Filgrastim may be given intravenously or subcutaneously. Doses may be expressed in micrograms or in units; 10 micrograms is equivalent to 1 million units.
As an adjunct to antineoplastic therapy, filgrastim is given in a dose of 5 micrograms/kg daily starting not less than 24 hours after the last dose of antineoplastic. It can be given as a single daily subcutaneous injection, as a continuous intravenous or subcutaneous infusion, or as a daily intravenous infusion over 15 to 30 minutes. Treatment is continued until the neutrophil count has stabilised within the normal range which may take up to 14 days or more. A formulation of filgrastim conjugated with monomethoxy polyethylene glycol (pegfilgrastim) may also be used to reduce the incidence of neutropenia associated with antineoplastic therapy; it is given by subcutaneous injection in a single dose of 6 mg, given not less than 24 hours after the last dose of antineoplastic.
The initial dose of filgrastim following bone marrow transplantation is 10 micrograms/kg daily, adjusted according to response. This may be given by intravenous infusion over 30 minutes, intravenous infusion over 4 hours, or by continuous intravenous or subcutaneous infusion over 24 hours.
For mobilisation of peripheral blood progenitor cells, a dose of 10 micrograms/kg daily of filgrastim may be given subcutaneously as a single daily injection or by continuous infusion; if given after myelosuppressive chemotherapy this dose is halved to 5 micrograms/kg daily by subcutaneous injection.
In patients with congenital neutropenia the initial dose is 12 micrograms/kg daily and in patients with idiopathic or cyclic neutropenia the initial dose is 5 micrograms/kg daily. In these forms of neutropenia the dose is given subcutaneously in single or divided doses and should be adjusted according to response.
In patients with HIV infection and persistent neutropenia the initial dose is 1 microgram/kg daily by subcutaneous injection. The dose may be titrated up to a maximum of 4 micrograms/kg daily until a normal neutrophil count is achieved and then adjusted for maintenance according to response. Maintenance doses of 300 micrograms daily on 1 to 7 days a week have been used.
The filgrastim doses described above for patients receiving antineoplastic therapy and for chronic neutropenias may also be given to children.
Since granulocyte colony-stimulating factors such as filgrastim can promote growth of myeloid cells in vitro their use in myeloid malignancies has been contra-indicated, although recently colony-stimulating factors have been used in some patients with myeloid diseases without stimulation of malignant cells. However, caution is required when they are used in patients with any pre-malignant or malignant myeloid condition. They should not be used from 24 hours before until 24 hours after cytotoxic chemotherapy due to the sensitivity of rapidly dividing myeloid cells.
The complete blood count should be monitored regularly during therapy with granulocyte colony-stimulating factors. Treatment should be withdrawn in patients who develop signs of pulmonary infiltrates. Bone density should be monitored in patients with osteoporosis who are receiving long-term treatment with filgrastim.
The main adverse effects of granulocyte colony-stimulating factors such as filgrastim during short-term treatment are musculoskeletal pain and dysuria. Hypersensitivity reactions have been reported rarely. In patients receiving long-term treatment the most frequent adverse effects are bone pain and musculoskeletal pain. Other side-effects include splenic enlargement, thrombocytopenia, anaemia, epistaxis, headache, diarrhoea, and cutaneous vasculitis. There have been reports of pulmonary infiltrates leading to respiratory failure or acute respiratory distress syndrome.
Preparations of filgrastim may contain sorbitol as an excipient; care is advisable in patients with hereditary fructose intolerance.
Colony-stimulating factors are fetotoxic in animal studies.