Cancer patients receiving myelosuppressive chemotherapy: The decrease of the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever.

Cancer patients undergoing Acute Myeloid Leukemia: The reduction of the time to neutrophil recovery and the duration of fever, following induction or consolidation chemotherapy treatment of patients with acute myeloid leukemia (AML).

Cancer Patients Receiving Bone Marrow Transplantation (BMT): The reduction of the duration of neutropenia and neutropenia-related clinical sequelae, e.g., febrile neutropenia, in patients with non-myeloid malignancies undergoing myeloablative chemotherapy followed by bone marrow transplantation.

Patients with severe chronic neutropenia: The reduction of the incidence and duration of sequelae of neutropenia (e.g., fever, infection, or oropharyngeal ulcers) in symptomatic patients with congenital neutropenia, cyclic neutropenia, or idiopathic neutropenia.

Patients acutely exposed to myelosuppressive doses of radiation: The increase of survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic syndrome of acute radiation syndrome).

Patients with HIV infection: The prevention and treatment of persistent neutropenia in patients with advanced HIV infection, in order to reduce the risk of bacterial infections, when other options to manage neutropenia are inappropriate.

Filgrastim is a 175 amino acid human granulocyte colony-stimulating factor (G-CSF) manufactured by recombinant DNA technology. Filgrastim regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation and differentiation. It also causes enhanced phagocytic ability, priming of cellular metabolism associated with respiratory burst, antibody-dependent killing, and increased expression of some cell surface antigens.

Filgrastim exhibits nonlinear pharmacokinetics. Clearance is dependent on Filgrastim concentration and neutrophil count. Filgrastim is cleared by the kidney. It has a tmax of 2 to 8 hours. The absolute bioavailability of Filgrastim after subcutaneous administration is 60-70%.

Cancer patients receiving myelosuppressive chemotherapy or induction and/or consolidation chemotherapy for AML: The recommended dose of Filgrastim is 0.5 MU (5 mcg)/kg/day, administered as a single daily subcutaneous injection or by intravenous infusion (over 30 minutes). The first dose should not be administered less than 24 hours following cytotoxic chemotherapy. Continue until the neutrophil count is in the normal range, usually for 14 days (up to 38 days in AML).

Cancer patients undergoing bone marrow transplantation: The recommended dosage of Filgrastim following bone marrow transplantation (BMT) is 1.0 MU (10 mcg)/kg/day given as an intravenous infusion no longer than 24 hours. Administer the first dose of Filgrastim at least 24 hours after cytotoxic chemotherapy and at least 24 hours after bone marrow transplantation. Dose adjustment should be made according to absolute neutrophil count (ANC).

Patients undergoing autologous peripheral blood progenitor cell (PBPC) collection and therapy: The recommended dosage of Filgrastim for the mobilization of autologous PBPC is 1.0 MU (10 mcg)/kg/day given by subcutaneous injection for 5-7 days. Administer Filgrastim for at least 4 days before the first leukapheresis procedure and continue until the last leukapheresis. Discontinue Filgrastim if the white blood cell (WBC) count rises to greater than 100,000/mm³.

Patients with severe chronic neutropenia: The recommended starting dosage in patients with congenital neutropenia is 0.6 MU (6 mcg)/kg as a twice-daily subcutaneous injection, and in patients with idiopathic or cyclic neutropenia, it is 0.5 MU (5 mcg)/kg as a single daily subcutaneous injection. Dose adjustment should be made according to ANC and complete blood count (CBC).

Patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome): The recommended dose of Filgrastim is 1.0 MU (10 mcg)/kg as a single daily subcutaneous injection for patients exposed to myelosuppressive doses of radiation.

Patients with HIV infection: The recommended starting dose of Filgrastim is 0.1 MU (1.0 mcg)/kg/day given daily by subcutaneous injection, with titration up to a maximum of 0.4 MU (4 mcg)/kg/day until a normal neutrophil count is reached and can be maintained (ANC > 2.0 x 10⁹/L), or as directed by registered physicians.

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.

Filgrastim is contraindicated in patients with a history of serious allergic reactions to human granulocyte colony-stimulating factors such as Filgrastim or peg-Filgrastim, and in patients with severe congenital neutropenia (Kostmann's syndrome).

Most common side effects in patients:

• With non-myeloid malignancies receiving myelosuppressive anti-cancer drugs: pyrexia, pain, rash, cough, and dyspnea.

• With AML: pain, epistaxis, and rash.

• With non-myeloid malignancies undergoing myeloablative chemotherapy followed by BMT: rash.

• Undergoing peripheral blood progenitor cell mobilization and collection: bone pain, pyrexia, and headache.

• With severe chronic neutropenia (SCN): pain, anemia, epistaxis, diarrhea, hypoesthesia, and alopecia.

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised if it is administered to women who are breastfeeding.

• Filgrastim should not be administered within 24 hours before and after chemotherapy.
• The possibility of Filgrastim acting as a growth factor for any tumor type cannot be excluded.
• To avoid adverse effects of excessive neutrophils, a complete blood count is recommended twice per week during treatment.
• Filgrastim is given by subcutaneous or intravenous infusion as required.
• Dilution of Filgrastim concentration less than 5 mcg/ml is not recommended at any time.
• Filgrastim may be diluted in 5% dextrose as required.

The maximum tolerated dose of Filgrastim has not been determined. Patients in the BMT studies received up to 13.8 MU (138 mcg)/kg/day without toxic effects.

Haematopoietic Agents

Refrigerate at 2-8°C. Protect from light. Do not freeze and avoid shaking.