Pegfilgrrastim (Pegfilgrastimum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Stimulators of hematopoiesis

Included in the formulation
  • Neuralim®
    solution PC 
    Hoffmann-La Roche Ltd.     Switzerland
    • АТХ:

    L.03.A.A   Colony-stimulating factors

    L.03.A.A.13   Pegfilgrrastim

    Pharmacodynamics:The filgrastim conjugate (colony stimulantfactor) and monomethoxypolyteof the glycols. Binding to specific surface receptors of hematopoietic cells, stimulation of proliferation, differentiation and functional activation of cells.
    Pharmacokinetics:The half-life is 15-80 hours. The clearance decreases with increasing dose, which is due to binding to neutrophil receptors. When the number of neutrophils is restored, the concentration of pegfilgrastim rapidly decreases. The systemic effect is more pronounced with an increase in the number of neutrophils and body weight. Dependence of pharmacokinetics from sex was not revealed.
    Indications:To reduce the length of timeand neutropenia, the incidence of febrile neutropenia and infections manifested by febrile neutropenia, with cytotoxic chemotherapy for malignant diseases.
    ICD-10

    III.D70-D77.D71   Functional disorders of polymorphonuclear neutrophils

    III.D70-D77.D72   Other disorders of white blood cells

    III.D70-D77.D70   Agranulocytosis

    XX.Y40-Y59   Medicinal products, medicines and biological substances that cause adverse reactions during therapeutic use

    Contraindications:
    • Hypersensitivity to E. coli proteins.
    • Hypersensitivity to pegfilgrastimu, filgrastimu or other components of the dosage form.
    • Neutropenia in chronic myelogenous leukemia and myelodysplastic syndromes.
    • Acute leukemia.
    • To increase the doses of cytotoxic chemotherapy is higher than those established in dosing regimens.
    • Simultaneous administration with cytotoxic chemo- and radiotherapy.
    • Pregnancy; the period of lactation.
    • Age to 18 years.
    Carefully:Myeloid malignant tumors and myelodysplasia, mobilization of peripheral stem cells preceded byEncyclopedia of hemopoiesis, sepsis, sickle cellanemia.
    Pregnancy and lactation:

    Recommendations FDA - category C.

    It should be used during pregnancy only in situations where the potential benefit to the mother exceeds the potential risk to the fetus.

    There is no information on the penetration into breast milk.

    Dosing and Administration:Introduce subcutaneously in a dose of 6 mg every 24 hours after each cycle of cytotoxic chemotherapy.
    Side effects:

    From the side musculoskeletal system: weak or moderate pain in the bones (26%), which in most cases pass independently or are stopped by normalanalgesics; often - arthralgia, myalgia, back pain, limbs and neck.

    From the side CNS: often a headache.

    From the side respiratory system: cough, dyspnea, infiltrates in the lungs, impaired breathing function, respiratory distress syndrome.

    From the side hemopoiesis: splenomegaly, pain in the upper left quadrant of the abdomen; rarely - thrombosis of blood vessels; very rarely - rupture of the spleen, leukocytosis.

    From the side digestive system: <1% - nausea.

    From the side organism as a whole: often chest pain (non-cardial), fever.

    From the side laboratory indicators: reversible, weak or moderate clinically insignificant increase in uric acid (7%), APF (10%) and LDH (20%).

    Allergic reactions: anaphylaxis, rash, urticaria, angioedema, dyspnea and hypotension, at the beginning or with subsequent administration. Sometimes the resumption of treatment is accompanied by a relapse of symptoms.

    Local reactions: pain at the injection site.

    Overdose:

    The maximum safe single dose of pegfilgrastim is not defined. In clinical studies, doses up to 300 mg / kg (subcutaneously) without the development of serious side effects.

    Treatment: with clinical symptoms it is possible to carry out leukophoresis

    Interaction:

    Lithium preparations - Potentiate the release of neutrophils; more frequent monitoring of their quantity is required.

    Fluorouracil, other antimetabolites - compatibility studies in humans have not been conducted. In animals, with the administration of filgrastim 0-3 days before the administration of fluorouracil, the incidence of side effects increased.

    Cytotoxic agents - you can not enter pegfilgrastim 14 days before and within 24 hours after the last administration of cytotoxic agents due to the much higher sensitivity of the fissile myeloid precursor cells to them. Studies of the use of pegfilgrastim with chemotherapy, accompanied by delayed myelosuppression (for example, derivatives of nitrosourea, mitomycin), were not carried out.

    Special instructions:

    Do not use in patients with acute leukemia receiving myelosuppressive chemotherapy (safety and efficacy of pegfilgrastim have not been studied).

    Apply only under the supervision of an oncologist or hematologist with experience in the use of G-CSF.

    The safety and efficacy of pegfilgrastim in patients receiving high-dose chemotherapy have not been studied.

    Cough, fever and shortness of breath, combined with radiographic infiltrative changes, impaired lung function, and an increase in the number of neutrophils may serve as signs of respiratory distress syndrome in adults. In this case, depending on the clinical situation, it is necessary to cancel and prescribe the appropriate treatment.

    Individual cases of rupture of the spleen after application of G-CSF are registered, some with fatal outcome.

    It should be possible to rupture the spleen in patients with complaints of pain in the upper left abdomen or in the upper part of the left shoulder.

    Monotherapy with pegfilgrastim does not exclude the development of thrombocytopenia and anemia in the continuation of myelosuppressive chemotherapy in a full dose. It is recommended to regularly determine the number of platelets and hematocrit.

    In patients with sickle-cell anemia, leukocytosis is an unfavorable prognostic factor, so they need to regularly perform a blood test and take into account the possibility of developing splenomegaly and thrombosis of blood vessels.

    Leukocytosis 100 × 109 / L or more is observed in less than 1% of patients receiving filgrastim, is temporary and usually observed 24-48 hours after the administration of the drug in accordance with its pharmacodynamic effects. There are no side effects directly associated with such leukocytosis, not described.

    The safety and efficacy of pegfilgrastim in mobilizing peripheral blood stem cells in patients and healthy donors have not been adequately assessed.

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