Possible hypersensitivity reactions, including life-threatening anaphylactic reactions, are more common in patients with known hypersensitivity to other forms L-asparhinase. The risk of developing hypersensitivity reactions increases with the increase in the number of doses administered. However, in rare cases, allergic reactions can develop with the first administration of pegasasprasis.
The routine rule should be compulsory observation of the patient within 1 hour after the end of the drug administration and availability of available resuscitative equipment and drugs for the treatment of anaphylaxis (epinephrine, oxygen, glucocorticosteroid preparations, etc.). In case of allergic reactions, the drug should be discontinued immediately and the necessary medical measures taken.
Patients should be informed of possible hypersensitivity reactions to Oncaspar, including the possible rapid development of anaphylactic reactions.
In some patients, the formation of antibodies to pegasparas, which is a foreign protein, can occur without clinical manifestations of hypersensitivity. However, the presence of such antibodies can lead to accelerated inactivation and accelerated elimination of pegasus from the body ("silent inactivation" of pegaspargas). Therefore, during the treatment it is recommended to periodically measure the concentration of the drug in the blood, for example, using the MAAT test system (medac Asparaginase Activity Test).
Negative results of the intradermal tests performed before the start of treatment do not exclude the possibility of the development of anaphylactic reactions.
Within 2-5 hours after the administration of the drug, there may be an increase in body temperature, which in most cases passes spontaneously. Often observed pain in the joints, back, in the abdomen, is usually associated with allergic reactions and pancreatitis.
Pegaspargas can cause from mild to moderate severity myelosuppression of all three hematopoiesis germs; in general, it does not have any clinical significance for the treatment.
When assigning pegasas, you should consider the increased risk of bleeding, especially when combined with drugs that reduce blood clotting (such as acetylsalicylic acid and other non-steroidal anti-inflammatory drugs). Patients should be warned about the inadmissibility of simultaneous use of drugs that also increase the risk of bleeding.
With an increase in the time after completion of treatment, the risk of thrombosis begins to dominate among coagulation disorders. It should be borne in mind that the cause of disorders in the blood clotting system, in addition to pegasasprasis, may be concomitant treatment with other myelosuppressive drugs, as well as the disease itself.
An increased risk of thrombosis has been described in children with mutations of the clotting factor V, resistance to activated protein C or a reduced protein concentration S, antithrombin III or protein C in the blood serum, during asparaginase treatment. In such patients, central venous catheters should be avoided whenever possible, as this may increase the risk of thromboembolic complications. When conducting induction therapy in patients with acute lymphoblastic leukemia, the central venous catheter, if possible, should be installed after the end of the treatment with pegas gas.
Because the pegasgas affects the plasma proteins, it is necessary to carry out regular monitoring of the fibrinogen, prothrombin time and partial thromboplastin time.
In carrying out laboratory monitoring parameters of blood clotting is possible to detect signs of disorders of blood clotting and fibrinolysis, for example, reducing the concentration of fibrinogen, clotting factor IX, XI, antithrombin III, protein C and plasminogen, as well as increase the concentration of von Willebrand factor, plasminogen activator inhibitor type 1 , fragments 1 and 2 of prothrombin, and fibrinogen cleavage products (D-dimers). Fibrinogen can be considered as an indicator of control of the pro- and anticoagulant system. If the concentration of fibrinogen or antithrombin III is significantly reduced, the need for selective substitution therapy should be assessed. Antithrombin III administered by infusion at a dose of 100 minus the current concentration in the serum, measured in percent, a value multiplied by the body weight in kg. Fibrinogen is introduced in the form of fresh-frozen plasma at a dose of 10-15 ml / kg body weight.
Thrombocytopenia and sepsis increase the risk of bleeding.
When combined therapy with Oncaspar is used, the risk of hepatotoxicity must be considered.
In combination with hepatotoxic drugs, Onkaspar should be used with caution, while carefully monitoring the liver function. Particular caution should be shown when prescribing the drug to patients with a history of liver failure.
Violation of protein synthesis can lead to a decrease in the concentration of serum proteins. In most patients, the development of a dose-independent decrease in serum albumin concentration is observed during treatment. Most often violations affect α2 and β fraction of albumin, while the fraction α1 remains unchanged. Since the concentration of serum albumin is essential for the binding and transport of certain drugs, control of serum albumin is necessary, especially in combination chemotherapy. As a result of hypoalbuminemia, edema can develop.
Due to the presence of separate reports on the formation of pancreatic pseudocysts (during the timeup to 4 months after the end of treatment), patients should undergo appropriate examinations (eg, ultrasound) within 4 months after the last injection of pegas gas. Since the exact pathogenesis of pseudocyst formation is not known, in such cases only supportive treatment can be recommended.
In the case of significant changes in the concentration of serum lipids, which may be associated, including the simultaneous administration of glucocorticosteroids (eg triglyceride concentrations greater than 2000 mg / 100 ml), careful clinical observation and standard treatment are recommended in view of the increased risk of pancreatitis.
For early detection of pancreatitis, it is necessary to regularly determine the concentration of amylase in the blood, which can increase during and after the treatment with pegasas. If signs of pancreatitis develop, including an increase in the concentration of amylase, treatment with Oncaspar should be discontinued.
In the treatment with asparaginase preparations, it is possible to develop mumps that are not associated with pancreatitis, the symptoms of which are resolved within a few days after discontinuation of the asparaginase preparation.
Violation of the exocrine function of the pancreas can lead to diarrhea.
Often observed changes in the endocrine function of the pancreas are manifested mainly in the form of violations of glucose metabolism. In this case, both diabetic ketoacidosis and hyperosmolar hyperglycemia can develop, which are usually amenable to treatment with insulin preparations. Possible causes of glucose metabolism disturbances are, on the one hand, a decrease in insulin production due to a violation of protein synthesis under the influence of pegaspargase, on the other hand - a violation of the secretion of insulin or a decrease in the number of insulin receptors. In this regard, in the treatment of pegasasgas, regular monitoring of glucose in the blood and urine should be carried out.
Risk factors for developing hyperglycemia include age over 10 years, overweight, Down's syndrome.
To assess the therapeutic effect, you should constantly monitor the parameters of peripheral blood (with the counting of the formed elements) and the function of the bone marrow.
When combined therapy with Oncaspar is used, it is necessary to take into account the risk of toxicity from the central nervous system.
In rare cases, it is possible to develop a syndrome of reversible leukoencephalopathy. Symptoms of this syndrome are mainly manifested in the form of increased blood pressure, seizures, headache, changes in mental state and acute visual impairment (mainly cortical blindness or cortical hemianopia). Treatment of the syndrome of the posterior reversible leukoencephalopathy is symptomatic. Priority measures in these cases are antihypertensive therapy and arresting seizures with antiepileptic drugs. It is also recommended to reduce the dose or interrupt immunosuppressive drug therapy.
In the course of laboratory studies, in the first days after the initiation of therapy, often a significant decrease in the number of circulating tumor cells (lymphoblasts) is observed, the concentration of leukocytes can be from normal to significantly reduced. In this case, the concentration of uric acid in the blood serum can significantly increase, which is accompanied by a risk of developing uremic nephropathy.
When prescribing Onkaspar, one should take into account the ability of pegasasprogs to provide immunosuppressive action,which can increase the risk of infection.
Patients should use reliable contraceptive methods during Oncaspar treatment.
When dealing with drug Oncaspar care must be taken to avoid contact with skin and mucous membranes, especially getting it in your eyes and inhalation of vapors, as the drug can cause irritation in contact. In case of accidental contact with the skin or mucous membranes, a thorough rinsing of the contact area with a large amount of water should be performed for at least 15 minutes.
After the treatment, the unused preparation, as well as the used materials, must be disposed of in accordance with the rules adopted in the medical institution.