Pegasaspraga - instructions for use, doses, side effects, contraindications

Clinical and pharmacological group: & nbsp

Other antineoplastic agents

Included in the formulation

Onkaspar

solution w / m in / in

medac GmbH Germany

АТХ:

L.01.X.X Other antineoplastic agents

L.01.X.X.24 Pegasaspragase

Pharmacodynamics:Antineoplastice means. Pegasaspraga is the result of covalent binding of native L-asparaginase, synthesized by E. coli, with monomethoxypolyteTyleneglycol (PEG). L-asparaginase catalyzes the cleavage of asparagine. It is believed that for tumor lymphoblasts, unlike healthy cells, this amino acid is irreplaceable, since they are not able to synthesize L-asparagine, necessary for their normal vital activityand. Destruction of the amino acid L-asparagine in the blood plasma by L-asparagine in the blood plasma leads to a deficiency of L-asparagine in tumor lymphoblasts, causes a violation of protein synthesis, as well as DNA and RNA synthesis and death of tumor cells.

Pharmacokinetics:

Peak concentration PEG in the blood plasma after intravenous administration correlates with the administered dose.

The true volume of distribution is equivalent to the established volume of plasma. The half-life is 315-588 h (an average of 10.5 days). It is determined in the plasma for 15 days after the first administration.

Indications:Acute lymphoblastic leukemia (re-induction therapy) with development of hypersensitivityto native forms of asparaginase.

ICD-10

II.C81-C96.C91.0 Acute lymphoblastic leukemia

Contraindications:

Hypersensitivitytion.
Pancreatitis.
Hemorrhagic complications (against asparaginase therapy).
Pregnancy, lactation.

Carefully:Inhibition of hematopoiesis in the background of previous cytotoxic or radiotherapy, chicken pox or herpes zoster, diabetes mellitus, anticoagulant therapy or history of hemostasis disorder, impaired liver function, bone marrow tumor infiltration.

Pregnancy and lactation:

Recommendations FDA category C. Studies in humans and animals have not been conducted. It is recommended to avoid the use of antitumor, especially combined chemotherapy in pregnancy, especially in the first trimester. With the indications, it is necessary to relate the risk and benefit and take into account the mutagenic, teratogenic and carcinogenic potentials of these agents. In view of the potential threat to the fetus, women of childbearing age are recommended to use contraceptives during asparaginase treatment.

There is no information on the penetration into breast milk.Due to the excretion of other antitumor drugs with milk and the potential risk of adverse effects on the child during treatment with pegasus, breastfeeding should be discontinued.

Dosing and Administration:

Intramuscularly and intravenously. For intramuscular administration, the volume of the drug administered simultaneously should not exceed 2 ml for children and 3 ml for adults; If more is needed, several injections should be made at different locations. For intravenous administration, drip for 1 to 2 hours in 100 ml of a 0.9% solution of NaCl or a 5% solution of dextrose.

Adults and children with a body surface area of more than 0.6 square meters are assigned 2.5 thousand IU / m 2 once in 14 days; 82.5 IU / kg body weight is administered to children with a body surface area of less than 0.6 square meters.

Intramuscular administration is preferred because of the reduced risk of hepatotoxicity, coagulopathy, gastrointestinal and renal disorders compared with intravenous administration.

Side effects:

From the nervous system: epistatus, convulsions, drowsiness, coma, malaise, impaired thinking, dizziness, emotional lability, headache, loss of lip sensitivity, paresthesia, parkinsonism syndrome, disorientation.

From the skin: prurit, alopecia, blisters, purpura, depigmentation of the skin of hands, fungal skin lesions, whitening and striation of nails, erythematous rashes, petechial rash.

From the urinary system: hyperammonia, hypercreatininaemia, frequent urination, hematuria, hemorrhagic cystitis, impaired renal function.

From the musculoskeletal system: diffuse and local musculoskeletal pain, arthralgia, tension and stiffness in the joints.

From the digestive system: decreased or increased appetite, constipation, or diarrhea; dyspepsia (flatulence, abdominal pain, inflammation of the mucous membranes of the gastrointestinal tract, colitis, nausea, vomiting); pancreatitis (including lightning and fatal), increased activity of amylase and lipase in the blood serum; violation of liver function (increased activity of "liver" transaminases and GGT, hyperbilirubinemia, jaundice, fatty hepatosis, hepatomegaly, ascites).

On the part of the organs of hematopoiesis and the system of hemostasis: hypofibrinogenemia, lengthening of prothrombin and partial thromboplastin time, reduction of antithrombin III; thrombosis of the superficial and deep veins, thrombosis of the sagittal sinus,thrombosis of venous catheters; hemorrhagic syndrome, increased bleeding, nasal bleeding, ecchymosis; leukopenia, agranulocytosis, pancytopenia, thrombocytopenia, DIC syndrome, hemolytic anemia.

From the respiratory system: cough, upper respiratory tract infection.

From the side of the cardiovascular system: cardialgia, bacterial endocarditis (subacute), increase or decrease in blood pressure, tachycardia, peripheral edema.

Laboratory indicators: hyperglycemia (from mild to severe), hypoglycemia, hyponatremia, urinary nephropathy, hyperuricemia, hypoproteinemia, hypoalbuminemia, proteinuria, metabolic acidosis.

Other: increased sweating at night, malaise, secondary infections, sepsis, septic shock.

Allergic reactions: anaphylactic reactions, bronchospasm, shortness of breath, arthralgia, skin rash, swelling of the lips, chills, hyperthermia.

Local reactions: pain, flushing and inflammation of the skin at the injection site.

Overdose:

The antidote for pegas gas is unknown. Anaphylactic reactions require immediate administration of epinephrine, glucocorticosteroids, antihistamines and the use of oxygen.

Some patients experienced a slight increase in serum liver transaminases; in other patients, after the onset of infusion, a rash appeared, which occurred after slowing the rate of infusion and prescribing antihistamines.

Interaction:

Altrethamine increases the likelihood of complications.

Amiodarone. Against the backdrop of pegasaspasis, the concentration of the free fraction in plasma increases (it is displaced from the bond with proteins) and the effect can increase.

Amitriptyline. Against the backdrop of pegasaspasis, the concentration of the free fraction in plasma increases (it is displaced from the bond with proteins) and the effect can increase.

Anastrozole. Increases (mutually) the likelihood of complications.

Asparaginase increases the likelihood of complications.

Acetylsalicylic acid increases the effect on blood coagulability.

Bicalutamide. Increases (mutually) the likelihood of complications.

Bleomycin. Increases (mutually) the likelihood of complications.

Busulfan. Increases (mutually) the likelihood of complications.

Warfarin. Against the backdrop of pegasaspasis, the concentration of the free fraction in plasma increases (it is displaced from the bond with proteins) and the effect can increase.

Vincristine. Increases (mutually) the likelihood of complications.

Vinorelbine. Increases (mutually) the likelihood of complications.

Gemcitabine. Increases (mutually) the likelihood of complications.

Heparin sodium. Against the background of pegasas, the effect is enhanced; when combined appointment increases the risk of bleeding or thrombosis.

Dakarbazin. Increases (mutually) the likelihood of complications.

Dalteparin sodium. Against the background of pegasas, the effect is enhanced; when combined appointment increases the risk of bleeding and / or thrombosis.

Daunorubicin. Increases (mutually) the likelihood of complications.

Diazepam. Against the backdrop of pegasas, the concentration of the free fraction in the plasma increases (it is displaced from the bond with proteins) and the effect can be intensified.

Diclofenac. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); when combined appointment increases the risk of bleeding and / or thrombosis.

Dipyridamole. Against the backdrop of pegasas, the concentration of the free fraction in the plasma increases (it is displaced from the bond with proteins) and the effect is amplified.

Doxorubicin. Increases (mutually) the likelihood of complications.

Docetaxel. Increases (mutually) the likelihood of complications.

Ibuprofen. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); when combined appointment increases the risk of bleeding and / or thrombosis.

Idarubicin. Increases (mutually) the likelihood of complications.

Imipramine. Against the backdrop of pegasaspasis, the concentration of the free fraction in plasma increases (it is displaced from the bond with proteins) and the effect can increase.

Interferon alfa-2a. Increases (mutually) the likelihood of complications.

Interferon alfa-2b is a human recombinant. Increases (mutually) the likelihood of side effects.

Irinotecan. Increases (mutually) the likelihood of complications.

Ifosfamide. Increases (mutually) the likelihood of complications.

Carboplatin. Increases (mutually) the likelihood of complications.

Carmustine. Increases (mutually) the likelihood of complications.

Ketoprofen. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); combined use increases the risk of bleeding and / or thrombosis.

Ketorolac. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); joint use increases the risk of bleeding and / or thrombosis.

Levamisole. Increases (mutually) the likelihood of complications.

Lomustine. Increases (mutually) the likelihood of complications.

Megestrol. Increases (mutually) the likelihood of complications.

Meloksikam. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); when combined appointment increases the risk of bleeding and / or thrombosis.

Melphalan. Increases (mutually) the likelihood of complications.

Mercaptopurine. Increases (mutually) the likelihood of complications.

Methotrexate. Increases (mutually) the likelihood of side effects. In the process of suppressing protein synthesis and cell replication, the drug can affect the action of methotrexate, the pharmacotherapeutic effect of which requires cellular replication.

Mitoxantrone. Increases the likelihood of complications.

Mitomycin. Increases (mutually) the likelihood of complications.

Nabumethon. Nabumeton increases the effect on blood coagulability (increases the risk of bleeding and / or thrombosis).

Naproxen. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); combined use increases the risk of bleeding and / or thrombosis.

Paclitaxel. Increases (mutually) the likelihood of complications.

Piroxicam. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); combined use increases the risk of bleeding and / or thrombosis.

Procarbazine. Increases (mutually) the likelihood of complications.

Rofecoxib. Increases the effect on blood coagulability (increases the risk of bleeding and / or thrombosis).

Teniposide. Increases (mutually) the likelihood of complications.

Thioguanine. Increases (mutually) the likelihood of complications.

Thiotepa. Increases (mutually) the likelihood of complications.

Topotecan. Increases (mutually) the likelihood of complications.

Toremifene. Increases (mutually) the likelihood of complications.

Flurbiprofen. Against the background of pegasgas, the concentration of free fraction in the blood increases (it is displaced from the connection with proteins); Co-administration increases the risk of bleeding and / or thrombosis.

Chlorambucil. Increases (mutually) the likelihood of complications.

Celecoxib. Increases the effect on blood coagulability (increases the risk of bleeding and / or thrombosis).

Cyclophosphamide. Increases (mutually) the likelihood of complications.

Cisplatinum. Increases (mutually) the likelihood of complications.

Exemestane. Increases (mutually) the likelihood of complications.

Enoxaparin sodium. Against the background of pegasas, the effect is enhanced; when combined, the risk of bleeding and / or thrombosis increases.

Epirubicin. Increases (mutually) the likelihood of complications.

Estramustine. Increases (mutually) the likelihood of complications.

This is eelander. Increases the effect on blood coagulability (increases the risk of bleeding and / or thrombosis).

Etoposide. Increases (mutually) the likelihood of complications.

Special instructions:

In the monotherapy regimen the drug is used only if it is impossible to use other drugs for some reason, included in the scheme of combined treatment.

Intramuscular administration is preferable to intravenous (lower risk of hepatotoxicity, coagulopathy, gastrointestinal and kidney complications).

With polychemotherapy with the use of pegasasprasis, severe toxic damage to the liver and nervous system can occur.

During the treatment it is necessary to monitor the concentration of uric acid, amylase, peripheral blood picture, glycemia, fibrinogen, prothrombin time and partial thromboplastin time, activity of "hepatic" transaminases.

The introduction of pehaspargasis should be carried out under the supervision of a specialist who has experience in the use of antitumor drugs.

It is necessary to monitor the patient for 1 hour after the injection and the availability of affordable resuscitation equipment and drugs for the treatment of anaphylaxis.

Women and men during treatment should use reliable methods of contraception.

When preparing the solution for injection, it is recommended to use gloves (it has irritating effect on contact). Avoid breathing vapor or contact with the skin and mucous membranes, especially the eyes. On contact, rinse immediately with water for 15 minutes.

During the treatment with the drug should avoid drinking alcohol.

Impact on the ability to drive vehicles and manage mechanisms

During the treatment period, be careful when driving vehicles and occupying other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Instructions

Pegasaspraga (Pegaspargasum)