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Pharmacology: Human G-CSF is a glycoprotein that regulates production and release of functional neutrophils from bone marrow. Leuco-Plus 300 (Vial/Prefilled Syringe) contains r-met-Hu-G-CSF (Filgrastim) that increases considerably neutrophil count in peripheral blood at 24 hours and minimally monocyte count. It also induces a mild increase of circulating eosinophils and basophils with respect to the initial values in some patients with severe chronic neutropenia; some of these patients show eosinophils or basophils even before treatment. Neutrophils increase depends on the dose, when the recommended dosage is applied. Neutrophils produced in response to treatment show a normal or superior than usual function, according to chemotactic and phagocytic function tests. After interrupting treatment count of circulating neutrophils is reduced in 50% in 1-2 days and it normalizes in a period of 1 to 7 days.
The rapid systemic depuration rhythms and relatively short half-life observed with G-CSF in prior studies with different species is a typical pharmacokinetic behavior of biological molecules. Product clearance follows a first order pharmacokinetics after its subcutaneous and intravenous administration. The elimination half-life is approximately 3.5 hours with a clearance of approximately 0.6 ml/min/kg. The continuous infusion along periods of up to 28 days in patients that recover from autologous bone marrow transplantation is not associated to pharmacological accumulation and elimination half-life are comparable. There is a positive linear correlation between the dose and the serum concentration when administered both by intravenous and subcutaneous route. Serum concentrations remain above 10 ng/ml during 8 to 16 hours after the subcutaneous administration of the recommended dose. The distribution volume in blood is approximately 150 ml/kg.
Pharmacological Actions: Cancer Patients Receiving Myelosuppressive Chemotherapy: Neutropenia and infection are major dose-limiting side effects of chemotherapy. The risk of initial infection and subsequent complications is directly related to the depth and duration of neutropenia. The magnitude of neutropenia is dependent on the intensity of the chemotherapy regimen. Filgrastim has been shown to be safe and effective in accelerating the recovery of neutrophil count following a variety of chemotherapy regimens. The benefits of therapy were shown to be prevention of infection as manifested by febrile neutropenia, decreased hospitalization, and decreased antibiotic usage. No difference in survival or disease progression was demonstrated.
Patients with Acute Myeloid Leukemia Receiving Induction or Consolidation Chemotherapy: Essentially all patients with Acute Myeloid Leukemia receiving induction therapy, and most such patients receiving intensive, post remission consolidation therapy, develop fevers requiring hospitalization and intravenous antibiotics until neutrophil recovery occurs.
Treatment with Filgrastim significantly reduced the median time to Absolute Neutrophils Count (ANC) recovery and the median duration of fever, antibiotic use, and hospitalization following induction chemotherapy. There are no reports of Filgrastim effects related with complete remission rate, disease-free survival, time to progression, or overall survival.
Cancer Patients Receiving Bone Marrow Transplant: The major complications of high-dose chemotherapy supported by autologous Bone Marrow Transplant (BMT) are disease recurrence, infection, the need for red blood cell and platelet transfusions, delayed or incomplete engraftment, organ damage from the ablative regimen, prolonged hospitalization, and the high cost of treatment. These same problems plus graft-versus-host disease and graft rejection are also present in patients undergoing allogeneic BMT. Filgrastim have been administered following both autologous and allogeneic BMT in anticipation of reducing the severity of infectious complications, thereby decreasing hospitalization time, reducing costs, and improving quality of life.
Peripheral Blood Progenitor Cells Collection and Therapy in Cancer Patients: The mobilization of Peripheral Blood Progenitor Cells (PBPC) substitutes the autologous BMT. The major adverse reactions associated with the procedure are reduction in the platelets numbers and other hematopoietic elements. Use of Filgrastim to mobilize PBPC into the circulation for harvesting is expected to enhance progenitor numbers, lessen the frequency, duration, and cost of leukopheresis procedures, potentially speed hematological recovery after transplantation of the CSF-mobilized cells, and reduce the hospitalization.
Patients with Severe Chronic Neutropenia: Severe chronic neutropenia (SCN) (idiopathic, cyclic, and congenital) is characterized by a selective decrease in the number of circulating neutrophils and an enhanced susceptibility to bacterial infections. The administration of Filgrastim has been shown to be safe and effective in causing a sustained increase in the neutrophil count and a decrease in infectious morbidity in treated patients.
Patients with HIV/AIDS: The use of Filgrastim in HIV-infected patients remains the normal number of neutrophils to allow controlled dosage of antivirals and other myelosuppressive medications. There are not evidences that HIV replication increase in HIV-positive patients treated with Filgrastim.
