the effect of pegaspargase is potentiated; if used after medication, an antagonistic decrease in exposure may occur.

When performing vaccination using live vaccines, conducting complex chemotherapy sessions increases the likelihood of pronounced infections, which may also be due to the effect of the disease itself. Because of this, immunization with the use of live vaccines should be at least 3 months after the end of the anticancer treatment cycle.

During therapy with the use of Onkaspar it is forbidden to drink alcohol.

[20]

Storage conditions

Onkaspar is required to keep in a dark place, closed from the penetration of children. It is forbidden to freeze the liquid. Temperature values - in the range of marks 2-8 ° C.

Shelf life

Onkaspar can be used for a 2-year period from the time the therapeutic agent is manufactured.

Analogs

Analogues of the medication are drugs Segidrin, Glytsifon with Boramlanom and Refnot.

[21], [22], [23]