Filgia

Filgrastim (recombinant human granulocyte colony stimulating factor).

Each mL contains: Filgrastim (Recombinant Human Granulocyte Colony Stimulating Factor) 300 μg.

FILGIA is a medicine containing Filgrastim (Recombinant Human Granulocyte Colony Stimulating Factor) that used to reduce the duration of neutropenia in patients treated with established cytotoxic chemotherapy for non-myeloid malignancy.
Pharmacology: Filgrastim (Recombinant Human Granulocyte Colony Stimulating Factor/rHu G-CSF) is a 175 amino acid protein manufactured by recombinant DNA technology. It is produced by Escherichia coli (E.coli) bacteria into which the human granulocyte colony stimulating factor gene has been inserted. G-CSF is a colony stimulating factor which produced by monocyte, fibroblast, and endothelial cell. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end cell functional activation (including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing, and the increased expression of some functions associated with cell surface antigens).
In patients with various non-myeloid malignancies, Filgrastim administration results in a dose dependent increase in circulating neutrophil counts. In general, neutrophil counts returns to baseline, in most cases within 4 days, when Filgrastim therapy discontinued. The absolute monocyte count is reported to increase in a dose dependent manner inmost patients receiving Filgrastim. However, the percentage of monocytes in the differential count remains within the normal range. Absolute counts of both eosinophils and basophils do not change and are within the normal range following administration of Filgrastim. Increases in lymphocyte counts following Filgrastim administrations have been reported in some normal subjects and cancer patients.
Pharmacokinetics: Filgrastim can be administered intravenously or subcutaneously. A positive linear correlation occurred between the parenteral dose and both the serum concentration and area under the concentration-time curves. Continuous IV infusion with Filgrastim 20 μg/kg body weight resulted in mean serum concentration approximately 48 ng/mL. Subcutaneous administration of 3.45 μg/kg body weight and 11.5 μg/kg body weight resulted in maximum concentration (Cmax) of 4 and 49 ng/mL respectively, within 2 to 8 hours.
The volume of distribution in blood is approximately 150 mL/kg. Half-life for IV and SC administration following doses of 1 μg/kgBW/day are 1.4 hours and 2.15 hours. Filgrastim undergoes extensive renal and hepatic metabolism. Clearance rate depends on neutrophil counts, where elimination half-life decreases from 4.7 to 2 hours with higher neutrophil count. About 94% of administered drug is excreted in urine and 4% in faeces.

For reduction in the duration of neutropenia in patients treated with established cytotoxic chemotherapy for non-myeloid malignancy.

Dosage: Recommended Dose: 5 μg/kg body weight once daily. A CBC and platelet count should be obtained before instituting FILGIA therapy and monitored twice weekly during therapy. FILGIA should be administered daily for up to 2 weeks, until the ANC has reached 10,000/mm³ following the expected chemotherapy-induced neutrophil nadir. The duration of FILGIA therapy needed to attenuate chemotherapy-induced neutropenia may be dependent on the myelosuppressive potential of the chemotherapy regimen employed.
FILGIA therapy should be discontinued if the ANC surpasses 10,000/mm³ after the expected chemotherapy-induced neutrophil nadir.
Administration: FILGIA may be administered as SC bolus injection or as a short IV infusion, diluted in 5% glucose solution, given over 30 minutes. FILGIA should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. FILGIA should not be administered in the period 24 hours before the administration of chemotherapy.
In patients receiving cytotoxic chemotherapy, a transient increase in neutrophil counts is typically seen 1-2 days after initiation of FILGIA therapy. However, for a sustained therapeutic response, FILGIA therapy should not be discontinued before the expected nadir has passed and the neutrophil counts has recovered to the normal range. The required duration of treatment can be up to 14 days, depending on the type, dose and schedule of cytotoxic chemotherapy used.

The effects of Filgrastim over dosage have not been established.

Patients with unknown hypersensitivity to Escherichia coli-derived protein, Filgrastim or its constituents. Patients with myeloid malignancy. Filgrastim should not be used to increase the dose of cytotoxic chemotherapy beyond dosage regimens.

Filgrastim is a growth factor that primarily stimulates neutrophils. However, the possibility that Filgrastim can act as a growth factor for any tumor type cannot be excluded. Therefore, the use of Filgrastim is not recommended in myeloid premalignant and malignant condition.
A white blood cell count should be performed at regular intervals during Filgrastim therapy. If leucocyte counts exceed 50 x 10⁹/L after the expected nadir, Filgrastim should be discontinued immediately.
Monitoring of bone density may be indicated in patients with underlying osteoporotic bone disease who received Filgrastim. Studies have not been performed with Filgrastim in patients with severe impairment of renal or hepatic function and therefore, its use in this patient group cannot be recommended.
The safety of Filgrastim has not been established in children.
Simultaneous use with chemotherapy and radiation therapy: The safety and efficacy of Filgrastim have not been evaluated in patients receiving concurrent cytotoxic chemotherapy. However, because of the potential sensitivity of rapidly dividing myeloid cells to cytotoxic chemotherapy, do not use Filgrastim in the period 24 hours before through 24 hours after the administration of cytotoxic chemotherapy. The safety and efficacy of Filgrastim have not been evaluated in patients receiving concurrent radiation therapy. Simultaneous use of Filgrastim with chemotherapy and radiation therapy should be avoided.
Leukocytosis: In order to avoid the potential complications of excessive leukocytosis, a Complete Blood Count (CBC) is recommended twice per week during therapy of Filgrastim.
Use in Pregnancy and Lactation: The safety of Filgrastim has not been established in pregnant women. In pregnancy, the possible risk of Filgrastim use to the fetus must be weighed against the expected therapeutic benefit. It is not known whether Filgrastim is excreted in human milk, therefore Filgrastim is not recommended for use in nursing woman.

Use in Pregnancy and Lactation: The safety of Filgrastim has not been established in pregnant women. In pregnancy, the possible risk of Filgrastim use to the fetus must be weighed against the expected therapeutic benefit. It is not known whether Filgrastim is excreted in human milk, therefore Filgrastim is not recommended for use in nursing woman.

Mild-moderate musculoskeletal pain during treatment (severe cases occasionally appear), dysuria, thrombocytopenia, splenomegaly, anemia, epistaxis, cephalgia, diarrhea, vasculitis, medullary bone pain, nausea/vomiting, alopecia, neutropenic fever, mucositis, fatigue, anorexia, dyspnea, headache, cough, skin rash, chest pain, stomatitis, constipation, pain (unspecified), and reversible elevation in serum uric acid, lactate dehydrogenase enzyme, alkaline phosphatase, gamma-glutamyl transpeptidase.

Major compatibilities: Filgrastim should not be diluted with saline solutions.
Drug interactions between Filgrastim and other drugs have not been fully evaluated. Drugs which may potentiate the release of neutrophils, such as lithium, should be used with caution.

Store between 2° and 8°C, avoid shaking.
FILGIA can be stored below 25°C maximum 24 hours before injecting.

Haematopoietic Agents / Supportive Care Therapy

L03AA02 - filgrastim ; Belongs to the class of colony stimulating factors. Used as immunostimulants.

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